When to start — Early institution of treatment for diabetes, at a time when the A1C is not substantially elevated, is associated with improved glycemic management over time and decreased long-term complications [ 46 ]. Pharmacologic therapy should be initiated along with consultation for lifestyle modification focusing on dietary and other lifestyle contributors to hyperglycemia.

Weight loss and weight loss maintenance underpins all effective type 2 diabetes therapy, and lifestyle change reduces the risk of weight gain associated with sulfonylureas and insulin. However, for those patients who have clear and modifiable contributors to hyperglycemia and who are motivated to change them eg, commitment to reduce consumption of sugar-sweetened beverages , a three-month trial of lifestyle modification prior to initiation of pharmacologic therapy is warranted.

Choice of initial therapy — Our suggestions are based upon clinical trial evidence and clinical experience in achieving glycemic targets and minimizing adverse effects table 1 , with the recognition that there is a paucity of high-quality, head-to-head drug comparison trials and long-duration trials or ones with important clinical endpoints, such as effects on complications.

The long-term benefits and risks of using one approach over another are unknown. In selecting initial therapy, we consider patient presentation eg, presence or absence of symptoms of hyperglycemia, comorbidities, baseline A1C level , individualized treatment goals and preferences, the glucose-lowering efficacy of individual drugs, and their adverse effect profile, tolerability, and cost [ 47 ].

We prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed, rather than starting with combination therapy [ 48 ]. Related Pathway s : Diabetes: Initial therapy for non-pregnant adults with type 2 DM.

Asymptomatic, not catabolic — The majority of patients with newly diagnosed type 2 diabetes are asymptomatic, without symptoms of catabolism eg, without polyuria, polydipsia, or unintentional weight loss. Hyperglycemia may be noted on routine laboratory examination or detected by screening.

Metformin — In the absence of specific contraindications, we suggest metformin as initial therapy for patients with newly diagnosed type 2 diabetes who are asymptomatic.

We begin with mg once daily with the evening meal and, if tolerated, add a second mg dose with breakfast. The dose can be increased slowly one tablet every one to two weeks as tolerated to reach a total dose of mg per day.

See 'When to start' above and "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Dosing'. Metformin is the preferred initial therapy because of glycemic efficacy see 'Glycemic efficacy' below , promotion of modest weight loss, very low incidence of hypoglycemia, general tolerability, and favorable cost [ 47 ].

Metformin does not have adverse cardiovascular effects, and it appears to decrease cardiovascular events [ ]. See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Metformin is far less expensive and has more clinical practice experience than glucagon-like peptide 1 GLP-1 receptor agonists and sodium-glucose cotransporter 2 SGLT2 inhibitors. Although some guidelines and experts endorse the initial use of these alternative agents as monotherapy or in combination with metformin [ 48,52 ], we prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed, rather than starting with combination therapy.

In the clinical trials that demonstrated the protective effects of GLP-1 receptor agonists and SGLT2 inhibitors, these agents were added to background metformin therapy in most participants. Further, the cardiorenal benefits of GLP-1 receptor agonists and SGLT2 inhibitors have not been demonstrated in drug-naïve patients without established CVD or at low cardiovascular risk or without severely increased albuminuria.

Although each diabetes medication is associated with adverse events, metformin is associated with less weight gain and fewer episodes of hypoglycemia compared with sulfonylureas, and with less edema, heart failure HF , and weight gain compared with thiazolidinediones.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Although virtually all recommendations for initial pharmacologic therapy outside of China, where alpha-glucosidase inhibitors are recommended as an alternate first-line monotherapy [ 53 ] endorse use of metformin , there are, in fact, relatively few relevant direct comparative effectiveness data available.

Contraindications to or intolerance of metformin — For patients who have gastrointestinal intolerance of metformin , slower titration, ensuring that the patient is taking the medication with food, or switching to an extended-release formulation may improve tolerability.

For patients who still cannot tolerate metformin or have contraindications to it, we choose an alternative glucose-lowering medication guided initially by patient comorbidities, and in particular, the presence of atherosclerotic CVD ASCVD or albuminuric chronic kidney disease.

See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'. When compared with placebo, the GLP-1 receptor agonists liraglutide , semaglutide , and dulaglutide demonstrated favorable atherosclerotic cardiovascular and kidney outcomes [ ].

The SGLT2 inhibitors empagliflozin , canagliflozin , and dapagliflozin have also demonstrated benefit, especially for HF hospitalization, risk of kidney disease progression, and mortality [ ]. Patients at high CVD risk but without a prior event might benefit, but the data are less supportive.

Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria. To select a medication, we use shared decision-making with a focus on beneficial and adverse effects within the context of the degree of hyperglycemia as well as a patient's comorbidities and preferences.

As examples:. SGLT2 inhibitors with cardiovascular benefit empagliflozin or canagliflozin are good alternatives, especially in the presence of HF.

Given the high cost of these classes of medications, formulary coverage often determines the choice of the first medication within the class. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.

Choice of agent is primarily dictated by provider preference, insurance formulary restrictions, eGFR, and cost. In the setting of declining eGFR, the main reason to prescribe SGLT2 inhibitors is to reduce progression of DKD. However, kidney and cardiac benefits have been shown in patients with eGFR below this threshold.

Dosing in the setting of DKD is reviewed in detail elsewhere. See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'. An alternative or an additional agent may be necessary to achieve glycemic goals.

GLP-1 receptor agonists are an alternative in patients with DKD as their glycemic effect is not related to eGFR. In addition, GLP-1 receptor agonists have been shown to slow the rate of decline in eGFR and prevent worsening of albuminuria. See 'Microvascular outcomes' below and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

Of note, we avoid use of SGLT2 inhibitors in patients with frequent bacterial urinary tract infections or genitourinary yeast infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol abuse disorder because of increased risk while using these agents.

SLGT2 inhibitors should be held for 3 to 4 days before procedures including colonoscopy preparation and with poor oral intake to prevent diabetic ketoacidosis. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'.

Repaglinide acts at the sulfonylurea receptor to increase insulin secretion but is much shorter acting than sulfonylureas and is principally metabolized by the liver, with less than 10 percent renally excreted. Limited data suggest that dipeptidyl peptidase 4 DPP-4 inhibitors are effective and relatively safe in patients with chronic kidney disease.

However, linagliptin is the only DPP-4 inhibitor that does not require a dose adjustment in the setting of kidney failure. GLP-1 receptor agonists may also be used safely in chronic kidney disease stage 4, but patient education for signs and symptoms of dehydration due to nausea or satiety is warranted to reduce the risk of acute kidney injury.

Insulin may also be used, with a greater portion of the total daily dose administered during the day due to the risk of hypoglycemia, especially overnight, in chronic kidney disease and end-stage kidney disease ESKD.

See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Patients not on dialysis'.

Without established cardiovascular or kidney disease — For patients without established CVD or kidney disease who cannot take metformin , many other options for initial therapy are available table 1.

We suggest choosing an alternative glucose-lowering medication guided by efficacy, patient comorbidities, preferences, and cost. Although historically insulin has been used for type 2 diabetes only when inadequate glycemic management persists despite oral agents and lifestyle intervention, there are increasing data to support using insulin earlier and more aggressively in type 2 diabetes.

By inducing near normoglycemia with intensive insulin therapy, both endogenous insulin secretion and insulin sensitivity improve; this results in better glycemic management, which can then be maintained with diet, exercise, and oral hypoglycemics for many months thereafter.

Insulin may cause weight gain and hypoglycemia. See "Insulin therapy in type 2 diabetes mellitus", section on 'Indications for insulin'.

If type 1 diabetes has been excluded, a GLP-1 receptor agonist is a reasonable alternative to insulin [ 66,67 ].

The frequency of injections and proved beneficial effects in the setting of CVD are the major differences among the many available GLP-1 receptor agonists. In practice, given the high cost of this class of medications, formulary coverage often determines the choice of the first medication within the class.

Cost and insurance coverage may limit accessibility and adherence. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Patient selection'.

Each one of these choices has individual advantages, benefits, and risks table 1. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Patient selection' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Potential indications'.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Weight loss' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Weight loss'.

The choice of sulfonylurea balances glucose-lowering efficacy, universal availability, and low cost with risk of hypoglycemia and weight gain. Pioglitazone , which is generic and another relatively low-cost oral agent, may also be considered in patients with specific contraindications to metformin and sulfonylureas.

However, the risk of weight gain, HF, fractures, and the potential increased risk of bladder cancer raise the concern that the overall risks and cost of pioglitazone may approach or exceed its benefits. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Potential indications'.

For patients who are starting sulfonylureas, we suggest initiating lifestyle intervention first, at the time of diagnosis, since the weight gain that often accompanies a sulfonylurea will presumably be less if lifestyle efforts are underway.

However, if lifestyle intervention has not produced a significant reduction in symptoms of hyperglycemia or in glucose values after one or two weeks, then the sulfonylurea should be added.

Side effects may be minimized with diabetes self-management education focusing on medication reduction or omission with changes in diet, food accessibility, or activity that may increase the risk of hypoglycemia.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Suggested approach to the use of GLP-1 receptor agonist-based therapies' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Mechanism of action' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Mechanism of action' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia'.

Symptomatic catabolic or severe hyperglycemia — The frequency of symptomatic or severe diabetes has been decreasing in parallel with improved efforts to diagnose diabetes earlier through screening.

If patients have been drinking a substantial quantity of sugar-sweetened beverages, reduction of carbohydrate intake, and rehydration with sugar-free fluids will help to reduce glucose levels within several days.

See "Insulin therapy in type 2 diabetes mellitus", section on 'Initial treatment'. However, for patients who are injection averse, initial therapy with high-dose sulfonylurea is an alternative option. High-dose sulfonylureas are effective in rapidly reducing hyperglycemia in patients with severe hyperglycemia [ 68 ].

Metformin monotherapy is not helpful in improving symptoms in this setting, because the initial dose is low and increased over several weeks.

However, metformin can be started at the same time as the sulfonylurea, slowly titrating the dose upward. Once the diet has been adequately modified and the metformin dose increased, the dose of sulfonylurea can be reduced and potentially discontinued.

Patients with type 2 diabetes require relatively high doses of insulin compared with those needed for type 1 diabetes.

