INTRODUCTION — The prevalence of type 2 diabetes continues to increase steadily as more people live longer and grow heavier. Older adults (>65 years) with diabetes are at risk of developing a similar spectrum of microvascular complications as their younger counterparts, albeit probably at lower absolute risk if they develop diabetes later in life, which will limit duration. On the other hand, their absolute risk for macrovascular complications is substantially higher than for younger people with diabetes. In addition, they are at high risk for polypharmacy, functional disabilities, and other common geriatric syndromes that include cognitive impairment, depression, urinary incontinence, falls, and persistent pain [1].
This topic will review diabetes management in older patients and how management priorities and treatment choices may differ between older and younger patients. The general management of type 2 diabetes is reviewed separately. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus" and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus" and "Management of persistent hyperglycemia in type 2 diabetes mellitus".)
GOALS — Goals for glycemic control, as well as risk factor management, should be based upon the individual's overall health (specifically, serious comorbidities, cognitive functions, and functional status) as it impacts the life expectancy and risk of complications (table 1).
Acute hyperglycemia can increase dehydration and contribute to orthostasis and the risk of falls. In addition, chronic hyperglycemia and its associated effects on neuropathy and cognition add to this risk and may accelerate functional decline with age [2]. On the other hand, older patients may tolerate relatively higher blood glucose levels before they manifest an osmotic diuresis, owing to their lower glomerular filtration rates (GFR) and lower load of glucose delivered to the tubules for reabsorption. Avoidance of hypoglycemia, hypotension, and drug interactions due to polypharmacy are of greater concern in older than in younger patients with diabetes [3]. In addition, management of coexisting medical conditions is important as it influences the ability to perform self-management.
There are few data specifically addressing optimal glycemic goals in medication-treated older patients (>65 years) [4-6]. The following recommendations are based upon trials carried out in the general population and from clinical experience. They are largely consistent with the American Geriatrics Society (AGS), the American Diabetes Association (ADA), the Canadian Diabetes Association, the Endocrine Society, the International Diabetes Federation (IDF), the European Diabetes Working Party, and the American College of Physicians guidelines [1,2,6-13].
Controlling hyperglycemia — Older adults with diabetes are a heterogeneous population that includes persons residing independently in communities, in assisted care facilities, or in nursing homes. They can be fit and healthy, or frail with many comorbidities and functional disabilities. The appropriate target for glycated hemoglobin (A1C) needs to be individualized based on overall health and life expectancy, as well as on identified patient-specific risks for hypoglycemia and on the ability of the patients to adopt and adhere to specific treatment regimens (table 1). The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial suggest that intensive glycemic therapy in persons at high risk for cardiovascular disease (CVD), especially with polypharmacy, may increase the risk for both total and CVD mortality [14-16].
●Healthy older adults – In the absence of any long-term clinical trial data in fit older populations and in those with life expectancy of >10 years, an A1C goal of <7.5 percent (58.5 mmol/mol) should be considered in medication-treated patients. To achieve this goal, fasting and preprandial glucoses should be between 140 and 150 mg/dL (7.8 to 8.3 mmol/L) (calculator 1) [17].
●Older adults with significant comorbidities – The glycemic goal should be somewhat higher (A1C ≤8 percent, fasting and preprandial glucoses between 160 and 170 mg/dL [8.9 to 9.4 mmol/L]) in medication-treated, frail older adults with medical comorbidities and in those whose life expectancy is less than 10 years.
●Older adults with poor health (eg, severe comorbidities and/or cognitive and functional disability) – Individualized goals for such patients may be even higher (for example, A1C <8.5 percent) and should include efforts to preserve quality of life, avoid hypoglycemia and related complications, and severe hyperglycemia (eg, >350 mg/dL [19.4 mmol/L]). An A1C of 8.5 percent equates to an estimated average glucose of 200 mg/dL (11.1 mmol/L).
●Limitations of A1C measurements – It is important to note that the measurement of A1C may not be accurate in several situations that are seen frequently in older adults. These include anemia and other conditions that impact red blood cell life span, chronic kidney disease, recent transfusions and erythropoietin treatment, recent acute illness or hospitalizations, and chronic liver diseases. Residents of long-term care facilities tend to have higher prevalence of these medical conditions [18]. To assess glycemic control for management in this setting, glucose monitoring with fingersticks and a glucose meter, or continuous glucose monitoring (CGM) in selected patients, may be used (see 'Monitoring of glycemia' below). Biologic and patient-specific factors that may cause misleading A1C results are reviewed separately. (See "Measurements of glycemia in diabetes mellitus", section on 'Unexpected or discordant values' and "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Type 2 diabetes'.)
