Hyperglycemia in elderly -
Hypoglycemia risk factors include previous history of severe hypoglycemia that required hospital or emergency department visits, memory problems, physical frailty, vision problems, and severe medical conditions such as heart, lung, or kidney diseases.
In older individuals with multiple risk factors for hypoglycemia, the goal should not be tight control. Instead, the goal should be the best control that can be achieved without putting the individual at risk for hypoglycemia.
Lastly, it is important to remember that health status is not always stable as we get older, and the need or ability to keep tight glucose control may change over time in older adults.
Goals for all chronic disease, not just blood sugar control, need to be individualized to adapt to the changing circumstances associated with aging. Howard E. LeWine, MD , Chief Medical Editor, Harvard Health Publishing.
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Because older adults with diabetes are quite heterogeneous with respect to their health status and available care support, the goal for hyperglycemia management should be individualized based on their comorbidities and physical and cognitive function status.
Given that type 2 diabetes develops after years of metabolic abnormalities, a thorough medical evaluation in search for existing diabetes complications is warranted even when a new diagnosis is made in an older adult.
The clinical assessment is used to recommend individualized glycemic, blood pressure, and lipid goals for older adults with diabetes. An interdisciplinary expert panel that included geriatricians, endocrinologists, and other diabetes health care providers was convened by the American Diabetes Association at a Consensus Development Conference on Diabetes and Older Adults in Lifestyle interventions, including regular physical activity and mild-moderate weight loss, are the first-line intervention for diabetes prevention and for treatment of hyperglycemia in older people.
Lifestyle interventions are particularly effective in reducing the risk of developing diabetes among older adults 39 , 56 and are also beneficial in improving diabetes management among older adults Lifestyle interventions can reduce insulin resistance and thereby help reverse the vicious cycles in Fig.
However, there is no evidence that lifestyle interventions can reverse the effects of aging on β-cells; thus, such interventions may delay, but are not likely to completely prevent, the ultimate development of hyperglycemia. Regular physical activities for older adults with diabetes, particularly activities of moderate to vigorous intensity, can improve insulin sensitivity Regular physical activities are a useful adjunct to drug therapy to manage glucose levels and may well contribute to enhanced effectiveness of glucose-lowering agents.
Furthermore, increasing physical activity as part of a lifestyle intervention is effective in reducing physical functioning impairment among patients with diabetes, improving glucose, lipid, and blood pressure control, and enhancing weight loss 40 , 56 , 58 — Traditionally, aerobic training activities have been recommended for older adults, given their benefits in cardiorespiratory fitness.
Evidence also supports regular whole-body resistance training for older adults with type 2 diabetes. As previously discussed, the pathophysiology of type 2 diabetes involves insulin resistance, and the main tissues in the body that are sensitive to insulin are muscles and adipose cells.
Resistance training changes body composition e. In fact, physical activity programs that include both aerobic and resistance training improve glycemic levels more than aerobic or resistance training alone 63 , As part of the exercise routine, resistance training should be performed at least twice weekly Given the high prevalence of coronary artery disease in older patients with diabetes, which may be asymptomatic or atypical in symptoms, it is important for such patients to have medically supervised stress testing before entering any challenging exercise training program.
Additional issues to consider in an older person participating in an exercise program include the potential for foot and joint injury with upright exercise, such as jogging, unstable comorbidities, autonomic neuropathy, peripheral neuropathy, or foot lesions that may predispose to injures, and the ability to promptly identify and treat hypoglycemia, which can be induced by exercise if the patient is on insulin or a sulfonylurea.
As part of diabetes management, the American Diabetes Association recommends that overweight adults with type 2 diabetes lose 2—8 kg weight through lifestyle changes Recent studies have not substantiated previous concerns about the risks of weight loss among older adults, where older adults who intentionally lost weight by combining caloric restriction and exercise had minimal reduction in lean muscle mass and actually had increased bone density and improvement in physical function compared with individuals who lost weight by caloric restriction alone or by exercise alone 67 — Hence, weight loss programs for older adults with diabetes should incorporate caloric restriction with physical activity.