Insulin preparations, insulin regimens, and timing of dosing are discussed in detail elsewhere. See "Insulin therapy in type 2 diabetes mellitus". See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Administration'. We typically use glimepiride 4 or 8 mg once daily.

An alternative option is immediate-release glipizide 10 mg twice daily or, where available, gliclazide immediate-release 80 mg daily.

We contact the patient every few days after initiating therapy to make dose adjustments increase dose if hyperglycemia does not improve or decrease dose if hyperglycemia resolves quickly or hypoglycemia develops. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Sulfonylureas'.

Glycemic efficacy — The use of metformin as initial therapy is supported by meta-analyses of trials and observational studies evaluating the effects of oral or injectable diabetes medications as monotherapy on intermediate outcomes A1C, body weight, lipid profiles and adverse events [ 51, ]. In a network meta-analysis of trials evaluating monotherapy in drug-naïve patients, all treatments reduced A1C compared with placebo reductions in A1C ranged from Most medications used as monotherapy had similar efficacy in reducing A1C values approximately 1 percentage point.

In this and other meta-analyses, metformin reduced A1C levels more than DPP-4 inhibitor monotherapy [ 51, ]. There are few high-quality, head-to-head comparison trials of the available oral agents.

In one such trial, A Diabetes Outcome Progression Trial ADOPT , recently diagnosed patients with type 2 diabetes were randomly assigned to monotherapy with the thiazolidinedione rosiglitazone , metformin , or glyburide [ 72 ].

At the four-year evaluation, 40 percent of the subjects in the rosiglitazone group had an A1C value less than 7 percent, as compared with 36 percent in the metformin group and 26 percent in the glyburide group. Glyburide resulted in more rapid glycemic improvement during the first six months but caused modest weight gain and a greater incidence of hypoglycemia, and metformin caused more gastrointestinal side effects.

Rosiglitazone caused greater increases in weight, peripheral edema, and concentrations of low-density lipoprotein LDL cholesterol. There was also an unexpected increase in fractures in women taking rosiglitazone.

The study was limited by a high rate of withdrawal of study participants. Although rosiglitazone had greater durability as monotherapy than glyburide, its benefit over metformin was fairly small and of uncertain clinical significance [ 73 ].

See "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety'. Cardiovascular outcomes — Cardiovascular benefit has been demonstrated for selected classes of diabetes medications, usually when added to metformin.

See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Monotherapy failure'. The cardiovascular effects of diabetes drugs are reviewed in the individual topics. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus".

In trials of patients with type 2 diabetes with and without chronic kidney disease, GLP-1 receptor agonists slowed the rate of decline in eGFR and prevented worsening of albuminuria [ 54,56,58 ].

These trials and other trials evaluating microvascular outcomes are reviewed in the individual topics. Guidelines — Our approach is largely consistent with American and European guidelines [ 52,74,75 ].

A consensus statement regarding the management of hyperglycemia in type 2 diabetes by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD was developed in and has been updated regularly, with the most recent revision published in [ 75 ].

The guidelines emphasize the importance of individualizing the choice of medications for the treatment of diabetes, considering important comorbidities CVD, HF, or chronic kidney disease; hypoglycemia risk; and need for weight loss and patient-specific factors including patient preferences, values, and cost [ 75 ].

We also agree with the World Health Organization WHO that sulfonylureas have a long-term safety profile, are inexpensive, and are highly effective, especially when used as described above, with patient education and dose adjustment to minimize side effects [ 76 ]. Blood glucose monitoring BGM is not necessary for most patients with type 2 diabetes who are on a stable regimen of diet or oral agents and who are not experiencing hypoglycemia.

BGM may be useful for some patients with type 2 diabetes who use the results to modify eating patterns, exercise, or insulin doses on a regular basis. See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Type 2 diabetes'. The balance among efficacy in lowering A1C, side effects, and costs must be carefully weighed in considering which drugs or combinations to choose.

Avoiding insulin, the most potent of all hypoglycemic medications, at the expense of poorer glucose management and greater side effects and cost, is not likely to benefit the patient in the long term. See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Our approach'.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Diabetic kidney disease".

These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic.

We encourage you to print or e-mail these topics to your patients. You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest. Weight reduction through diet, exercise, and behavioral modification can all be used to improve glycemic management, although the majority of patients with type 2 diabetes will require medication.

See 'Diabetes education' above. Glycemic targets are generally set somewhat higher for older adults and for those with comorbidities or a limited life expectancy and little likelihood of benefit from intensive therapy. See 'Glycemic management' above and "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Choosing a glycemic target'.

In the absence of specific contraindications, we suggest metformin as initial therapy for most patients Grade 2B. Although some guidelines and experts endorse the initial use of alternative agents as monotherapy or in combination with metformin, we prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed.

See 'Metformin' above and 'Glycemic efficacy' above. We suggest initiating metformin at the time of diabetes diagnosis Grade 2C , along with consultation for lifestyle intervention. See 'When to start' above.

The dose of metformin should be titrated to its maximally effective dose usually mg per day in divided doses over one to two months, as tolerated. See 'Contraindications to or intolerance of metformin' above.

See 'Established cardiovascular or kidney disease' above. The majority of patients in the cardiovascular and renal outcomes trials had established cardiovascular disease CVD or diabetic kidney disease DKD with severely increased albuminuria, and therefore, these are the primary indications for one of these drugs.

See 'Without established cardiovascular or kidney disease' above. Each one of these choices has individual advantages and risks table 1. Choice of medication is guided by efficacy, patient comorbidities, preferences, and cost. Sulfonylureas remain a highly effective treatment for hyperglycemia, particularly when cost is a barrier.

Side effects of hypoglycemia and weight gain can be mitigated with careful dosing and diabetes self-management education. For patients who are injection averse, initial therapy with high-dose sulfonylurea is an alternative, particularly for patients who have been consuming large amounts of sugar-sweetened beverages, in whom elimination of carbohydrates can be anticipated to cause a reduction in glucose within several days.

See 'Symptomatic catabolic or severe hyperglycemia' above and "Insulin therapy in type 2 diabetes mellitus". Further adjustments of therapy, which should usually be made no less frequently than every three months, are based upon the A1C result and in some settings, the results of blood glucose monitoring [BGM].

See 'Monitoring' above. See "Management of persistent hyperglycemia in type 2 diabetes mellitus" and "Insulin therapy in type 2 diabetes mellitus". Why UpToDate?

Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you. Select the option that best describes you. View Topic. Font Size Small Normal Large. Initial management of hyperglycemia in adults with type 2 diabetes mellitus.

Formulary drug information for this topic. No drug references linked in this topic. Find in topic Formulary Print Share.

View in. Language Chinese English. Author: Deborah J Wexler, MD, MSc Section Editor: David M Nathan, MD Deputy Editor: Katya Rubinow, MD Contributor Disclosures.

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan This topic last updated: Dec 23, TREATMENT GOALS Glycemic management — Target glycated hemoglobin A1C levels in patients with type 2 diabetes should be tailored to the individual, balancing the anticipated reduction in microvascular complications over time with the immediate risks of hypoglycemia and other adverse effects of therapy.

Summary of glucose-lowering interventions. UK Prospective Diabetes Study UKPDS Group. Lancet ; Holman RR, Paul SK, Bethel MA, et al. N Engl J Med ; Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.

ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes.

Rawshani A, Rawshani A, Franzén S, et al. Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.

Kazemian P, Shebl FM, McCann N, et al. Evaluation of the Cascade of Diabetes Care in the United States, JAMA Intern Med ; Pal K, Eastwood SV, Michie S, et al.

Computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev ; :CD Saffari M, Ghanizadeh G, Koenig HG. Health education via mobile text messaging for glycemic control in adults with type 2 diabetes: a systematic review and meta-analysis.

Prim Care Diabetes ; Liang X, Wang Q, Yang X, et al. Effect of mobile phone intervention for diabetes on glycaemic control: a meta-analysis. Diabet Med ; Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus.

J Clin Endocrinol Metab ; Utzschneider KM, Carr DB, Barsness SM, et al. Diet-induced weight loss is associated with an improvement in beta-cell function in older men. Wing RR, Blair EH, Bononi P, et al.

Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients.

Diabetes Care ; Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes DiRECT : an open-label, cluster-randomised trial.

Delahanty LM. The look AHEAD study: implications for clinical practice go beyond the headlines. J Acad Nutr Diet ; Evert AB, Dennison M, Gardner CD, et al. Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report.

Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial.

Lancet Diabetes Endocrinol ; Niskanen LK, Uusitupa MI, Sarlund H, et al. Five-year follow-up study on plasma insulin levels in newly diagnosed NIDDM patients and nondiabetic subjects. Norris SL, Zhang X, Avenell A, et al. Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type 2 diabetes: a meta-analysis.

Am J Med ; United Kingdom Prospective Diabetes Study UKPDS. Generalized linear mixed models enabled us to see heterogeneity between patients. The marginal quasi-likelihood method was used to estimate the model parameters.

The complete likelihood for all observed data is formulated as The likelihood function has no general closed-form, and integrating over random effects is usually extremely computationally intensive.

In addition to numerically approximating this, integral, methods motivated by Laplace approximation have been proposed To build the generalized linear mixed model analysis, using the procedure we followed, first, we did a bivariable analysis for each of the explanatory variables and based on statistical significance at 0.

We used Akaike and Bayesian information criteria to select the appropriate generalized linear mixed model with its best covariance structure, and the model with the smallest AIC or BIC was considered the best fit 38 , The data sets analyzed in this study are available from the corresponding author on reasonable request.

Diabetes Prevalence in and Projections to and 20—79 years IDF DIABETES ATLAS, Cefalu, W. et al. Classification and diagnosis of diabetes: Standards of medical care in diabetes Diabetes Care 42 , S13—S28 Article Google Scholar. IDF Africa Members - International Diabetes Federation Reaven, P.

Intensive glucose control in patients with type 2 diabetes—year follow-up. Article CAS PubMed PubMed Central Google Scholar. Nigussie, S. Rate of glycemic control and associated factors among type two diabetes mellitus patients in Ethiopia: A cross sectional study.