Avoiding hypoglycemia — Hypoglycemia should be avoided in older adults. Avoidance of hypoglycemia is an important consideration in choosing therapeutic agents and establishing glycemic goals. Insulin secretagogues such as sulfonylurea and meglitinides, as well as all types of insulin, should be used with caution in frail older adults [19]. In particular, older adults beginning a dietary and/or exercise program who are at or close to glycemic goals may need an empiric reduction in the dose of insulin or insulin secretagogues to prevent hypoglycemia. (See 'Choice of second drug' below and "Hypoglycemia in adults with diabetes mellitus", section on 'Strategies to manage hypoglycemia'.)
The vulnerability to hypoglycemia is substantially increased in older adults [1,20]. Older adults may have more neuroglycopenic manifestations of hypoglycemia (dizziness, weakness, delirium, confusion) compared with adrenergic manifestations (tremors, sweating), resulting in delayed recognition of hypoglycemia [19]. These neuroglycopenic symptoms may be missed or misconstrued as primary neurologic disease (such as a transient ischemic attack), leading to underreporting of hypoglycemic episodes by the patients.
Hypoglycemia can result in poor outcomes, such as traumatic falls, adverse cardiovascular events, and cardiac autonomic dysfunction [21,22]. In addition, severe hypoglycemia requiring hospitalization has been associated with an increased risk of developing dementia that is higher in patients with repeated episodes, although the direction of causality, if any, is unknown [23,24].
Even a mild episode of hypoglycemia may lead to adverse outcomes in frail older patients. As an example, episodes of dizziness or weakness increase the risk of falls and fractures.
Cardiovascular risk reduction — Older adults with diabetes are at risk of developing a similar spectrum of macrovascular complications as their younger counterparts with diabetes. However, their absolute risk for CVD is much higher than younger adults [25]. As in younger patients with type 2 diabetes, risk reduction should be focused upon the following areas (see "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus"):
●Smoking cessation
●Treatment of hypertension
●Treatment of dyslipidemia
●Aspirin therapy (when tolerated)
●Exercise
Older patients are likely to derive greater reduction in morbidity and mortality from cardiovascular risk reduction, with treatment of hypertension and lipid lowering with statin therapy, than from tight glycemic control [1,14,26].
Both diabetes and older age are major risk factors for coronary heart disease (CHD). It is therefore not surprising that CHD is by far the leading cause of death in older patients with diabetes. There are few data specifically addressing optimal cardiovascular risk reduction in older patients. Benefits from lipid lowering and blood pressure control have been extracted from trials in older adults with or without diabetes and from trials in patients with diabetes, which included some older adults [1,26]. As with glycemic control, the benefit of cardiovascular risk reduction depends upon the patient's frailty, overall health, and projected period of survival. (See 'Polypharmacy and deintensification' below.)
Smoking cessation — Smoking in patients with diabetes mellitus is an independent risk factor for all-cause mortality, which is due largely to CVD. Despite the absence of any high-quality trial data, smoking cessation should be vigorously promoted. (See "Overview of smoking cessation management in adults".)
Treatment of hypertension — Treatment of hypertension in older patients is clearly beneficial, including in patients over age 80 years. Recommended therapeutic goals and drug options for patients with diabetes and older adults are reviewed in detail elsewhere. (See "Treatment of hypertension in patients with diabetes mellitus" and "Treatment of hypertension in older adults, particularly isolated systolic hypertension".)
Treatment of dyslipidemia — For most older patients with diabetes, we use a statin drug (unless contraindicated) to lower cholesterol. The ACCORD trial found no benefit of adding fenofibrate to statin therapy in patients with diabetes who were at high risk for CVD [27].
The relative beneficial effects of lipid lowering with statins are similar in older and younger patients with diabetes, and the absolute benefit is typically greater in older than in younger patients [28,29]. As with the goal for glycemic control, goals for lipid management should be adjusted based upon older patients' comorbidities, cognitive status, and personal preferences. Reductions in events with statin therapy can occur quickly (within weeks to months), and so even in older patients, such therapy can be expected to reduce events during a patient's expected lifespan. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)
The presence or absence of CVD risk factors other than diabetes should guide the intensity of statin therapy. Dosing based upon risk of CVD is reviewed in detail separately. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Our approach' and "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)
Patients with fasting hypertriglyceridemia (≥500 mg/dL [5.7 mmol/L]) should be evaluated for secondary causes of hypertriglyceridemia. Some patients may require medical therapy to reduce the risk of pancreatitis. The treatment of hypertriglyceridemia is reviewed elsewhere. (See "Hypertriglyceridemia in adults: Management", section on 'Treatment goals'.)