Caloric restriction is appropriate for healthier overweight and obese older diabetes patients as part of management of hyperglycemia but is not appropriate for some older patients who are at risk for undernutrition already.
More pressing dietary issues for these patients are how to maintain adequate caloric intake and coordinate food intake with administration of glucose-lowering agents appropriately to avoid hypoglycemia. Older adults with mobility limitation or who lack transportation are likely to have limited access to healthy and fresh food Social isolation i.
The presence of impaired cognitive function may make following a dietary prescription particularly difficult. Furthermore, dietary habits established for a lifetime and often with a cultural background may be particularly difficult to modify.
Problems with taste and oral health, which are common in older people, may further limit adaptation to a prescribed diet Oral health problems can be exacerbated by diabetes, which may increase the rate of periodontal disease.
Xerostomia is also more common in older people owing to decreased salivary gland flow and is sometimes exacerbated by coexisting medication use. Most medications to treat hyperglycemia in older adults with type 2 diabetes target one or more of the pathophysiological impairments of age-related type 2 diabetes: reducing hepatic glucose production, increasing insulin secretion, increasing insulin sensitivity, decreasing glucagon secretion, increasing incretin levels, and decreasing satiety.
Unfortunately, older patients are often underrepresented in large clinical trials; therefore, data on antihyperglycemic medications are often extrapolated from younger populations Treatment of older adults with diabetes needs to account for the progression of type 2 diabetes over time Because of the age-related decline of β-cell function, maintaining target levels of glycemic control may necessitate escalation of drug doses or the addition of other antihyperglycemic agents Thus, medications that target the β-cells, such as sulfonylureas or GLP-1—related drugs, are likely to become less effective over time.
Medications such as metformin, thiazolidinediones TZDs , and sodium glucose transporter 2 SGLT2 inhibitors may help to reverse some of the vicious cycles contributing to hyperglycemia but do not directly address the effects of aging on β-cells.
A review of the pharmacologic treatment for hyperglycemia is beyond the scope of this article but has been extensively discussed elsewhere 75 , Tables 1 and 2 list most of the currently available antihyperglycemic agents noninsulin and insulin , including a brief description of the physiological action of the medication and the advantages and disadvantages of the agent when used by older patients.
Although it is common for an older adult to have multiple comorbidities, impairment in cognition or functional status, and limited financial support, a strong supportive care system may be sufficient to help the patient to safely implement a complex medical treatment plan.
Noninsulin antihyperglycemic agents 75 , Gliclazide a. Rosiglitazone b. Vildagliptin a. Alogliptin c. Lixisenatide a. Bile acid sequestrant d. Bromocriptine, immediate release form c. Pramlintide c. CVD, cardiovascular disease; GI, gastrointestinal; HDL-C, HDL-cholesterol; LDL-C, LDL-cholesterol; MI, myocardial infarction; STOP-NIDDM, Study to Prevent Non-Insulin-Dependent Diabetes Mellitus; T2D, type 2 diabetes.
Insulin for treatment of type 2 diabetes 75 , The insulin agents lead to increased glucose disposal and decreased hepatic glucose production.
Inhaled human insulin Afrezza is contraindicated in patients with chronic lung disease such as asthma or chronic obstructive pulmonary disease.
The treatment plan should minimize risk for hypoglycemia, especially in frail, vulnerable older patients and when using agents with high risk for hypoglycemia such as insulin and sulfonylureas.
Thus, emphasis on lifestyle interventions and classes of drugs that do not cause hypoglycemia can often result in safe achievement of lower A1C targets, especially early in the course of type 2 diabetes. As these safer interventions become less effective as a result of progressive β-cell failure with aging, insulin may be needed, and the A1C target may need to be higher to avoid hypoglycemia.
Sulfonylurea drugs should be used only with extreme caution in any vulnerable older patient. Frequent follow-up should be provided to ensure that the treatment program is progressing smoothly and that hypoglycemia does not occur.