PLoS ONE 16 5 , e Yosef, T. Poor glycemic control and its contributing factors among type 2 diabetes patients at Adama Hospital Medical College in East Ethiopia. Diabetes Metab. Article PubMed PubMed Central Google Scholar. Demoz, G.

Predictors of poor glycemic control among patients with type 2 diabetes on follow-up care at a tertiary healthcare setting in Ethiopia.

Notes 12 1 , 1—7 Article CAS Google Scholar. Feleke, B. Glycemic control of diabetes mellitus patients in referral hospitals of Amhara Region, Ethiopia: A cross-sectional study.

BioMed Res. Shita, N. Predictors of blood glucose change and vascular complication of type 2 diabetes mellitus patients in Felege Hiwot Referral Hospital, North West Ethiopia. Article ADS Google Scholar.

Andargie, A. A longitudinal data analysis on risk factors for developing type-2 diabetes mellitus at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. Public Health Epidemiol.

Aniley, T. A semi-parametric mixed models for longitudinally measured fasting blood sugar level of adult diabetic patients.

BMC Med. Lozovey, N. Glycemic control rate in type 2 diabetes mellitus patients at a public referral hospital in Rio de Janeiro, Brazil: demographic and clinical factors. Woldu, M. Factors associated with poor glycemic control among patients with type 2 diabetes mellitus in Ambo Hospital, Ambo; Ethiopia.

Google Scholar. Mohammadi, S. Knowledge, attitude and practices on diabetes among type 2 diabetic patients in Iran: a cross-sectional study.

Science 3 4 , — Lumanlan, D. Knowledge, attitudes and practices and its association with glycemic control among type 2 diabetes mellitus patients in a tertiary hospital. Diabetes Res. Al-Rasheedi, A. Glycemic control among patients with type 2 diabetes mellitus in countries of Arabic Gulf.

Health Sci. Badedi, M. Factors associated with long-term control of type 2 diabetes mellitus. The role of educational level in glycemic control among patients with type II diabetes mellitus.

Khan, A. Factors contributing to non-compliance among diabetics attending primary health centers in the Al Hasa district of Saudi Arabia.

Community Med. Al-Kaabi, J. Assessment of dietary practice among diabetic patients in the United Arab Emirates. Diabetic Stud.

Al-Ibrahim, A. Factors Associated with Compliance to Diabetes Self-care Behaviors and Glycemic Control Among Kuwaiti People with Type 2 Diabetes University of Maryland, Fseha, B. Abebe, S. Level of sustained glycemic control and associated factors among patients with diabetes mellitus in Ethiopia: a hospital-based cross-sectional study.

Fiseha, T. Factors associated with glycemic control among diabetic adult out-patients in Northeast Ethiopia. Notes 11 1 , 1—6 Supiyev, A. Diabetes prevalence, awareness and treatment and their correlates in older persons in urban and rural population in the Astana region, Kazakhstan.

Article PubMed Google Scholar. Borgharkar, S. Real-world evidence of glycemic control among patients with type 2 diabetes mellitus in India: The TIGHT study. BMJ Open Diabetes Res. Care 7 1 , e Laiteerapong, N. Diabetes Care 42 3 , — Article CAS PubMed Google Scholar.

Afroz, A. Macro-and micro-vascular complications and their determinants among people with type 2 diabetes in Bangladesh. de Oliveira, R. Glycemic control in elderly people with type 2 diabetes mellitus attending primary health care units. Care Diabetes 15 , — Ismail, M. Prevalence of depression and predictors of glycemic control among type 2 diabetes mellitus patients at family medicine clinic, Suez Canal University Hospital Egypt.

Middle East J. Wang, J. Status of glycosylated hemoglobin and prediction of glycemic control among patients with insulin-treated type 2 diabetes in North China: a multicenter observational study. MacKenzie, J. Role of Anti-hypertension Class Drugs in the Pathogenesis of Diabetes Mellitus Complications Boston University, American Diabetes Association.

Glycemic targets: Standards of medical care in diabetes Diabetes Care 43 S1 , S66—S Classification and diagnosis of diabetes: standards of medical care in diabetes— ADA Diabetes Care J. Pawitan, Y. In All Likelihood: Statistical Modelling and Inference Using Likelihood Oxford University Press, MATH Google Scholar.

Breslow, N. Approximate inference in generalized linear mixed models. Hosmer, D. Applied Survival Analysis: Time-to-Even Wiley-Interscience, Akaike, H.

A new look at the statistical model identification. IEEE Trans. Control 19 6 , — Article ADS MathSciNet MATH Google Scholar.

Schwarz, G. Estimating the dimension of a model. Article MathSciNet MATH Google Scholar. Download references. We would like to greatly acknowledge Debre Markos and Felege Hiwot Referral Hospital for allowing us to use the T2DM Patient data. Debre Markous University is gratefully acknowledged for financially supporting this work.

Department of Statistics, Debre Markos University, Debre Markos, Ethiopia. You can also search for this author in PubMed Google Scholar. conceived the study, formulated the design, drafted the manuscript, analyzed, and interpreted the data. participated in the conception of the study and revised the manuscript critically for important intellectual content.

All authors have read and approved the manuscript for submission. Correspondence to Nigusie Gashaye Shita. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Reprints and permissions. Glycemic control and its associated factors in type 2 diabetes patients at Felege Hiwot and Debre Markos Referral Hospitals.

Sci Rep 12 , Download citation. Received : 13 January Accepted : 26 May Published : 08 June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects Risk factors Scientific data Statistics.

Abstract Poor glycemic control is a main public health problem among type 2 diabetes mellitus T2DM patients and a significant cause of the development of diabetic complications. Introduction Type 2 diabetes mellitus T2DM is a chronic disease.

Results Characteristics of study participants A total of T2DM patients with observations were included in the analysis. Table 1 Population characteristics for type 2 DM patients with glycimic control stataus observations at Felege Hiwot and Debre Markos Referral Hospital, December January Full size table.

Table 2 Cross tabulation and Univariate analysis of glycemic control status for patients with glycimic control status observations at DMRH and FHRH, December —January Figure 1. Full size image. Table 3 Results of Generalized Linear Mixed model with logit link for factors associated with glycemic control for type 2 diabetes mellitus patients with glycimic control status observations.

Discussion In this study, a generalized linear mixed model with autoregressive order one analysis was used to identify the determinant factors that affected good glycemic control among T2DM patients in two of the major hospitals in North West Ethiopia. Conclusions and recommendations This study revealed that the overall prevalence of poor glycemic control was high at Debre Markos and Felege Hiwot Referral Hospital.

Methods Study design, study area, and study period An institutional-based retrospective follow-up study design was conducted at Felege-Hiwot and Debre Markos Referral Hospital with type 2 diabetes mellitus patients who were enrolled from December to December Source and study population The source population was all T2DM patients who were found at Felege-Hiwot and Debre Markos Referral Hospitals, whereas the study population was all type 2 diabetic patients aged 18 years or older who came to the hospital for diagnosis and follow-up from December to December Inclusion and exclusion criteria T2DM patients with three fasting blood glucose measurements within three months and above the age of 18 years were included in the study, whereas the patient chart would not be available during the data collection period and patients with missing key predictor variables were excluded from the study.

Figure 2. Summary of study participants recruiting flow chart. Table 4 Summarized value of Information criteria for type 2 diabetes mellitus patients with glycimic control status observations at DMRH and FHRH, December —December Data availability The data sets analyzed in this study are available from the corresponding author on reasonable request.

Abbreviations ADA: America Diabetes Association AIC: Akaike information criteria AOR: Adjusted odds ratio BIC: Bayesian information criteria CHD: Coronary heart disease CI: Confidence interval COR: Crude odds ratio DBP: Diastolic Blood pressure DM: Diabetes Mellitus DMRH: Debre Markos Referral Hospital FHRH: Felege-Hiwot Referral Hospital GLMM: Generalized linear mixed model IDF: International Diabetes Federation PAD: Peripheral arterial disease SBP: Systolic Blood pressure T2DM: Type 2 Diabetes Mellitus.

References IDF.

Pharmacologic therapy — Pharmacotherapy targeted solely for weight management is effective in patients with type 2 diabetes. Although metformin is usually started for the management of hyperglycemia, it is also frequently an effective medication to promote modest weight loss.

When additional body weight reduction is a primary goal of therapy, we choose medications that promote weight loss and lower glucose. Glucagon-like peptide 1 GLP-1 receptor and dual GLP-1 and glucose-dependent insulinotropic polypeptide GIP agonist therapies promote weight loss and help prevent weight gain due to other glucose-lowering pharmacotherapies.

We add these medications sequentially to metformin if additional glucose lowering or weight loss is a treatment goal. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus" and "Obesity in adults: Drug therapy". Surgical therapy — Weight loss surgery in patients with obesity and type 2 diabetes results in the largest degree of sustained weight loss and, in parallel, improvements in blood glucose management and the most frequent sustained remissions of diabetes.

Weight loss surgery is an option to treat poorly managed type 2 diabetes when other modalities have failed. This topic is reviewed in detail separately. See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Bariatric metabolic surgery'.

Exercise — Regular exercise is beneficial in type 2 diabetes, independent of weight loss. It leads to improved glycemic management due to increased responsiveness to insulin; it can also delay the progression of impaired glucose tolerance to overt diabetes [ 22,23 ].

These beneficial effects are directly due to exercise, but concurrent weight reduction plays a contributory role.

In one study, however, only 50 percent of patients with type 2 diabetes were able to maintain a regular exercise regimen [ 24 ]. See "Exercise guidance in adults with diabetes mellitus".

Shorter-duration, intensive exercise may be appropriate for physically fit individuals [ 25 ]. Resistance training may be particularly important for individuals with type 2 diabetes who do not have overweight or obesity, in whom relative sarcopenia may contribute to diabetes pathophysiology [ 26 ].

Intensive lifestyle modification — In patients with established type 2 diabetes, intensive behavioral modification interventions focusing on weight reduction and increasing activity levels are successful in reducing weight and improving glycemic management while, at the same time, reducing the need for glucose-lowering and other medications [ 15,18, ].

The intensive intervention included caloric restriction maximum 30 percent calories from fat, minimum 15 percent protein, and the remainder from carbohydrates, in the form of liquid meal replacements, frozen food entrees, or structured meal plans , moderate-intensity physical activity goal minutes weekly , and weekly group or individual sessions with registered dietitians, behavioral psychologists, and exercise specialists.