Aspirin — The value of daily aspirin therapy in patients with known macrovascular disease (secondary prevention) is widely accepted (see "Aspirin in the primary prevention of cardiovascular disease and cancer"). A meta-analysis of a large number of secondary prevention trials found that the absolute benefit of aspirin was greatest in those over age 65 years with diabetes or diastolic hypertension [30].
The role of aspirin for the primary prevention of cardiovascular events in patients with diabetes is less certain. These trials and recommendations for aspirin therapy are reviewed elsewhere. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Aspirin'.)
Exercise — The benefits of exercise are reviewed below. (See 'Lifestyle modification' below.)
LIFESTYLE MODIFICATION — The initial treatment of type 2 diabetes in older patients is similar to that in younger patients and includes counseling on nutrition, physical activity, optimizing metabolic control, and preventing complications. Weight reduction (if needed) through diet, exercise, and behavioral modification can be used to improve glycemic control, although the majority of older patients with type 2 diabetes will require medication over the course of their diabetes. (See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Diabetes education'.)
The oldest age group in the Diabetes Prevention Program (DPP; >60 years of age at baseline) had the greatest improvement in glycemia over time, related in part to better adherence to the lifestyle program (a behavioral modification program aimed at a low-fat diet and exercise for 150 minutes per week), compared with the younger age groups [31,32]. These data suggest that older persons can respond well to lifestyle programs. (See "Prevention of type 2 diabetes mellitus", section on 'Lifestyle modification'.)
Lifestyle modification is also beneficial for improving glycemia in older adults with established type 2 diabetes. In one trial, 100 older adults (mean age approximately 72 years) on stable oral or injectable medications for the previous six months were randomly assigned to an intensive lifestyle intervention (diet and exercise to achieve a 10 percent body weight loss) for six months followed by a maintenance phase or a control intervention (monthly educational group sessions) [33]. After one year, the reduction in A1C (mean difference 0.9 percent, 95% CI 0.5-1.2) and body weight (mean difference 8.1 kg, 95% CI 6.1-10.2) was greater in the intensive lifestyle group. Patients assigned to the intensive lifestyle intervention had more episodes of mild hypoglycemia (≥54 to 70 mg/dL [≥3 to 3.9 mmol/L]) than the control group (29 versus 19), underscoring the need to consider empiric reductions in glucose lowering therapy prior to an intensive lifestyle intervention. (See 'Avoiding hypoglycemia' above.)
●Physical activity – Older adults should be encouraged to be as active as their functional status will allow. Functionally independent adults should be encouraged to perform 30 minutes of moderate-intensity aerobic activity (eg, brisk walking) at least five days per week. In sedentary individuals, we stress the importance of gradually increasing activity from current baseline and provide practical guidance on how to do so. For example, walking inside the house five minutes, one to three times a day, to start and building up to the daily goal.
Routine testing by electrocardiogram or cardiac exercise testing is not indicated for most asymptomatic adults prior to initiating moderate physical activity, unless they are at high risk for coronary disease on the basis of multiple risk factors. Patients with deconditioning at risk for falls should be referred to an exercise physiologist and/or physical therapist for muscle strengthening and balance training in a safe environment.
Exercise is beneficial to help maintain physical function, reduce cardiac risk, and improve insulin sensitivity in patients with diabetes. In older adults, exercise also improves body composition and arthritic pain, reduces falls and depression, increases strength and balance, enhances the quality of life, and improves survival [34-37]. Studies of frail older people have shown that weight training should be included in addition to aerobic exercises [38]. (See "Exercise guidance in adults with diabetes mellitus" and "Physical activity and exercise in older adults".)
●Medical nutrition therapy – Medical nutrition therapy (MNT) is the process by which the nutrition prescription is tailored for people with diabetes based upon medical, lifestyle, and personal factors and is an integral component of diabetes management and diabetes self-management education. Most older adults with diabetes should be considered for a medical nutrition evaluation. In a randomized trial of medical nutrition intervention in adults ≥65 years of age, patients in the intervention group had significantly greater improvements in fasting plasma glucose (-18.9 versus -1.4 mg/dL [-1.05 versus -0.08 mmol/L]) and A1C (-0.5 percentage points versus no change) than control patients [39].
Unique challenges with aging, such as altered taste perception, coexisting illnesses and dietary restrictions, compromised dentition, altered gastrointestinal function, impaired food shopping and preparation capabilities, and memory decline leading to skipped meals, should be considered before developing meal plans. In general, it is best to avoid a complex dietary treatment regimen in older adults. (See "Nutritional considerations in type 2 diabetes mellitus", section on 'Medical nutrition therapy'.)