Metformin, a biguanide, is the first-line oral medication for hyperglycemia for older adults Some older patients may experience intolerable gastrointestinal discomfort, decreased appetite, and modest weight loss associated with metformin. Metformin is contraindicated in patients with renal insufficiency, and the U.
Sulfonylureas are probably overused in older adults with type 2 diabetes. These drugs are inexpensive, and their overall safety record is good.
Their primary mechanism of action is to enhance insulin secretion by β-cells of the pancreas. Hypoglycemia is a serious risk, however, and conservative use is thus recommended for older people.
Glyburide is associated with a high risk for hypoglycemia in older patients due to its long half-life so is not recommended in this population Other sulfonylureas may be safer to use in older patients, but all have a hypoglycemia risk.
Another concern about use of sulfonylurea drugs in older adults is a higher secondary failure rate than other drugs, probably related to progressive β-cell dysfunction TZDs improve insulin sensitivity in skeletal muscle, reduce hepatic glucose production, and have the advantages of low risk for hypoglycemia.
However, concerns over potential adverse effects associated with TZDs have been raised, including increased risks of bladder cancer, weight gain, fluid retention, and bone fractures TZDS are usually not considered as first-line antihyperglycemic agents.
GLP-1 is an incretin, an intestinal hormone that is released as glucose levels increase with meals and cause glucose-dependent insulin secretion; therefore, GLP-1 agents are unlikely to cause hypoglycemia.
Two classes of GLP-1 drugs are used clinically:. The injectable GLP-1 receptor agonists stimulate insulin section in a glucose-dependent fashion, suppress glucagon output, slow gastric emptying, and decrease appetite. These agents have the advantages of modest weight loss, but for some patients, the weight loss can be too much and there may be resistance against performing injections.
The oral dipeptidyl peptidase-4 DPP-4 inhibitors enhance circulating concentrations of active GLP When used alone, both classes of GLP-1 agents rarely cause hypoglycemia, but high cost may be prohibitive for some older adults. Pilot studies of myocardial ischemia and animal studies suggested that GLP-1 agonists may improve cardiovascular outcomes, but the results from two recent large trials are mixed.
Among patients with type 2 diabetes and high cardiovascular risk, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke was lower with liraglutide than with placebo 79 , but among patients with type 2 diabetes and recent acute coronary syndrome, no significant effect on the rate of major cardiovascular events was found with lixisenatide compared with placebo SGLT-2 inhibitors allow the kidneys to reabsorb most filtered glucose.
SGLT-2 inhibitors are oral agents that lower glucose levels by increasing urinary excretion of glucose. They are approved for use in both type 1 and type 2 diabetes. They are used once daily, result in modest lowering of A1C similar to DPP-4 inhibitors, and rarely cause hypoglycemia.
They are contraindicated in chronic kidney disease. These agents increase urine volume and sodium excretion, so usually lower blood pressure modestly but may cause volume depletion. This volume effect may contribute to increased risk for diabetic ketoacidosis in people with type 1 diabetes.
There is increased risk for genital yeast infection and urinary tract infection, likely resulting from the induced glycosuria. Because of these adverse effects, relatively high cost, and limited experience with these drugs in older adults, their use is usually reserved for situations in which other classes of drugs are not tolerated.
Because β-cell dysfunction plays a major role in type 2 diabetes in older adults, insulin replacement therapy may be necessary to achieve the goal for hyperglycemia control, especially in patients with longer duration of type 2 diabetes with progressive β-cell dysfunction.
The approach to use of insulin in older adults with type 2 diabetes is to start with a once-daily, long-acting insulin basal insulin , with minimal peak or trough effect. Long-acting agents, such as insulin glargine and detemir insulin, have a lower incidence of nocturnal hypoglycemia than shorter-acting insulin agents, even among older adults Premeal injections of a rapid-acting insulin analog can be added to the basal insulin, if necessary, in older patients in whom the physician has determined can safely administer insulin and monitor for hypoglycemia.
Insulin aspart and insulin lispro have a very rapid onset and short duration of action and are used just before meals. They are less likely to result in postmeal hypoglycemia than human regular insulin These rapid-acting insulin agents can be given within 20 min after starting a meal, and hence, are particularly useful in older patients who may not eat regularly.