The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for angina. Although the anticipated follow-up period was After a median follow-up of 9.

The improvement in weight and glycemia did not reduce the occurrence of cardiovascular events. Possible reasons for this finding include the lower-than-expected rates of cardiovascular events in both groups, improved overall cardiovascular risk factor treatment with medical therapy antihypertensives, statins in the standard diabetes education arm, enrollment of a relatively healthy patient population, gradual weight loss in the control group such that the differential weight loss between the two groups was only 2.

A sustained weight loss of greater than that achieved in the trial may be required to reduce the risk of CVD. In an observational post hoc analysis of the Look AHEAD trial, weight loss of 10 percent or greater in the first year was associated with a reduction in the primary outcome 1.

However, this post hoc analysis is problematic. Moreover, the degree of weight loss is difficult to achieve and maintain through lifestyle intervention alone. Weight loss, weight loss maintenance, and exercise remain important components of diabetes management due to overall health benefits.

The following summarizes several other major observations from the Look AHEAD trial [ 27,31, ]:. The difference was attenuated but remained significant throughout the trial 6 versus 3. Changes in waist circumference and physical fitness were also significantly better in the intervention group throughout the study.

By study end, mean A1C was significantly lower in the intervention group 7. Psychological interventions — Patients with type 2 diabetes often experience significant stress, a condition often called diabetes distress, related to the many self-care responsibilities required for glycemic management lifestyle modifications, medication, and blood glucose monitoring [BGM] [ 42 ].

Concurrent depression similarly may interfere with self-care. See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Comorbid conditions'. Psychotherapy reduces psychological distress and improves glycemic management in some [ 43,44 ], but not all [ 45 ], studies.

In a meta-analysis of 12 trials of patients with type 2 diabetes randomly assigned to psychological intervention or usual care, mean A1C was lower in the intervention group pooled mean difference Measures of psychological distress were also significantly lower in the intervention group, but there were no differences in weight management.

Pregnancy planning — All women of childbearing age with diabetes should be counseled about the potential effects of diabetes and commonly used medications on maternal and fetal outcomes and the potential impact of pregnancy on their diabetes management and any existing complications.

See "Pregestational preexisting diabetes: Preconception counseling, evaluation, and management". When to start — Early institution of treatment for diabetes, at a time when the A1C is not substantially elevated, is associated with improved glycemic management over time and decreased long-term complications [ 46 ].

Pharmacologic therapy should be initiated along with consultation for lifestyle modification focusing on dietary and other lifestyle contributors to hyperglycemia. Weight loss and weight loss maintenance underpins all effective type 2 diabetes therapy, and lifestyle change reduces the risk of weight gain associated with sulfonylureas and insulin.

However, for those patients who have clear and modifiable contributors to hyperglycemia and who are motivated to change them eg, commitment to reduce consumption of sugar-sweetened beverages , a three-month trial of lifestyle modification prior to initiation of pharmacologic therapy is warranted.

Choice of initial therapy — Our suggestions are based upon clinical trial evidence and clinical experience in achieving glycemic targets and minimizing adverse effects table 1 , with the recognition that there is a paucity of high-quality, head-to-head drug comparison trials and long-duration trials or ones with important clinical endpoints, such as effects on complications.

The long-term benefits and risks of using one approach over another are unknown. In selecting initial therapy, we consider patient presentation eg, presence or absence of symptoms of hyperglycemia, comorbidities, baseline A1C level , individualized treatment goals and preferences, the glucose-lowering efficacy of individual drugs, and their adverse effect profile, tolerability, and cost [ 47 ].

We prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed, rather than starting with combination therapy [ 48 ]. Related Pathway s : Diabetes: Initial therapy for non-pregnant adults with type 2 DM.

Asymptomatic, not catabolic — The majority of patients with newly diagnosed type 2 diabetes are asymptomatic, without symptoms of catabolism eg, without polyuria, polydipsia, or unintentional weight loss.

Hyperglycemia may be noted on routine laboratory examination or detected by screening. Metformin — In the absence of specific contraindications, we suggest metformin as initial therapy for patients with newly diagnosed type 2 diabetes who are asymptomatic.

We begin with mg once daily with the evening meal and, if tolerated, add a second mg dose with breakfast. The dose can be increased slowly one tablet every one to two weeks as tolerated to reach a total dose of mg per day.

See 'When to start' above and "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Dosing'. Metformin is the preferred initial therapy because of glycemic efficacy see 'Glycemic efficacy' below , promotion of modest weight loss, very low incidence of hypoglycemia, general tolerability, and favorable cost [ 47 ].

Metformin does not have adverse cardiovascular effects, and it appears to decrease cardiovascular events [ ]. See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Metformin is far less expensive and has more clinical practice experience than glucagon-like peptide 1 GLP-1 receptor agonists and sodium-glucose cotransporter 2 SGLT2 inhibitors. Although some guidelines and experts endorse the initial use of these alternative agents as monotherapy or in combination with metformin [ 48,52 ], we prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed, rather than starting with combination therapy.

In the clinical trials that demonstrated the protective effects of GLP-1 receptor agonists and SGLT2 inhibitors, these agents were added to background metformin therapy in most participants.

Further, the cardiorenal benefits of GLP-1 receptor agonists and SGLT2 inhibitors have not been demonstrated in drug-naïve patients without established CVD or at low cardiovascular risk or without severely increased albuminuria.

Although each diabetes medication is associated with adverse events, metformin is associated with less weight gain and fewer episodes of hypoglycemia compared with sulfonylureas, and with less edema, heart failure HF , and weight gain compared with thiazolidinediones.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Although virtually all recommendations for initial pharmacologic therapy outside of China, where alpha-glucosidase inhibitors are recommended as an alternate first-line monotherapy [ 53 ] endorse use of metformin , there are, in fact, relatively few relevant direct comparative effectiveness data available.

Contraindications to or intolerance of metformin — For patients who have gastrointestinal intolerance of metformin , slower titration, ensuring that the patient is taking the medication with food, or switching to an extended-release formulation may improve tolerability.

For patients who still cannot tolerate metformin or have contraindications to it, we choose an alternative glucose-lowering medication guided initially by patient comorbidities, and in particular, the presence of atherosclerotic CVD ASCVD or albuminuric chronic kidney disease.

See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'. When compared with placebo, the GLP-1 receptor agonists liraglutide , semaglutide , and dulaglutide demonstrated favorable atherosclerotic cardiovascular and kidney outcomes [ ].

The SGLT2 inhibitors empagliflozin , canagliflozin , and dapagliflozin have also demonstrated benefit, especially for HF hospitalization, risk of kidney disease progression, and mortality [ ]. Patients at high CVD risk but without a prior event might benefit, but the data are less supportive.

Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria. To select a medication, we use shared decision-making with a focus on beneficial and adverse effects within the context of the degree of hyperglycemia as well as a patient's comorbidities and preferences.

As examples:. SGLT2 inhibitors with cardiovascular benefit empagliflozin or canagliflozin are good alternatives, especially in the presence of HF. Given the high cost of these classes of medications, formulary coverage often determines the choice of the first medication within the class.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.

Choice of agent is primarily dictated by provider preference, insurance formulary restrictions, eGFR, and cost. In the setting of declining eGFR, the main reason to prescribe SGLT2 inhibitors is to reduce progression of DKD.

However, kidney and cardiac benefits have been shown in patients with eGFR below this threshold. Dosing in the setting of DKD is reviewed in detail elsewhere. See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.

An alternative or an additional agent may be necessary to achieve glycemic goals. GLP-1 receptor agonists are an alternative in patients with DKD as their glycemic effect is not related to eGFR. In addition, GLP-1 receptor agonists have been shown to slow the rate of decline in eGFR and prevent worsening of albuminuria.

See 'Microvascular outcomes' below and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

Of note, we avoid use of SGLT2 inhibitors in patients with frequent bacterial urinary tract infections or genitourinary yeast infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol abuse disorder because of increased risk while using these agents.

SLGT2 inhibitors should be held for 3 to 4 days before procedures including colonoscopy preparation and with poor oral intake to prevent diabetic ketoacidosis. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'.

Repaglinide acts at the sulfonylurea receptor to increase insulin secretion but is much shorter acting than sulfonylureas and is principally metabolized by the liver, with less than 10 percent renally excreted.

Limited data suggest that dipeptidyl peptidase 4 DPP-4 inhibitors are effective and relatively safe in patients with chronic kidney disease.

However, linagliptin is the only DPP-4 inhibitor that does not require a dose adjustment in the setting of kidney failure. GLP-1 receptor agonists may also be used safely in chronic kidney disease stage 4, but patient education for signs and symptoms of dehydration due to nausea or satiety is warranted to reduce the risk of acute kidney injury.

Insulin may also be used, with a greater portion of the total daily dose administered during the day due to the risk of hypoglycemia, especially overnight, in chronic kidney disease and end-stage kidney disease ESKD. See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Patients not on dialysis'.

Without established cardiovascular or kidney disease — For patients without established CVD or kidney disease who cannot take metformin , many other options for initial therapy are available table 1.

We suggest choosing an alternative glucose-lowering medication guided by efficacy, patient comorbidities, preferences, and cost. Although historically insulin has been used for type 2 diabetes only when inadequate glycemic management persists despite oral agents and lifestyle intervention, there are increasing data to support using insulin earlier and more aggressively in type 2 diabetes.

By inducing near normoglycemia with intensive insulin therapy, both endogenous insulin secretion and insulin sensitivity improve; this results in better glycemic management, which can then be maintained with diet, exercise, and oral hypoglycemics for many months thereafter.

Insulin may cause weight gain and hypoglycemia. See "Insulin therapy in type 2 diabetes mellitus", section on 'Indications for insulin'. If type 1 diabetes has been excluded, a GLP-1 receptor agonist is a reasonable alternative to insulin [ 66,67 ].

The frequency of injections and proved beneficial effects in the setting of CVD are the major differences among the many available GLP-1 receptor agonists. In practice, given the high cost of this class of medications, formulary coverage often determines the choice of the first medication within the class.