•Obese or overweight older adults with high functional status may benefit from caloric restriction and an increase in physical activity, with a weight loss goal of approximately 5 to 7 percent of body weight [1,40,41].
•Normal-weight older adults require a different dietary prescription. A regular diet with preferred food items may improve quality of life and prevent weight loss. Weight loss is associated with risk of morbidity and mortality in older adults, although separating the effects of intentional from unintentional weight loss has been problematic [42]. Unintentional weight loss in an older adult requires further evaluation. (See "Geriatric nutrition: Nutritional issues in older adults".)
•Older patients with severe comorbidities and/or cognitive or functional disability may benefit from spreading carbohydrates across the day and avoiding a large portion of carbohydrate in any one meal. We avoid strict dietary restrictions for such individuals.
PHARMACOLOGIC THERAPY — There are few data specifically addressing drug therapy in older adults [2,8]. However, most diabetes drug trials, including cardiovascular outcomes trials, included a wide range of patients with type 2 diabetes, including those >65 years of age. Thus, the approach to choosing initial, alternative, and combination therapy is similar in older and younger adults. All of the types of oral hypoglycemic drugs and insulin are effective in older patients, although each has some limitations (table 2). In general, oral and injectable agents with low risk of hypoglycemia are preferred in older adults.
Choice of initial drug — We suggest metformin as initial therapy for older adults who do not have contraindications to its use (eg, kidney impairment [estimated glomerular filtration rate (eGFR) <30 to <45 mL/min/1.73 m2] or unstable or acute heart failure at risk of hypoperfusion and hypoxemia), along with lifestyle modification aimed at weight loss for the majority of patients who are overweight or obese. (See 'Metformin' below and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Choice of initial therapy'.)
Insulin can also be considered as initial therapy for patients with type 2 diabetes, particularly those presenting with A1C >9 percent (74.9 mmol/mol), fasting plasma glucose >250 mg/dL (13.9 mmol/L), random glucose consistently >300 mg/dL (16.7 mmol/L), or ketonuria. Because of concern for hypoglycemia, some clinicians use insulin only for a short time to ameliorate glucose toxicity (transient suppression of beta cell function and increased insulin resistance from chronic exposure to very high concentrations of glucose). Once insulin secretion and sensitivity are improved, the dose can be lowered or replaced with metformin or another glucose-lowering agent with lower risk of hypoglycemia. (See "Insulin therapy in type 2 diabetes mellitus".)
Our suggestions are based upon clinical trial evidence and clinical experience in achieving glycemic targets and minimizing adverse effects, with the recognition that there is a paucity of many high-quality, head-to-head drug comparison trials and trials with important clinical endpoints, such as effects on complications [43]. The long-term benefits and risks of using one approach over another are unknown. Pharmacologic therapy must be individualized based upon patient abilities and comorbidities. "Start low and go slow" is a good principle to follow when starting any new medications in an older adult.
Metformin
●When to initiate therapy – For most older adults, we suggest metformin as initial therapy (see 'Choice of initial drug' above). Metformin is an attractive agent to use in older adults due to a low risk of hypoglycemia. Healthy older adults may be treated similarly as younger adults with initiation of metformin at the time of diabetes diagnosis, even if the presenting A1C is below the individualized medication-treated target. It is likely that metformin will safely reduce glycemia at any level and may either reduce progression of hyperglycemia or reduce the likelihood that a patient will develop diabetes-related complications [44]. However, for patients who present with A1C near their medication-treated target and who prefer to avoid medication, or in whom there are multiple comorbidities and concerns about polypharmacy, a three- to six-month trial of lifestyle modification before initiating metformin is reasonable.
●Dosing – Renal function, weight loss, and gastrointestinal side effects may be limiting factors in older adults taking metformin. We typically begin with 500 mg daily and increase the dose slowly over several weeks to minimize gastrointestinal side effects. Extended-release formulation of metformin may be tolerated better in those who are unable to tolerate immediate-release metformin due to gastrointestinal side effects.
For a patient with an eGFR ≥45 mL/min/1.73 m2, we titrate up to full dose. For patients with an eGFR of 30 to 45 mL/min/1.73 m2, we typically reduce the maximum metformin dose by half (no more than 1000 mg per day). While these recommendations are reasonable, there are few studies to establish the therapeutic efficacy or safety with these reduced doses. Continuing metformin treatment is contraindicated when eGFR reaches 30 mL/min/1.73 m2 or less. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Dosing'.)