Use of combination antihyperglycemic agents in older patients may be necessary with the progression of the disease. Combinations of different classes of drugs are theoretically attractive because their different modes of action address various aspects of the pathophysiology of hyperglycemia.
For older patients who have persistent hyperglycemia above their individualized A1C target with lifestyle intervention and metformin if not contraindicated , adding another agent would be recommended.
The options include adding an oral agent such as short-acting sulfonylurea i. Alternatively, a basal insulin, such as glargine, may be added If a sulfonylurea is already being used, we would recommend tapering it to discontinue because a combination of sulfonylurea and insulin greatly increases the risk of hypoglycemia Older adults are at high risk for the development of type 2 diabetes as a result of the combined effects of genetic, lifestyle, and aging influences.
Despite the advancement in understanding the pathophysiology of type 2 diabetes, more research is needed to elucidate the underlying molecular mechanisms of how aging is related to type 2 diabetes and to diabetes-related complications Prevention of type 2 diabetes and treatment of hyperglycemia in older adults should emphasize lifestyle interventions based on the pathophysiology of the development of type 2 diabetes and their numerous benefits on the overall health of older adults.
With the aging of β-cell function, the addition of one or more medications to achieve glycemic control targets may be needed. However, the overall management of hyperglycemia needs to be individualized for older adults based on individuals' likelihood of benefiting from tight control versus the risks associated with implementing complex management regimens, especially when insulin or a sulfonylurea drug is included.
See accompanying articles, pp. was supported by the VA Career Development Award 1IK2RXA2. The contents do not represent the views of the U. Department of Veterans Affairs or the U. Conflict of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. and J. researched the data, wrote the manuscript, and reviewed and edited the manuscript. 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. Type 2 diabetes in elderly is a powerful risk factor for functional limitations, frailty, loss of independence, and disability Moreover, there is evidence that type 2 diabetes increases the risk of fracture risk and secondary hypogonadism, which also contribute to enhance risk of osteoporosis and muscle weakness in men 27 , With aging there is a progressive loss of strength and toughness of skeletal and muscle mass which leads to a status of osteo- and sarcopenia.
Changes in skeletal muscle protein turnover could accelerate these alterations in type 2 diabetic patients 29 , resulting in a greater risk of falling and bone fractures As testosterone decline with advancing age, the assessment of its concentrations may be useful in case of signs and symptoms of overt hypogonadism to better evaluate the risk of fracture in this selected population 31 , Indeed, there is evidence that older patients with type 2 diabetes have an increased risk of hip fractures, particularly in insulin-treated patients, and non-skeletal fall injuries A moderate but regular physical activity and a high adherence to Mediterranean dietary pattern showed some benefits in reducing the risk of falls and physical impairments in patients older than 75 years 34 , The American Geriatrics Society suggests to interrogate older patients about falls at least every 12 months, examine potentially reversible causes of falls medications, environmental factors, limiting factors and perform a complete basic evaluation when an injurious fall occurs level of evidence III, strength B Urinary incontinence is a frequent comorbidity of diabetes, although it is usually not-reported by patients Therefore, according to the American Geriatrics Society, physicians should always perform an annual screening for urinary incontinence which may be an important cause of social isolation, depression, falls, and fractures level of evidence III, strength A Both overtreatment and polypharmacy are very common among frail older diabetic subjects.
The prevalence of polypharmacy regimen, defined as the use of more than 5 medications, increases with age. Furthermore, one-quarter of US older diabetic adults are on potential overtreatment for tight glycemic control using glucose-lowering medications at high risk of hypoglycemia Polypharmacy in older diabetic patients may produce detrimental effects mainly due to increased risk of drug-drug interactions and adverse side effects However, a deintensification rather than intensification of pharmacological therapy should be advisable in diabetic patients in older age, in consideration of both benefits and risks associated with complex therapeutic regimens.