Cost and insurance coverage may limit accessibility and adherence. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Patient selection'. Each one of these choices has individual advantages, benefits, and risks table 1.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Patient selection' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Potential indications'.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Weight loss' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Weight loss'.

The choice of sulfonylurea balances glucose-lowering efficacy, universal availability, and low cost with risk of hypoglycemia and weight gain.

Pioglitazone , which is generic and another relatively low-cost oral agent, may also be considered in patients with specific contraindications to metformin and sulfonylureas. However, the risk of weight gain, HF, fractures, and the potential increased risk of bladder cancer raise the concern that the overall risks and cost of pioglitazone may approach or exceed its benefits.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Potential indications'. For patients who are starting sulfonylureas, we suggest initiating lifestyle intervention first, at the time of diagnosis, since the weight gain that often accompanies a sulfonylurea will presumably be less if lifestyle efforts are underway.

However, if lifestyle intervention has not produced a significant reduction in symptoms of hyperglycemia or in glucose values after one or two weeks, then the sulfonylurea should be added. Side effects may be minimized with diabetes self-management education focusing on medication reduction or omission with changes in diet, food accessibility, or activity that may increase the risk of hypoglycemia.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Suggested approach to the use of GLP-1 receptor agonist-based therapies' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Mechanism of action' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Mechanism of action' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia'.

Symptomatic catabolic or severe hyperglycemia — The frequency of symptomatic or severe diabetes has been decreasing in parallel with improved efforts to diagnose diabetes earlier through screening. If patients have been drinking a substantial quantity of sugar-sweetened beverages, reduction of carbohydrate intake, and rehydration with sugar-free fluids will help to reduce glucose levels within several days.

See "Insulin therapy in type 2 diabetes mellitus", section on 'Initial treatment'. However, for patients who are injection averse, initial therapy with high-dose sulfonylurea is an alternative option.

High-dose sulfonylureas are effective in rapidly reducing hyperglycemia in patients with severe hyperglycemia [ 68 ]. Metformin monotherapy is not helpful in improving symptoms in this setting, because the initial dose is low and increased over several weeks. However, metformin can be started at the same time as the sulfonylurea, slowly titrating the dose upward.

Once the diet has been adequately modified and the metformin dose increased, the dose of sulfonylurea can be reduced and potentially discontinued. Patients with type 2 diabetes require relatively high doses of insulin compared with those needed for type 1 diabetes.

Insulin preparations, insulin regimens, and timing of dosing are discussed in detail elsewhere. See "Insulin therapy in type 2 diabetes mellitus". See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Administration'. We typically use glimepiride 4 or 8 mg once daily.

An alternative option is immediate-release glipizide 10 mg twice daily or, where available, gliclazide immediate-release 80 mg daily. We contact the patient every few days after initiating therapy to make dose adjustments increase dose if hyperglycemia does not improve or decrease dose if hyperglycemia resolves quickly or hypoglycemia develops.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Sulfonylureas'. Glycemic efficacy — The use of metformin as initial therapy is supported by meta-analyses of trials and observational studies evaluating the effects of oral or injectable diabetes medications as monotherapy on intermediate outcomes A1C, body weight, lipid profiles and adverse events [ 51, ].

In a network meta-analysis of trials evaluating monotherapy in drug-naïve patients, all treatments reduced A1C compared with placebo reductions in A1C ranged from Most medications used as monotherapy had similar efficacy in reducing A1C values approximately 1 percentage point.

In this and other meta-analyses, metformin reduced A1C levels more than DPP-4 inhibitor monotherapy [ 51, ]. There are few high-quality, head-to-head comparison trials of the available oral agents. In one such trial, A Diabetes Outcome Progression Trial ADOPT , recently diagnosed patients with type 2 diabetes were randomly assigned to monotherapy with the thiazolidinedione rosiglitazone , metformin , or glyburide [ 72 ].

At the four-year evaluation, 40 percent of the subjects in the rosiglitazone group had an A1C value less than 7 percent, as compared with 36 percent in the metformin group and 26 percent in the glyburide group.

Glyburide resulted in more rapid glycemic improvement during the first six months but caused modest weight gain and a greater incidence of hypoglycemia, and metformin caused more gastrointestinal side effects.

Rosiglitazone caused greater increases in weight, peripheral edema, and concentrations of low-density lipoprotein LDL cholesterol.

There was also an unexpected increase in fractures in women taking rosiglitazone. The study was limited by a high rate of withdrawal of study participants. Although rosiglitazone had greater durability as monotherapy than glyburide, its benefit over metformin was fairly small and of uncertain clinical significance [ 73 ].

See "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety'. Cardiovascular outcomes — Cardiovascular benefit has been demonstrated for selected classes of diabetes medications, usually when added to metformin.

See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Monotherapy failure'. The cardiovascular effects of diabetes drugs are reviewed in the individual topics. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus".

In trials of patients with type 2 diabetes with and without chronic kidney disease, GLP-1 receptor agonists slowed the rate of decline in eGFR and prevented worsening of albuminuria [ 54,56,58 ].

These trials and other trials evaluating microvascular outcomes are reviewed in the individual topics. Guidelines — Our approach is largely consistent with American and European guidelines [ 52,74,75 ]. A consensus statement regarding the management of hyperglycemia in type 2 diabetes by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD was developed in and has been updated regularly, with the most recent revision published in [ 75 ].

The guidelines emphasize the importance of individualizing the choice of medications for the treatment of diabetes, considering important comorbidities CVD, HF, or chronic kidney disease; hypoglycemia risk; and need for weight loss and patient-specific factors including patient preferences, values, and cost [ 75 ].

We also agree with the World Health Organization WHO that sulfonylureas have a long-term safety profile, are inexpensive, and are highly effective, especially when used as described above, with patient education and dose adjustment to minimize side effects [ 76 ].

Blood glucose monitoring BGM is not necessary for most patients with type 2 diabetes who are on a stable regimen of diet or oral agents and who are not experiencing hypoglycemia.

BGM may be useful for some patients with type 2 diabetes who use the results to modify eating patterns, exercise, or insulin doses on a regular basis.

See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Type 2 diabetes'.

The balance among efficacy in lowering A1C, side effects, and costs must be carefully weighed in considering which drugs or combinations to choose. Avoiding insulin, the most potent of all hypoglycemic medications, at the expense of poorer glucose management and greater side effects and cost, is not likely to benefit the patient in the long term.

See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Our approach'. SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately.

See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Diabetic kidney disease". These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients.

You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest. Weight reduction through diet, exercise, and behavioral modification can all be used to improve glycemic management, although the majority of patients with type 2 diabetes will require medication.

See 'Diabetes education' above. Glycemic targets are generally set somewhat higher for older adults and for those with comorbidities or a limited life expectancy and little likelihood of benefit from intensive therapy.

See 'Glycemic management' above and "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Choosing a glycemic target'. In the absence of specific contraindications, we suggest metformin as initial therapy for most patients Grade 2B. Although some guidelines and experts endorse the initial use of alternative agents as monotherapy or in combination with metformin, we prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed.

See 'Metformin' above and 'Glycemic efficacy' above. We suggest initiating metformin at the time of diabetes diagnosis Grade 2C , along with consultation for lifestyle intervention. See 'When to start' above. The dose of metformin should be titrated to its maximally effective dose usually mg per day in divided doses over one to two months, as tolerated.

See 'Contraindications to or intolerance of metformin' above. See 'Established cardiovascular or kidney disease' above. The majority of patients in the cardiovascular and renal outcomes trials had established cardiovascular disease CVD or diabetic kidney disease DKD with severely increased albuminuria, and therefore, these are the primary indications for one of these drugs.

See 'Without established cardiovascular or kidney disease' above. Each one of these choices has individual advantages and risks table 1. Choice of medication is guided by efficacy, patient comorbidities, preferences, and cost.

Sulfonylureas remain a highly effective treatment for hyperglycemia, particularly when cost is a barrier. Side effects of hypoglycemia and weight gain can be mitigated with careful dosing and diabetes self-management education.

For patients who are injection averse, initial therapy with high-dose sulfonylurea is an alternative, particularly for patients who have been consuming large amounts of sugar-sweetened beverages, in whom elimination of carbohydrates can be anticipated to cause a reduction in glucose within several days.

See 'Symptomatic catabolic or severe hyperglycemia' above and "Insulin therapy in type 2 diabetes mellitus". Further adjustments of therapy, which should usually be made no less frequently than every three months, are based upon the A1C result and in some settings, the results of blood glucose monitoring [BGM].

See 'Monitoring' above. See "Management of persistent hyperglycemia in type 2 diabetes mellitus" and "Insulin therapy in type 2 diabetes mellitus". Why UpToDate?

Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you. Select the option that best describes you. View Topic. Font Size Small Normal Large. Initial management of hyperglycemia in adults with type 2 diabetes mellitus. Formulary drug information for this topic.

No drug references linked in this topic. Find in topic Formulary Print Share. View in. Language Chinese English. Author: Deborah J Wexler, MD, MSc Section Editor: David M Nathan, MD Deputy Editor: Katya Rubinow, MD Contributor Disclosures. All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan This topic last updated: Dec 23, TREATMENT GOALS Glycemic management — Target glycated hemoglobin A1C levels in patients with type 2 diabetes should be tailored to the individual, balancing the anticipated reduction in microvascular complications over time with the immediate risks of hypoglycemia and other adverse effects of therapy.

Summary of glucose-lowering interventions. UK Prospective Diabetes Study UKPDS Group. Lancet ; Holman RR, Paul SK, Bethel MA, et al. N Engl J Med ; Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. ADVANCE Collaborative Group, Patel A, MacMahon S, et al.

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al.

Symptoms of hypoglycemia include, but are not limited to, shakiness, irritability, confusion, tachycardia, and hunger. Hypoglycemia may be inconvenient or frightening to patients with diabetes. Level 3 hypoglycemia may be recognized or unrecognized and can progress to loss of consciousness, seizure, coma, or death.

Hypoglycemia is reversed by administration of rapid-acting glucose or glucagon. Hypoglycemia can cause acute harm to the person with diabetes or others, especially if it causes falls, motor vehicle accidents, or other injury.