●Precautions – Older patients also are at increased risk for developing conditions other than diabetes that reduce kidney function further or cause lactic acidosis (eg, acute infections, myocardial infarction [MI], stroke, cardiac failure,). Therefore, metformin should be used with caution in older patients. Any older patient treated with metformin should be cautioned to stop taking the drug immediately if they become seriously ill for any reason or if they are to undergo a procedure requiring the use of iodinated contrast material. In addition, kidney function (measurement of serum creatinine and eGFR) should be monitored every three to six months, rather than annually. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)
Contraindications to metformin — For most patients with contraindications and/or intolerance to metformin, 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. This approach is reviewed in detail separately. (See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Contraindications to or intolerance of metformin' and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Established cardiovascular or kidney disease' and "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease".)
PERSISTENT HYPERGLYCEMIA — After a successful initial response to oral therapy, many patients fail to maintain target A1C levels.
Evaluation — If glycemic goals are not met with a single agent, the older patient should be evaluated for contributing causes similar to younger adults, such as difficulty adhering to the medication, side effects, or poor understanding of the nutrition plan [1,8]. In addition, older adults should also be assessed for age-related barriers, such as cognitive and/or functional decline, depression, and other social and financial issues that might be interfering with self-care. If glycemic control is still above the individualized target, an additional agent is needed. In older patients who require more than one agent, pill-dosing dispensers may help improve adherence. As an alternative, family members or caregivers may be required to help administer medication.
Choice of second drug — For older patients who have persistent hyperglycemia above their individualized glycemic target despite treatment with lifestyle intervention and metformin, a second agent should be selected. The choice of a second agent should be individualized based upon efficacy, the patient's underlying comorbidities, risk of hypoglycemia, the impact on weight, side effects, and cost (figure 1). (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Indications for a second agent' and "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Our approach'.)
Medication concerns specifically related to adults >65 years are reviewed below. The individual agents are discussed in more detail in the individual topic reviews. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus" and "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus" and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of type 2 diabetes mellitus" and "Alpha-glucosidase inhibitors for treatment of diabetes mellitus".)
Severe or symptomatic hyperglycemia — Insulin is often preferred in those with A1C >9 percent (74.9 mmol/mol) or with persistent symptomatic hyperglycemia. Insulin is sometimes underutilized in older adults because of fear (by the clinician, patient, or family) that it is too complicated or dangerous. Addition of once-daily basal insulin to a non-insulin agent (usually metformin) is a low-complexity regimen with a relatively lower risk of hypoglycemia compared with regimens using multiple insulin doses [45].
Before beginning insulin therapy, it is important to evaluate whether or not the patient is physically and cognitively capable of using an insulin pen or drawing up and giving the appropriate dose of insulin (using syringes and vials), monitoring blood glucose, and recognizing and treating hypoglycemia. For older patients taking a fixed daily dose of insulin and who are capable of giving the insulin shot but not of drawing it up, a pharmacist or family member may prepare a week's supply of insulin in syringes and leave them in the refrigerator. Such a plan may allow an older patient to remain living independently at home.
●We typically start with long-acting insulin (10 units or 0.2 units per kg) in the morning. This is because older adults tend to have higher contribution of postprandial hyperglycemia compared with fasting hyperglycemia at all A1C levels [46].
●The dose of the long-acting insulin can be adjusted once weekly to reach the target fasting blood glucose.
●Insulin should be carefully titrated to avoid hypoglycemia and its consequences. (See 'Avoiding hypoglycemia' above.)
●Insulin metabolism is altered in patients with chronic kidney failure, so that less insulin is needed when the glomerular filtration rate (GFR) is below 50 mL/min/1.73 m2. (See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Treatment'.)
Specifics of insulin therapy are discussed in detail elsewhere. (See "General principles of insulin therapy in diabetes mellitus" and "Insulin therapy in type 2 diabetes mellitus".)
History of cardiorenal disease — Sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin or canagliflozin) or glucagon-like peptide 1 (GLP-1) receptor agonists (liraglutide or semaglutide) are reasonable second agents for patients with established cardiorenal disease [47,48]. All of these drugs have a low risk of hypoglycemia on their own or in combination with other drugs that do not usually cause hypoglycemia. GLP-1 receptor agonists should be titrated slowly, monitoring for gastrointestinal (GI) side effects, which could precipitate dehydration and acute kidney injury (AKI). 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. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'.)