Moreover, older adults with diabetes should annually update the list of used medications for their own clinicians level of evidence II, strength A Older patients represent a very heterogeneous and challenging population concerning diabetes care and treatment. While treating diabetes in elderly, clinicians should be always aware of maintaining a good quality of life.
Patient-centered glycemic targets are needed in order to achieve the glycemic control avoiding dangerous or extreme glucose excursions. Elderly patients are highly vulnerable to hypoglycemic events, as a consequence of progressive age-related decrease in β-adrenergic receptor function.
Indeed, hypoglycemia in older age has been associated with an increased risk to develop cognitive impairment, dementia, all-cause hospitalization, and all cause mortality 42 — Use of insulin or insulin secretagogues, polypharmacy, coexisting comorbidities, renal insufficiency, dehydration, impairment of counter-regulatory responses represent the main predisposing risk factors for hypoglycemic episodes Assessment of potential risk factors for hypoglycemia is an important part of the clinical management of older diabetic subjects.
Moreover, both patients and caregivers have to be trained and well-educated on the prevention, detection, and treatment of hypoglycemic events On the other hand, both untreated or undertreated hyperglycemic events should be avoided in old people, given the higher risk of dehydration, dizziness, falls, and long-term mortality The paucity of randomized controlled trials RCTs for diabetes treatment in older adults does not allow to clearly establish the most appropriate therapeutic goals in the elderly.
standard therapy, vs. Actually, the best glycemic target to achieve for elderly diabetic patients is still a matter of debate Table 1 summarizes the glycemic goals for elderly affected by diabetes according different international guidelines.
These therapeutic objectives are in line with those for adults older than 65 years indicated by American Geriatrics Society HbA1c ranging between 7.
Beyond tailored glycemic goals, ADA highlights the importance of controlling any other cardiovascular risk factor with an appropriate lipid-lowering, anti-platelet, and anti-hypertensive therapy. Table 1. Glycemic targets in elderly patients according to the current international guidelines.
Differing from ADA, the American Association of Clinical Endocrinologists AACE advises an HbA1c goal of 6.
Studies comparing the effectiveness of anti-diabetes drugs in elderly are lacking, due to the exclusion of older diabetic adults from RCTs, given the high number of comorbidity and their enhanced cardiovascular risk.
Every therapeutic strategy should be chosen considering age, health status, self-manageability, cognitive and nutritional status, and comorbidities Table 2. Generally, in older adults at higher risk to experience hypoglycemic events, medications with low risk of hypoglycemia should be preferred.
Furthermore, it is advisable to simplify poly-pharmacological regimens in order to reduce adverse effects and achieve most appropriate glycemic goals. The latest consensus on the management of hyperglycemia in type 2 diabetes of the ADA and the European Association for the Study of Diabetes EASD 57 recommends to use drugs with proven cardiovascular benefit in patients with established clinical cardiovascular disease.
Anti-hyperglycemic agents considered safe and effective for type 2 diabetic older patients can be divided in oral and injectable drugs Table 3. Table 2. Most frequent clinical phenotypes in elderly with suggested HbA1c target and glucose-lowering treatment. Table 3. Glucose-lowering medications available in Europe with specific characteristics to drive the treatment choice for old people with type 2 diabetes.
Metformin is the first-line medication recommended in the management of type 2 diabetes. It reduces both insulin-resistance and hepatic gluconeogenesis, lowering glucose concentrations without increasing hypoglycemic risk. Moreover, a once daily extended-release formulation of metformin is now available, which is associated with a better gastrointestinal tolerability profile and patients' compliance.
As it is excreted by the urine, a good glomerular filtration rate is needed The main adverse effects described are commonly gastrointestinal symptoms and very rarely lactic acidosis. It is a safe and effective anti-hyperglycemic drug, with low cost, and minimal risk of hypoglycemia. Nevertheless, it should be carefully used under conditions of congestive heart failure and hepatic dysfunction, which could increase the risk of lactic acidosis Thiazolidinediones also act as insulin sensing agent influencing transcriptional processes by activation of peroxisome proliferator-activated receptor-γ PPAR-γ.