A large cohort study suggested that among older adults with type 2 diabetes, a history of level 3 hypoglycemia was associated with greater risk of dementia Conversely, in a substudy of the ACCORD trial, cognitive impairment at baseline or decline in cognitive function during the trial was significantly associated with subsequent episodes of level 3 hypoglycemia Studies of rates of level 3 hypoglycemia that rely on claims data for hospitalization, emergency department visits, and ambulance use substantially underestimate rates of level 3 hypoglycemia 89 yet reveal a high burden of hypoglycemia in adults over 60 years of age in the community African Americans are at substantially increased risk of level 3 hypoglycemia 90 , In addition to age and race, other important risk factors found in a community-based epidemiologic cohort of older Black and White adults with type 2 diabetes include insulin use, poor or moderate versus good glycemic control, albuminuria, and poor cognitive function Level 3 hypoglycemia was associated with mortality in participants in both the standard and the intensive glycemia arms of the ACCORD trial, but the relationships between hypoglycemia, achieved A1C, and treatment intensity were not straightforward.

An association of level 3 hypoglycemia with mortality was also found in the ADVANCE trial An association between self-reported level 3 hypoglycemia and 5-year mortality has also been reported in clinical practice Glucose variability is also associated with an increased risk for hypoglycemia Young children with type 1 diabetes and the elderly, including those with type 1 and type 2 diabetes 86 , 95 , are noted as particularly vulnerable to hypoglycemia because of their reduced ability to recognize hypoglycemic symptoms and effectively communicate their needs.

Individualized glucose targets, patient education, dietary intervention e. CGM with automated low glucose suspend and hybrid closed-loop systems have been shown to be effective in reducing hypoglycemia in type 1 diabetes For patients with type 1 diabetes with level 3 hypoglycemia and hypoglycemia unawareness that persists despite medical treatment, human islet transplantation may be an option, but the approach remains experimental 98 , This change reflects the results of the ADAG study, which demonstrated that higher glycemic targets corresponded to A1C goals An additional goal of raising the lower range of the glycemic target was to limit overtreatment and provide a safety margin in patients titrating glucose-lowering drugs such as insulin to glycemic targets.

This should be reviewed at each patient visit. Hypoglycemia treatment requires ingestion of glucose- or carbohydrate-containing foods — The acute glycemic response correlates better with the glucose content of food than with the carbohydrate content of food.

Pure glucose is the preferred treatment, but any form of carbohydrate that contains glucose will raise blood glucose. Added fat may retard and then prolong the acute glycemic response. In type 2 diabetes, ingested protein may increase insulin response without increasing plasma glucose concentrations Therefore, carbohydrate sources high in protein should not be used to treat or prevent hypoglycemia.

Ongoing insulin activity or insulin secretagogues may lead to recurrent hypoglycemia unless more food is ingested after recovery. Once the glucose returns to normal, the individual should be counseled to eat a meal or snack to prevent recurrent hypoglycemia.

The use of glucagon is indicated for the treatment of hypoglycemia in people unable or unwilling to consume carbohydrates by mouth. Those in close contact with, or having custodial care of, people with hypoglycemia-prone diabetes family members, roommates, school personnel, childcare providers, correctional institution staff, or coworkers should be instructed on the use of glucagon, including where the glucagon product is kept and when and how to administer it.

An individual does not need to be a health care professional to safely administer glucagon. In addition to traditional glucagon injection powder that requires reconstitution prior to injection, intranasal glucagon and ready-to-inject glucagon preparations for subcutaneous injection are available.

Care should be taken to ensure that glucagon products are not expired. Hypoglycemia prevention is a critical component of diabetes management. BGM and, for some patients, CGM are essential tools to assess therapy and detect incipient hypoglycemia.

Patients should understand situations that increase their risk of hypoglycemia, such as when fasting for laboratory tests or procedures, when meals are delayed, during and after the consumption of alcohol, during and after intense exercise, and during sleep.

Hypoglycemia may increase the risk of harm to self or others, such as when driving. Teaching people with diabetes to balance insulin use and carbohydrate intake and exercise are necessary, but these strategies are not always sufficient for prevention 82 , — Formal training programs to increase awareness of hypoglycemia and to develop strategies to decrease hypoglycemia have been developed, including the Blood Glucose Awareness Training Programme, Dose Adjusted for Normal Eating DAFNE , and DAFNEplus.

Conversely, some individuals with type 1 diabetes and hypoglycemia who have a fear of hyperglycemia are resistant to relaxation of glycemic targets 78 , Regardless of the factors contributing to hypoglycemia and hypoglycemia unawareness, this represents an urgent medical issue requiring intervention.

In type 1 diabetes and severely insulin-deficient type 2 diabetes, hypoglycemia unawareness or hypoglycemia-associated autonomic failure can severely compromise stringent diabetes control and quality of life.

This syndrome is characterized by deficient counterregulatory hormone release, especially in older adults, and a diminished autonomic response, which are both risk factors for and caused by hypoglycemia. Hence, patients with one or more episodes of clinically significant hypoglycemia may benefit from at least short-term relaxation of glycemic targets and availability of glucagon Any person with recurrent hypoglycemia or hypoglycemia unawareness should have their glucose management regimen adjusted.

With the advent of CGM and CGM-assisted pump therapy, there has been a promise of alarm-based prevention of hypoglycemia , These studies had differing A1C at entry and differing primary end points and thus must be interpreted carefully.

Real-time CGM studies can be divided into studies with elevated A1C with the primary end point of A1C reduction and studies with A1C near target with the primary end point of reduction in hypoglycemia , — In people with type 1 and type 2 diabetes with A1C above target, CGM improved A1C between 0.

A recent report in people with type 1 diabetes over the age of 60 years revealed a small but statistically significant decrease in hypoglycemia No study to date has reported a decrease in level 3 hypoglycemia.

In a single study using intermittently scanned CGM, adults with type 1 diabetes with A1C near goal and impaired awareness of hypoglycemia demonstrated no change in A1C and decreased level 2 hypoglycemia For people with type 2 diabetes, studies examining the impact of CGM on hypoglycemic events are limited; a recent meta-analysis does not reflect a significant impact on hypoglycemic events in type 2 diabetes , whereas improvements in A1C were observed in most studies — Overall, real-time CGM appears to be a useful tool for decreasing time spent in a hypoglycemic range in people with impaired awareness.

For type 2 diabetes, other strategies to assist patients with insulin dosing can improve A1C with minimal hypoglycemia , Stressful events e.

may worsen glycemic control and precipitate diabetic ketoacidosis or nonketotic hyperglycemic hyperosmolar state, life-threatening conditions that require immediate medical care to prevent complications and death.

Any condition leading to deterioration in glycemic control necessitates more frequent monitoring of blood glucose; ketosis-prone patients also require urine or blood ketone monitoring.

If accompanied by ketosis, vomiting, or alteration in the level of consciousness, marked hyperglycemia requires temporary adjustment of the treatment regimen and immediate interaction with the diabetes care team.

The patient treated with noninsulin therapies or medical nutrition therapy alone may require insulin. Adequate fluid and caloric intake must be ensured. Infection or dehydration are more likely to necessitate hospitalization of individuals with diabetes versus those without diabetes.

A physician with expertise in diabetes management should treat the hospitalized patient. Suggested citation: American Diabetes Association Professional Practice Committee. Glycemic targets: Standards of Medical Care in Diabetes— Diabetes Care ;45 Suppl.

Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation.

Previous Article Next Article. Assessment of Glycemic Control. Glycemic Goals. Intercurrent Illness. Article Navigation. Standards of Care December 16 Glycemic Targets: Standards of Medical Care in Diabetes— American Diabetes Association Professional Practice Committee American Diabetes Association Professional Practice Committee.

This Site. Google Scholar. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. View Large. Number of days CGM device is worn recommend 14 days 2.

Mean glucose 4. Glucose management indicator 5. Figure 6. View large Download slide. Effect of flash glucose monitoring on glycemic control, hypoglycemia, diabetes-related distress, and resource utilization in the Association of British Clinical Diabetologists ABCD nationwide audit.

Search ADS. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes UKPDS 35 : prospective observational study.

Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care. Time in range-A1c hemoglobin relationship in continuous glucose monitoring of type 1 diabetes: a real-world study. Estimation of hemoglobin A1c from continuous glucose monitoring data in individuals with type 1 diabetes: is time in range all we need?

Improved time in range over 1 year is associated with reduced albuminuria in individuals with sensor-augmented insulin pump-treated type 1 diabetes. The relationships between time in range, hyperglycemia metrics, and HbA1c.

Glycemic outcomes in adults with T1D are impacted more by continuous glucose monitoring than by insulin delivery method: 3 years of follow-up from the COMISAIR study. Frequent monitoring of A1C during pregnancy as a treatment tool to guide therapy. The fallacy of average: how using HbA 1c alone to assess glycemic control can be misleading.

Empirically establishing blood glucose targets to achieve HbA 1c goals. Are there clinical implications of racial differences in HbA 1c? A difference, to be a difference, must make a difference.

Racial differences in the relationship of glucose concentrations and hemoglobin A1c levels. HbA 1c performance in African descent populations in the United States with normal glucose tolerance, prediabetes, or diabetes: a scoping review.

Association of sickle cell trait with hemoglobin A1c in African Americans. Impact of common genetic determinants of hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis.

Relationship of A1C to glucose concentrations in children with type 1 diabetes: assessments by high-frequency glucose determinations by sensors. Diabetes screening with hemoglobin A 1c versus fasting plasma glucose in a multiethnic middle-school cohort.

Racial disparity in A1C independent of mean blood glucose in children with type 1 diabetes. Differences for percentage times in glycemic range between continuous glucose monitoring and capillary blood glucose monitoring in adults with type 1 diabetes: analysis of the REPLACE-BG dataset.

The relationship of hemoglobin A1C to time-in-range in patients with diabetes. Clinical recommendations for the use of the ambulatory glucose profile in diabetes care. How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with type 1 diabetes?

Real world hybrid closed-loop discontinuation: predictors and perceptions of youth discontinuing the G system in the first 6 months. Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease. Association between continuous glucose monitoring-derived time in range, other core metrics, and albuminuria in type 2 diabetes.

Time in range is associated with carotid intima-media thickness in type 2 diabetes. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD.

Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Clinical effectiveness of telemedicine in diabetes mellitus: a meta-analysis of 42 randomized controlled trials.