Avoidance of hypoglycemia — In older adults at increased risk of hypoglycemia, GLP-1 receptor agonists, SGLT2 inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors are options as they are associated with a low hypoglycemia risk. DPP-4 inhibitors are useful only to improve mild hyperglycemia since they are relatively weak agents and usually lower A1C levels by only 0.6 percent. However, in frail older adult patients with late-onset diabetes, particularly patients at high risk of hypoglycemia and hypoglycemia unawareness, a DPP-4 inhibitor can be a useful agent to lower glycemia to the individualized target. (See "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy'.)
Avoidance of weight gain — GLP-1 receptor agonists may be appropriate to use when avoidance of weight gain is a primary consideration and cost is not a major barrier. SGLT2 inhibitors are also associated with weight loss. However, in the absence of cardiovascular disease (CVD), the risks of SGLT2 inhibitors in older individuals (eg, dehydration, falls, fractures) may outweigh the benefits. DPP-4 inhibitors, which are weight neutral, also may be a reasonable option.
Cost concerns — If cost is a concern, adding a short- or intermediate-acting sulfonylurea with a relatively lower rate of hypoglycemia, such as glipizide, glimepiride, or gliclazide (gliclazide not available in the United States), remains a reasonable alternative. Choosing a sulfonylurea balances glucose-lowering efficacy, universal local availability, and low cost with risk of hypoglycemia and weight gain. Short- or intermediate-acting sulfonylureas can also be used cautiously in patients with renal insufficiency when other classes are contraindicated. Generic pioglitazone is also inexpensive. However, we tend not to use pioglitazone in older adults, due the risks of fluid retention; weight gain; and increased risks of heart failure, macular edema, and osteoporotic fracture. (See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety'.)
A typical starting dose of a sulfonylurea is as follows (see "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Dosing and monitoring'):
●Glipizide – 2.5 mg taken 30 minutes before breakfast
●Glimepiride – 1 mg taken with breakfast or the first main meal
●Gliclazide (immediate release) – 40 mg once daily (one-half of an 80 mg tablet)
In patients who are using sulfonylurea drugs, the presence and frequency of hypoglycemia should be evaluated at each visit. All self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) data that are available should be reviewed and the frequency and details of any recognized episodes of hypoglycemia determined. In older adults with A1C <7 percent, unrecognized hypoglycemia should be carefully evaluated. (See 'Monitoring of glycemia' below and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia'.)
The reported frequency of sulfonylurea-related hypoglycemia in older adults is variable. In general, hospitalization rates for hypoglycemia are higher among older (>75 years) versus younger (65 to 74 years) patients with diabetes [49]. In an analysis of adverse event data from a drug surveillance project, oral hypoglycemic agents accounted for 10 percent of hospitalizations for adverse drug events [50].
It is best to avoid the use of long-acting sulfonylureas (eg, glyburide) in older adults due to higher risk of hypoglycemia, especially individuals who are inconsistent in their meals or have cognitive decline that prevents prompt recognition or treatment of hypoglycemic episodes [51]. Drug-induced hypoglycemia is most likely to occur in the following circumstances in older patients and may be a limiting factor for use of these drugs in older adults:
●After exercise or missed meals
●With alcohol abuse
●When they have impaired kidney or cardiac function or intercurrent gastrointestinal disease
●During therapy with salicylates, sulfonamides, fibric acid derivatives (such as gemfibrozil), and warfarin [52]
●After being in the hospital [53]
These issues may arise when there is a change in overall health status in older adults with diabetes.
Dual agent failure — For patients who do not achieve A1C goals with two agents (eg, metformin plus sulfonylurea or another agent), we suggest starting or intensifying insulin therapy (see "Insulin therapy in type 2 diabetes mellitus", section on 'Designing an insulin regimen'). In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally tapered and discontinued, while metformin is continued. Another option is two oral agents and a GLP-1 receptor agonist.
It is reasonable to try a GLP-1 agonist before starting insulin in patients who are close to glycemic goals, who prefer not to start insulin, and in whom weight loss or avoidance of hypoglycemia is a primary consideration. Once-weekly formulation of GLP-1 agonist is particularly attractive for patients and their caregiver. Three oral agents (eg, metformin, sulfonylurea, and a DPP-4 inhibitor) can be considered in patients with A1C values that are not too far from goal (A1C ≤8.5 percent). However, this option is more expensive and contributes to the problem of polypharmacy in older adults (see 'Polypharmacy and deintensification' below). The management of persistent hyperglycemia is reviewed in more detail separately. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Dual agent failure'.)