Pioglitazone is the only one remaining drug of this class, as it has proven to be safe in the presence of cardiovascular disease It is characterized by good efficacy, low cost, and no risk of hypoglycemia when used in monotherapy. It can be used even in case of low GFR value 61 starting from the lowest dose of 15 mg to the maximum dose of 45 mg with meals.
Pioglitazone is associated with weight gain and fluid retention, so that it is contraindicated in case of congestive heart failure NYHA class III, IV. Furthermore, it is not advisable to use the drug in older person at risk for falls because it has proven to increase risk of non-osteoporotic bone fractures Finally, it is contraindicated in patients with or at high risk for bladder cancer Sulfonylureas are an insulin secretagogue class, which act by favoring β-cells membrane depolarization and consequently insulin secretion.
They are characterized by high glucose lowering efficacy and low cost, but they should be used with extreme caution because of the high risk of hypoglycemia and weigh gain. Short acting ones with lowest hypoglycemic risk, such as gliclazide, should be preferred in older diabetic patients, when initial therapy with metformin is contraindicated or not tolerated By contrast, long acting sulfonylureas, as glibenclamide, are considered inappropriate in elderly diabetes management.
Metiglinides are short-acting insulin secretagogue agents, that enhance early phase of insulin secretion at meals, lowering postprandial glucose levels. They present lower risk of hypoglycemia than sulfonylureas, since their activity is dependent on the presence of glucose Repaglinide is the most effective agent of this class, with a moderate effect on weight gain.
Use of repaglinide may be indicated for elderly patients with type 2 diabetes because of the low risk of hypoglycemia, high efficacy on postprandial hyperglycemia, and safe use in renal impairment Dipeptidyl peptidase 4 DPP-4 inhibitors belong to the class of incretin enhancer agents.
They inhibit the DPP-4 enzyme, thereby extending the life-time of GLP-1 and increasing insulin secretion in a glucose dependent manner. Drugs in this class are generally well-tolerated in older people, with neutral effect on body weight and very low risk of hypoglycemia 66 , DPP-4 inhibitors have proven to be effective in reducing baseline HbA1c levels and fasting plasma glucose Moreover, a study of 80 elderly diabetic patients treated with oral glucose-lowering drug DPP4-inhibitors or sulfonylureas for at least 24 months showed that patients using DPP-4 inhibitors had better sarcopenic parameters fat-free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed as compared with those receiving sulfonylureas The cardiovascular safety of this class of agents has been confirmed by several randomized controlled trials 70 — Alogliptin, saxagliptin, sitagliptin, and linagliptin 70 — 74 have proven to neither increase nor decrease risk of the combined major adverse cardiovascular events MACE in type 2 diabetic patients with established cardiovascular disease.
In the EXAMINE trial, patients with type 2 diabetes and recent acute coronary syndromes assigned to alogliptin had an increased, although non-statistically significant, rate of HF hospitalization when compared to the placebo group Moreover, data from the TECOS trial report that sitagliptin is not associated with a higher fracture risk, major osteoporotic fractures, or hip fractures Therefore, DPP-4 inhibitors may be considered as an effective and safely treatment option for older patients with type 2 diabetes Sodium-glucose cotransporter 2 SGLT-2 inhibitors are the latest marketed oral anti-hyperglycemic agents in diabetes management.
Beyond glucose lowering efficacy, SGLT-2 inhibitors have also beneficial effects in reducing body weight and blood pressure. If SGLT-2 inhibitors are used in combination with diuretics, lowering the dose of diuretics is needed to minimize the risks of hypotension and dehydration SGLT2-inhibitors are generally well-tolerated in older adults, except for increased risk of mycotic genital infections in both sexes.
There is evidence from cardiovascular outcome trials 80 , 81 that this class has beneficial effects in reducing the composite endpoint of cardiovascular deaths, non-fatal myocardial infarction and non-fatal stroke as compared with placebo in patients with type 2 diabetes and high cardiovascular risk.