COVID pandemic lockdown in young people with type 1 diabetes: positive results of an unprecedented challenge for patients through telemedicine and change in use of continuous glucose monitoring.

Impact of COVID lockdown on flash and real-time glucose sensor users with type 1 diabetes in England. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy.

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes UKPDS Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS HbA 1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study.

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes UKPDS 36 : prospective observational study. Glucose control and vascular complications in veterans with type 2 diabetes. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Cardiovascular risk reduction with liraglutide: an exploratory mediation analysis of the LEADER trial.

Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. Metabolic profiles and treatment gaps in young-onset type 2 diabetes in Asia the JADE programme : a cross-sectional study of a prospective cohort.

Age at diagnosis of type 2 diabetes mellitus and associations with cardiovascular and mortality risks. Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: a nationwide observational study.

Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in type 2 diabetes.

Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials. A position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association.

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.

The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial. Potential overtreatment of diabetes mellitus in older adults with tight glycemic control.

The association of severe hypoglycemia with incident cardiovascular events and mortality in adults with type 2 diabetes. Management of hyperglycemia in type 2 diabetes, Management of hyperglycemia in type 2 diabetes, a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.

Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial DCCT on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications EDIC Study.

Standardizing clinically meaningful outcome measures beyond HbA 1c for type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M.

and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil.

Early hypoglycaemia and adherence after basal insulin initiation in a nationally representative sample of Medicare beneficiaries with type 2 diabetes. Comparison of CGM-derived measures of glycemic variability between pancreatogenic diabetes and type 2 diabetes mellitus.

Impact of severe hypoglycaemia on psychological outcomes in adults with Type 2 diabetes: a systematic review. Determining the optimal fasting glucose target for patients with type 2 diabetes: Results of the multicentre, open-label, randomized-controlled FPG GOAL trial.

Impact of the FreeStyle Libre flash glucose monitoring system on diabetes self-management practices and glycemic control among patients with type 2 diabetes in Saudi Arabia: A prospective study.

Self-management group education to reduce fear of hypoglycemia as a barrier to physical activity in adults living with type 1 diabetes: a pilot randomized controlled trial. Efficacy and safety of glucose-lowering agents in patients with type 2 diabetes: a network meta-analysis of randomized, active comparator-controlled trials.

Hypoglycaemia Awareness Restoration Programme for People with Type 1 Diabetes and Problematic Hypoglycaemia Persisting Despite Optimised Self-care HARPdoc : protocol for a group randomised controlled trial of a novel intervention addressing cognitions.

The attitude of healthcare professionals plays an important role in the uptake of diabetes self-management education: analysis of the Barriers to Uptake of Type 1 Diabetes Education BUD1E study survey.

Hypoglycaemia in type 1 diabetes: technological treatments, their limitations and the place of psychology. Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U. DAFNE experience. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus.

Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Surveillance of hypoglycemia-limitations of emergency department and hospital utilization data. Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities ARIC Study.

High rates of severe hypoglycemia among African American patients with diabetes: the surveillance, prevention, and Management of Diabetes Mellitus SUPREME-DM network. Increased mortality of patients with diabetes reporting severe hypoglycemia. Machine learning based study of longitudinal HbA1c trends and their association with all-cause mortality: analyses from a National Diabetes Registry.

Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society.

High ketones can be an early sign of diabetic ketoacidosis, which is a medical emergency and needs to be treated immediately. Ketones are a kind of fuel produced when fat is broken down for energy. When too many ketones are produced too fast, they can build up in your body and cause diabetic ketoacidosis, or DKA.

DKA is very serious and can cause a coma or even death. Common symptoms of DKA include:. If you think you may have DKA, test your urine for ketones.

Follow the test kit directions, checking the color of the test strip against the color chart in the kit to see your ketone level. If your ketones are high, call your health care provider right away.

DKA requires treatment in a hospital. Talk to your doctor about how to keep your blood sugar levels within your target range.

Your doctor may suggest the following:. Carbs in food make your blood sugar levels go higher after you eat them than when you eat proteins or fats. You can still eat carbs if you have diabetes. The amount you can have and stay in your target blood sugar range depends on your age, weight, activity level, and other factors.

Counting carbs in foods and drinks is an important tool for managing blood sugar levels. Make sure to talk to your health care team about the best carb goals for you. The A1C test is a simple blood test that measures your average blood sugar levels over the past 2 or 3 months.

A1C testing is part of the ABCs of diabetes—important steps you can take to prevent or delay health complications down the road:. Work with your doctor to establish a personal A1C goal for you. Eating a healthy diet with plenty of fruit and vegetables, maintaining a healthy weight , and getting regular physical activity can all help.

Other tips include:. Medicare , Medicaid, and most private insurance plans pay for the A1C test and fasting blood sugar test as well as some diabetes supplies. Check your plan or ask your health care team for help finding low-cost or free supplies, and see How to Save Money on Diabetes Care for more resources.

Skip directly to site content Skip directly to search. Español Other Languages. Manage Blood Sugar. Español Spanish Print. Minus Related Pages. Hypoglycemia Unawareness. Learn More. Monitoring Your Blood Sugar All About Your A1C 10 Surprising Things That Can Spike Your Blood Sugar Living With Diabetes Diabetes Self-Management Education and Support.

Last Reviewed: September 30, Source: Centers for Disease Control and Prevention. Facebook Twitter LinkedIn Syndicate. home Diabetes Home.

During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. Conclusions and Relevance Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA 1c.

Further research is needed to assess clinical outcomes and longer-term adverse effects. Trial Registration clinicaltrials. gov Identifier: NCT Intensive insulin therapy resulting in good glycemic control has been shown to prevent and reduce the progression of diabetes-related complications in patients with type 1 diabetes.

In recent years, continuous glucose monitoring CGM has become an option for optimal insulin dosing and other activities. CGM systems include a subcutaneous sensor with a transmitter attached and continuous reporting of glucose levels and trends to the patient by a handheld monitor. Data from clinical trials of CGM have been mixed regarding its effect on glycemic control.

The aim of this study was to analyze the effect of CGM on glycemic control, hypoglycemia, well-being, and glycemic variability in individuals with type 1 diabetes treated with multiple daily insulin injections. The GOLD trial was approved by the ethics committee at the University of Gothenburg, Gothenburg, Sweden.

All participants provided verbal and written informed consent trial protocol in Supplement 1. The study was an investigator-initiated randomized, open-label, clinical trial with a crossover design conducted at 15 sites in Sweden. The study took place from February 24, , to June 1, After a run-in period of up to 6 weeks, patients were randomized to receive CGM or conventional treatment for 26 weeks with a week washout between treatment periods Figure 1.

Individuals aged 18 years or older with hemoglobin A 1c HbA 1c of at least 7. Patients were required to have a fasting C-peptide level of less than 0. Race and ethnicity were classified by the investigator or other research staff; if there was any uncertainty, the final decision was made in collaboration with the participant.

Patients treated with insulin pumps were excluded. The study design, including other inclusion and exclusion criteria, have been described elsewhere. Gothia Forum Gothenburg, Sweden performed trial monitoring. During a 6-week run in, patients completed masked CGM for 2 weeks and questionnaires regarding the following characteristics: subjective well-being World Health Organization-5 [WHO-5] , 12 treatment satisfaction Diabetes Treatment Satisfaction Questionnaire [status version and change version] , 13 - 15 fear of hypoglycemia Hypoglycemia Fear Survey , 16 - 18 hypoglycemic confidence Hypoglycemia Confidence Questionnaire , and diabetes-related distress Problem Areas in Diabetes Scale.

Patients were randomized into the first treatment period to CGM using the Dexcom G4 PLATINUM stand-alone system or conventional therapy. CGM was compared with conventional therapy using only self-monitoring of blood glucose.

Patients were not blinded to treatment. All patients received basic instruction on insulin dosing, such as bolus correction, food choices, and the effect of physical activity on glucose control.

Alarm settings were introduced no later than 2 weeks after randomization. At each visit, patients were encouraged to use CGM information at least every 1 to 2 hours during daytime. Insulin dosing was based on self-measurement of blood glucose and not CGM values.

Assessment of HbA 1c was blinded to treatment status. During the week washout period, patients used conventional therapy and masked CGM was performed for 2 weeks. Patients were assessed at the start of each treatment period and at weeks 2, 4, 13, and HbA 1c was measured at all visits in each treatment period except week 2.

Masked CGM was performed 2 weeks before both treatment periods. During conventional therapy, masked CGM was also performed during 2 of the 4 last weeks to evaluate total time in hypoglycemia, euglycemia, hyperglycemia, and glycemic variability.

At all visits, CGM and self-measurements of blood glucose data were downloaded and used to assess glucose levels, number of self-measurements of blood glucose, time CGM was in use, and for optimizing glycemic control.

To maintain an equal number of visits for both treatment periods, the study did not permit extra patient visits for improving glycemic control.

The primary end point was the difference in HbA 1c between CGM and conventional therapy at weeks 26 and Secondary end points included mean amplitude glycemic excursions 22 ; the standard deviation of glucose levels; and the amount of time in hypoglycemia, hyperglycemia, and euglycemia during CGM use.

Other end points were the number of self-measurements of blood glucose and rate of severe hypoglycemia, defined as unconsciousness from hypoglycemia or requiring assistance from another person.

All end points were described in the original protocol submitted to the ethical committee before study start Supplement 1. At study start, the protocol was amended to substitute number of self-measurements of blood glucose as an end point for total insulin dose, and the Hypoglycemia Confidence Questionnaire was added.

The reduction 0. No interim analysis was performed. The full analysis set consisted of all randomized patients who had at least 1 follow-up measurement in each treatment period. The safety analysis consisted of all randomized patients who received treatment CGM or conventional therapy at any time with patients assigned to treatment administered but not randomized treatment.

The primary efficacy analysis was the difference in HbA 1c at weeks 26 and 69 between CGM and conventional therapy for the full analysis set, with adjustment for treatment period and patient effects using procedure for generalized linear models in SAS software, with sequence, patient sequence , period, and treatment as class variables.

The last observation carried forward principle was applied for any missing efficacy measurements from the last weeks of each treatment period. Last observation carried forward was not applied to measurements at the first visit in each treatment period.