Polypharmacy and deintensification — Use of multiple drugs is common in older adults. Management of hyperglycemia and its associated risk factors often increases the number of medications even more in the older adult with diabetes. Side effects may exacerbate comorbidities and impede patients' ability to manage their diabetes. Therefore, the medication list should be kept current and reviewed at each visit [1,8]. Overtreatment and complicated regimens should be avoided. When older patients present with complex regimens that may have been required in the past, they can often be simplified to be consistent with the modified glycemic targets of an older patient [54,55]. (See 'Controlling hyperglycemia' above.)
MONITORING OF GLYCEMIA — Monitoring is usually necessary to determine the overall efficacy of diabetes management.
●Glycated hemoglobin (A1C) – We typically monitor A1C twice yearly in older patients who are meeting treatment goals and who have stable glycemic control, and quarterly in patients whose therapy has changed or who are not meeting their glycemic goals. It is important to look for any conditions that interfere with A1C measurement (eg, anemia, recent infections, kidney failure, erythropoietin therapy, etc). In this setting or when there are unexpected or discordant A1C values, medication adjustments should be based on glucose readings rather than A1C. (See "Measurements of glycemia in diabetes mellitus", section on 'Glycated hemoglobin (A1C)'.)
●Self-monitoring of blood glucose (SMBG) – Blood glucose concentrations can be monitored at home by the patient or a caregiver in the following settings [1,8]:
•SMBG is helpful in older patients with type 2 diabetes who take medications that can cause hypoglycemia (eg, insulin or sulfonylureas).
•SMBG is necessary in older patients with type 2 diabetes treated with complex insulin regimens.
•SMBG may also be useful for some patients who would take action to modify eating patterns or exercise, as well as be willing to intensify pharmacotherapy, based on SMBG results.
However, infrequent (or no) SMBG may be adequate for older patients with type 2 diabetes who are diet treated or who are treated with oral agents not associated with hypoglycemia. The effectiveness of SMBG in terms of improving glycemic control in patients with type 2 diabetes is less clear than for type 1 diabetes. (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Type 2 diabetes'.)
●Continuous glucose monitoring (CGM) – Advances in CGM have made it possible to use the technology in older and even frail patients. Professional CGM devices, applied like a patch on a patient's arm, measure interstitial glucose levels every 5 to 15 minutes for 10 to 14 days. These devices provide patterns of glucose excursions that can be the foundation for choosing or adjusting insulin doses in patients on multiple daily insulin regimens. These CGM devices are covered by Medicare in qualifying patients. (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'.)
SCREENING FOR MICROVASCULAR COMPLICATIONS — Older adults with diabetes are at risk of developing a similar spectrum of microvascular complications as their younger counterparts with diabetes. Retinopathy, nephropathy, and foot problems are all important complications of diabetes mellitus in older patients. Monitoring recommendations for older patients with diabetes are similar to those in younger patients (table 3). In particular, complications that impair functional capacity (eg, retinopathy, foot problems) should be identified and treated promptly [2].
Retinopathy — The prevalence of retinopathy increases progressively with increasing duration of diabetes (figure 2). (See "Diabetic retinopathy: Classification and clinical features".)
Regular eye examinations are extremely important for older diabetic patients because poor vision can lead to social isolation, an increased risk of accidents, and impaired ability to measure blood glucose and draw up insulin doses. A complete ophthalmologic examination should be performed by a qualified ophthalmologist or optometrist at the time of diagnosis and at least yearly thereafter. The purpose is to screen not only for diabetic retinopathy, but also for cataracts and glaucoma, which are approximately twice as common in older diabetic compared with nondiabetic individuals [56,57]. (See "Diabetic retinopathy: Screening".)
Nephropathy — The availability of effective therapy for diabetic nephropathy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockade agents (ARBs) has led to the recommendation that all patients with diabetes be screened for increased urinary albumin excretion annually. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus" and "Moderately increased albuminuria (microalbuminuria) in type 2 diabetes mellitus".)
However, the prevalence of increased urinary albumin excretion increases in the older population for reasons unrelated to diabetic nephropathy. For older patients who are already taking an ACE inhibitor or ARB, it may not be necessary or helpful to continue testing for increased urinary albumin excretion on an annual basis.
Foot problems — Foot problems are an important cause of morbidity in patients with diabetes, and the risk of them is much higher in older patients. Both vascular and neurologic disease contribute to foot lesions. It is estimated, for example, that the prevalence of diabetic neuropathy in patients with type 2 diabetes is 32 percent overall and more than 50 percent in patients over age 60 years [58,59]. (See "Management of diabetic neuropathy".)
In addition to the increasing prevalence of neuropathy with age, more than 30 percent of older diabetic patients cannot see or reach their feet, and they may therefore be unable to perform routine foot inspections.