Similarly, in the multinational, observational CVD-REAL study, new users of empaglifozin, canaglifozin, and dapaglifozin reported lower risk of cardiovascular mortality, MACE and hospitalization for heart failure as compared with new users of other glucose-lowering drugs Moreover, a subgroup analysis of the EMPA-REG OUTCOME study showed a significant reduction in the risk of MACE especially in patients older than 65 years treated with empaglifozin Based on these results, ADA and EASD recommend their use in patients with established or at high risk of cardiovascular disease In the respective RCTs designed to test the efficacy and safety of SGLT-2 inhibitors on renal outcomes 83 , 84 , both empagliflozin and canagliflozin use was associated with reduced risk of sustained loss of kidney function, attenuated GFR decline, and a reduction in albuminuria, which supports a possible renoprotective effect of this drugs in people with type 2 diabetes.
Conversely, on May the Food and Drug Administration released a warning relative to an increased risk of diabetic ketoacidosis DKA associated with use of SGLT-2 inhibitors 86 , on the basis of a comparative evaluation with DPP-4 inhibitors on a cohort of more than , type 2 diabetic patients The increased incidence of DKA related to SGLT2-inhibitors may be probably related to the non-insulin-dependent glucose clearance, hyperglucagonemia, and volume depletion Therefore, although this class has many beneficial effects on cardiovascular and renal outcomes, caution is needed using SGLT2 inhibitors in elderly because of increased risk of genital infections, dehydration, orthostatic hypotension, lower extremities amputations, and bone fracture 89 , Glucagon-like peptide 1 receptor agonists GLP-1RAs are innovative and pleiotropic drugs that act by promoting insulin secretion and reducing glucagon secretion in a glucose dependent manner and favoring weight loss.
As they use the injectable way of administration, they require neuro-psychological and physical integrity. GLP-1RAs are highly effective in lowering glucose levels, with minimal risk of hypoglycemia 91 , The main adverse effects associated with GLP-1RAs use consist of nausea, vomiting, diarrhea, and an increase in heart rate Furthermore, there is strong evidence from RCTs 95 — 97 that these drugs can reduce the risk of MACE in type 2 diabetic patients with high cardiovascular risk.
Results from preclinical studies showed also favorable effects of GLP-1RAs on neuronal protection and cognitive performances 98 , Randomized controlled trials assessing effects of incretin therapy on cognitive function and Alzheimer's disease in humans are currently ongoing.
If these benefits will be confirmed, use of GLP-1RA may be a helpful option even in patients with mild cognitive impairment. Free and fixed-ratio combinations of GLP-1RAs and basal insulin formulations have been approved by regulatory agencies to potentiate antihyperglycemic effects and glycemic control in type 2 diabetic patients 57 , At the moment, two fixed-ratio combinations, insulin glargine plus lixisenatide IGlarLixi and insulin degludec plus liraglutide IDegLira , have been approved for treatment of type 2 diabetes A recent analysis compared effectiveness of fixed-ratio combination iGlarlixi vs.
IGlarLixi was associated with significantly higher HbA1c reductions, weight loss and number of patients reaching HbA1c target despite lower insulin doses, with similar rates oh hypoglycemic events and lower rates of gastrointestinal adverse events.
A meta-analysis of 26 RCTs have shown a mean reduction of 0. Moreover, when compared with intensive insulin therapy, either free or fixed combination of GLP-1RA and basal insulin led to a greater mean decrease of 0.
Based on this evidence, combination strategies, either free or fixed, represent a good option for intensifying basal insulin therapy in patients with type 2 diabetes who need amelioration of glycemic control, without increasing the risk of hypoglycemia and weight gain Insulin remains the most effective drug for type 2 diabetes The main limitations of insulin therapy are the risk of hypoglycemia and weight gain, although it can be administered at any GFR value.
Insulin therapy requires patients' autonomy, intact visual, motor, and cognitive ability in diabetes management Since its discovery in , several and innovative insulin formulations have been developed. Insulin glargine U or U , degludec U or U , and detemir represent long acting insulin analogs which provide daily basal insulin profiles Compared with human insulin neutral protamine Hagedorn NPH , long-acting insulin analogs have a longer duration of action and a fatter pharmacokinetic profile, with a reduced risk of hypoglycemia Therefore, the newer basal insulins should be preferentially used in diabetic elderly, where they may be indicated as starting insulin therapy.