A post hoc sensitivity analysis of primary outcome was performed by multiple imputation with 50 study samplings on all patients randomized by using demographics, baseline characteristics, baseline comorbidities, and HbA 1c values at run in and randomization as imputation variables.

A second post hoc sensitivity analysis investigating the effect of the site and interaction between site and treatment modeled as fixed effects on the primary outcome was performed.

Secondary efficacy analyses of normally distributed variables were also adjusted for treatment period and patient effects on the full analysis set. For other secondary efficacy variables, the Fisher nonparametric 2-sample permutation test was used to test between treatment sequences on period changes except for analysis of the occurrence of severe hypoglycemic events in which the treatment groups were handled as 2 independent samples and tested using the Fisher exact test.

The theory of sequential multiple test procedures was applied for the primary and secondary confirmatory analyses. If a 2-sided test gave a significant result at the. All these significant tests were then considered confirmatory. All other end points are considered descriptive and are presented in eTable 3 in Supplement 2.

The numbers of patients screened, randomized, and not completing the study are shown in Figure 1. There were patients randomized between February and December The mean age was Of the randomized patients, Characteristics of patients in the full analysis set population by treatment sequence are shown in Table 1.

The mean SD age was Mean HbA 1c was 8. Data from the run-in visit are provided in Table 2. For the primary efficacy outcome HbA 1c , full analysis set population, the LOCF imputation was done for 2 2.

Results of prespecified analyses of the primary and secondary end points are shown in Table 3. For the primary efficacy analysis, mean SD HbA 1c during CGM use was 7.

HbA 1c was lower in CGM-treated patients during the first and second treatment periods, whereas levels were similar at the beginning of both periods Figure 2.

The standard deviation of blood glucose estimated by CGM and compared with masked CGM during conventional treatment was lower during CGM use than conventional therapy Results of prespecified analyses of patient-reported outcomes of well-being and diabetes treatment satisfaction are shown in Table 3.

Overall well-being, estimated with the WHO-5 questionnaire, improved during CGM use Treatment satisfaction was higher during CGM use as measured by the Diabetes Treatment Satisfaction Questionnaire status version The Hypoglycemia Confidence Questionnaire scale showed less hypoglycemia fear in favor of CGM 3.

Using the theory of sequential tests, the analysis of the primary variable HbA 1c and the secondary variables mean glucose levels, mean amplitude of glycemic excursions, standard deviation of glucose levels, Diabetes Treatment Satisfaction Questionnaire status and change versions, and WHO-5 Well-Being Index were considered confirmatory.

Other secondary end points were not tested, and descriptive data for these variables are shown in eTable 3 in Supplement 2.

Overall mean time of CGM use, estimated by the proportion of CGM data downloaded in relation to follow-up time, was CGM use ranged between HbA 1c was reduced by 0. Patients performed a mean SD of 2. There were 19 patients Patient characteristics are shown in eTable 2 in Supplement 2.

These patients were younger In the first treatment period, 16 of these 19 patients had follow-up data of the primary effect variable HbA 1c. There were 5 events of severe hypoglycemia during conventional treatment event rate, 0.

There were 7 severe hypoglycemia events during the washout period when patients were undergoing conventional therapy event rate, 0. In total, there were 77 patients with adverse events during CGM and 67 patients with adverse events during conventional therapy eTable 4 in Supplement 2.

There were no obvious numerical differences for any adverse event between the treatments. One patient in the CGM group discontinued use because of an allergic reaction to the sensor. There were 7 patients with a total of 9 serious adverse events during CGM treatment and 3 patients with total of 9 serious adverse events during conventional treatment eTable 5 in Supplement 2.

Ketoacidosis was not reported during the study. The second sensitivity analysis of primary outcome adjusted for the site effect and interaction between site and treatment showed an HbA 1c reduction of 0.

The weight at the end of conventional therapy was In this crossover study of persons with type 1 diabetes treated with multiple daily insulin injections, CGM was associated with a mean HbA 1c level that was 0. Moreover, glycemic variability was reduced by CGM. Subjective well-being and treatment satisfaction were greater during CGM than conventional therapy.

The population evaluated in the current study differs to a great extent from earlier clinical trials of CGM. In contrast to earlier trials, the current study had no upper limit of HbA 1c for inclusion, which includes the group of patients with the greatest excess mortality 27 , 28 and the highest risk of diabetic complications since an exponential relationship exists between higher HbA 1c levels and diabetic complications.

Baseline HbA 1c was also high 8. Also in contrast to earlier CGM-studies, 7 - 10 , 25 , 26 the current trial had no limit on the number of self-measurement of blood glucose patients were required to perform for inclusion.

Patients who do not perform self-measurement of blood glucose regularly have higher HbA 1c levels. Hence, evaluating alternative glucose monitoring strategies for these patients is also important.

In the present study, patients performed self-measurement of blood glucose less during CGM than conventional therapy 2. When used in connection with an insulin pump, CGM may ease adjusting insulin doses with respect to observed CGM patterns.

In accordance with earlier findings, 9 these results also suggest that the effectiveness of CGM depends on uninterrupted use during multiple daily insulin injections treatment. Our study increases knowledge in the field of type 1 diabetes in reporting that CGM may be a beneficial option for multiple daily insulin injections—treated patients with respect to HbA 1c levels.

A novel feature of this trial is a more comprehensive investigation of psychosocial variables, which are now recognized as a high priority in clinical diabetes guidelines.

The positive effect on well-being is consistent with previous studies that have shown a significant effect due to CGM on the physical component subscale of the SF Short Form Health Survey.

Indeed, less time in hypoglycemia is known to be associated with better quality of life 33 , 34 and a lower risk of severe hypoglycemia. Of note from a safety perspective, there were numerically more severe hypoglycemic episodes 5 vs 1 during conventional compared with CGM therapy.

In addition, 7 severe hypoglycemia events occurred during the washout period of 4 months when patients used conventional therapy. This study had a number of limitations. First, 19 patients approximately Generally, in a parallel-group study, this can lead to an imbalance between groups.

However, in the current study, patients served as their own controls and thus no such problem existed. It has therefore been proposed that the full analysis set population should be used in crossover studies as the main analysis. Sixteen of the 19 patients who had no follow-up data in the second treatment period had HbA 1c data during the first follow-up period.

Among these patients, those with CGM had a 1. There were more patients treated with CGM than conventional therapy who discontinued treatment during the first treatment period.

This was due to patients wanting to continue CGM and therefore not completing the study while receiving conventional therapy in the second period and also due to patients experiencing device-related problems Figure 1.

A second limitation is that the study could not be blinded and hence patients were aware of the intervention. It cannot be excluded that this, to some extent, could have influenced the treatment effect.

Although the current reduction in HbA 1c may be clinically important, other treatment alternatives are needed for persons with type 1 diabetes to obtain good glycemic control on a broad level. In addition, the current results are restricted to patients with HbA 1c of at least 7.

Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of CGM compared with conventional treatment for 26 weeks resulted in lower HbA 1c. Corresponding Author: Marcus Lind, MD, PhD, Diabetes Outpatient Clinic, Uddevalla Hospital, 80 Uddevalla, Sweden lind.

marcus telia. Correction: This article was fixed for an incorrect unit of measure on May 9, Author Contributions: Dr Lind had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: Lind, Dahlqvist, Ólafsdóttir, Ahlén, Nyström, Hellman. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Dr Lind reports receipt of grants from AstraZeneca, Dexcom, and Novo Nordisk; consulting and receipt of honoraria from Novo Nordisk and Rubin Medical; and lecturing for Eli Lilly, AstraZeneca, Novo Nordisk, Medtronic, and Rubin Medical.

Dr Polonsky reports consulting for Dexcom and Abbott Diabetes Care. Dr Hirsch reports consulting for Abbott Diabetes Care, Roche, and Intarcia. He also reports receipt of personal fees from Eli Lilly, Mylan, and Novo Nordisk.

Dr Bolinder reports serving on advisory boards for Abbott Diabetes Care, Insulet, Integrity Applications, Novo Nordisk, and Sanofi; lecturing for Abbott Diabetes Care, AstraZeneca, Novo Nordisk, and Sanofi.

Dr Hellman reports served on advisory boards for Sanofi, Eli Lilly, Merck, Jensen Cilag, Novo Nordisk, AstraZeneca, Dexcom, and Abbott; lecturing for Sanofi, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and AstraZeneca. No other disclosures were reported.

The NU Hospital Group received financial support for the current trial and CGM systems and sensors from Dexcom Inc. Additional Contributions: Steering committee: Lind primary investigator , Polonsky, Hirsch, Heise, Bolinder, and Dahlqvist.

We thank all participating sites for covering costs of the study, including salaries for participating personnel. We thank Nils-Gunnar Pehrsson, BA, Aldina Pivodic, MSc, Cecilia Kjellman, MSc, Mattias Molin, BSc, and Anders Pehrsson, MSc, at the Statistiska konsultgruppen for assistance in statistical calculations.

Statistiska konsultgruppen was paid for its work. We also thank Joseph W. Murphy, JD, for language editing, who was compensated for his work. full text icon Full Text. Download PDF Top of Article Key Points Abstract Introduction Methods Results Discussion Conclusions Article Information References.

Figure 1. Screening, Randomization, and Analysis for Continuous Glucose Monitoring and Conventional Treatment Groups. View Large Download. CGM indicates continuous glucose monitoring. b Patient had no follow-up data reported during period 2 of the study. c Follow-up data maintained during period 2 of the study.

Figure 2. HbA 1c Values at Inclusion, Randomization, and During the 2 Different Periods of Treatment. Table 1. Clinical Characteristics of the Full Analysis Set Population at Baseline and Randomization a. Table 2. Clinical and Questionnaire Data at Run-in Visit a.

Table 3. Primary and Secondary End Points. Supplement 1. Protocol and Amendments GOLD Study. Supplement 2. Randomization eTable 1. Adherence for CGM Treatment Group Safety Population eTable 2.

Difference Between FAS Population and Excluded Patients With Respect to Baseline Data All Patients eTable 3. Descriptive Data for Secondary End Points FAS Population eTable 4. Adverse Events, by System Organ Class and Preferred Term Safety Population eTable 5.

Supplement 3.