Prandial rapid aspart, lispro, glulisine and ultra-rapid acting faster aspart insulin analogs used at mealtime can be combined with basal insulin to sooner improve and intensify glycemic control However, both basal and prandial insulin require frequent titration to achieve the best anti-hyperglycemic effects.
Patients on enteral or parenteral nutrition may require frequent glucose monitoring intervals of 4—6 h to better titrate the insulin dose and to avoid hypo- and hyperglycemic events Caution is needed in insulin titration because a simple error can easily precipitate major hypoglycemic episodes, leading to falls, and bone fractures Alternatively, premixed insulin regimen, eliminating the challenge of mixing insulin, may have a role in elderly patients who have regular eating habits, with similar efficacy as compared with basal bolus therapy Therefore, use of insulin therapy in elderly patients often requires the assistance of a caregiver if patients' abilities are limited.
Older adults with type 2 diabetes represent a complex and heterogenous age group. Managing diabetes in older age remains an important clinical challenge for all physicians, either primary care providers or specialists. A comprehensive geriatric assessment should be performed at diagnosis of diabetes to better understand cognitive, visual and motor abilities, and coexisting comorbidities.
In the choice of anti-hyperglycemic strategies, drugs with proven tolerability, safety, and minimal hypoglycemic risk should be preferred. Anti-diabetes treatment regimens in elderly must be simple, sustainable, and safe to best mirror patients' preferences, wishes, and needs.
GB, MIM, KE, and DG conceived the manuscript. ML, GB, and MIM drafted the manuscript. JM, KE, and DG reviewed and edited the manuscript. All authors gave the approval to the final version of the manuscript. MIM received a consultancy fee from MSD and has held lectures for Sanofi, Astrazeneca, and Novo Nordisk.
JM has held lectures for Astra Zeneca, Boehringer-Ingelheim, Eli Lilly, MSD, Novo Nordisk, Sanofi, and Servier and received research support from Boehringer-Ingelheim, MSD, Novo Nordisk, Sanofi. KE received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly, Sanofi, and Novo Nordisk.
DG received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Life Expectancy. PubMed Abstract. Health at a Glance: Europe — State of Health in the EU Cycle. Paris: OECD Publishing. doi: CrossRef Full Text. Centers for Disease Control and Prevention.
Life Expectancy by Age, Race, and Sex, — pdf Accessed November 10, GBD causes of death collaborators. global, regional, and national age-sex specific mortality for causes of death, — a systematic analysis for the global burden of disease study Lancet — CrossRef Full Text Google Scholar.
Geneva: World Health Organization World Health Organization. Global Report on Diabetes Kalyani RR, Golden SH, Cefalu WT. Diabetes and aging: unique considerations and goals of care. Diabetes Care — PubMed Abstract CrossRef Full Text Google Scholar. International Diabetes Federation.
IDF Diabetes Atlas. Yang Y, Guo Y, Qian ZM, Ruan Z, Zheng Y, Woodward A, et al. Ambient fine particulate pollution associated with diabetes mellitus among the elderly aged 50 years and older in China.
Environ Pollut. Halter JB, Musi N, McFarland Horne F, Crandall JP, Goldberg A, Harkless L, et al. Diabetes and cardiovascular disease in older adults: current status and future directions.
Diabetes — Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, et al. Consensus development conference on diabetes and older adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. Barzilai N, Cuervo AM, Austad S.
Hypperglycemia Are slderly Warning Signs Hyperglycemia in elderly Eldrrly in Older Adults? Diabetes Hyperglycemia in elderly in older adults can range Enzymes for a healthy gut mild to severe. They include excessive thirst and urination, blurry vision, and fatigue. If you have any of these diabetes warning signs, talk to your doctor. Detecting diabetes early can help prevent serious complications down the road.
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