We recommend that older diabetic patients have their feet examined at every visit; this examination should include an assessment of the patient's ability to see and reach his or her feet and inquiry about other family members or friends who could be trained to do routine foot inspections. Visits to a podiatrist on a regular basis should also be considered. A detailed neurologic examination and assessment for peripheral artery disease should be performed at least yearly. It is also important that prophylactic advice on foot care be given to any patient whose feet are at high risk. (See "Evaluation of the diabetic foot".)
COMMON GERIATRIC SYNDROMES ASSOCIATED WITH DIABETES — Older adults with diabetes suffer excess morbidity, multimorbidities, and mortality compared with older individuals without diabetes [25]. In addition, they are at high risk for polypharmacy, functional disabilities, and other common geriatric syndromes that include cognitive impairment, depression, urinary incontinence, falls, and persistent pain [1]. Screening for geriatric syndromes may be beneficial in selected patients, particularly when identification and treatment may help achieve more appropriate glycemic goals and/or better glycemic control. (See "Comprehensive geriatric assessment".)
In particular, cognitive function and the possibility of depression should be assessed in older diabetic patients when there is (see "Evaluation of cognitive impairment and dementia" and "Screening for depression in adults"):
●Nonadherence with therapy
●Frequent episodes of hypoglycemia or extreme glucose excursions
●Deterioration of glycemic control without obvious explanation
SPECIAL POPULATIONS
Nursing home patients — There are few studies focusing on management of older adults with diabetes residing in nursing homes [6]. Life expectancy, quality of life, severe functional disabilities, and other coexisting conditions affect goal setting and management plans. (See 'Controlling hyperglycemia' above and 'Avoiding hypoglycemia' above.)
Treatment regimens should be chosen with a focus on avoidance of hypoglycemia and control of hyperglycemic symptoms [18]. For patients requiring insulin, metformin combined with once-daily basal insulin is an effective, relatively simple regimen. If prandial insulin is necessary, it can be administered immediately after a meal to better match the meal size and minimize hypoglycemia. Sliding scale insulin should not be used as a sole means of providing insulin. If a patient is temporarily managed with a sliding scale, a decision should be made within a couple of days about a more physiologic glucose control strategy (table 4).
End-of-life care — Management of patients with diabetes at the end of life must be tailored to individual needs and the severity of the illness. In general, the risks and consequences of hypoglycemia are greater than those of hyperglycemia in patients at the end of life. The goal is to avoid extreme hyperglycemia and dehydration as well as excessive treatment burden such as multiple insulin injections or intensive monitoring.
For patients with type 2 diabetes who are no longer taking anything by mouth, discontinuation of diabetes medications is reasonable [60]. (For patients with type 1 diabetes, continuing a small amount of basal insulin is required to prevent iatrogenic acute hyperglycemia and ketoacidosis.) (See "Palliative care: The last hours and days of life", section on 'Eliminating non-essential medications'.)
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".)
SUMMARY AND RECOMMENDATIONS
●The overall goals of diabetes management in older adults are similar to those in younger adults and include management of both hyperglycemia and risk factors. (See 'Goals' above.)
●Older adults with diabetes are a heterogeneous population that includes persons residing independently in communities, in assisted care facilities, or in nursing homes. They can be fit and healthy, or frail with many comorbidities and functional disabilities. The appropriate target for glycated hemoglobin (A1C) should be individualized based on overall health and life expectancy, as well as on identified patient-specific risks for hypoglycemia and the ability of the patient to adopt and adhere to specific treatment regimens (table 1). (See 'Controlling hyperglycemia' above.)
●The vulnerability to hypoglycemia is substantially increased in older adults. Thus, avoidance of hypoglycemia is an important consideration in establishing goals and choosing therapeutic agents in older adults. (See 'Avoiding hypoglycemia' above and "Hypoglycemia in adults with diabetes mellitus", section on 'Strategies to manage hypoglycemia'.)
●Older patients are more likely to derive greater relative reduction in morbidity and mortality from cardiovascular risk reduction, particularly treatment of hypertension and lipid lowering with statin therapy, than from tight glycemic control. (See 'Cardiovascular risk reduction' above.)
●Older patients with diabetes should receive individualized counseling regarding lifestyle modification, including a medical nutrition evaluation and exercise counseling. The nutrition prescription is tailored for older people with diabetes based upon medical, lifestyle, and personal factors. Exercise is beneficial to help maintain physical function, reduce cardiac risk, and improve body composition and insulin sensitivity in older patients with diabetes. (See 'Lifestyle modification' above.)
●In the absence of specific contraindications, we suggest metformin as initial therapy for older patients with diabetes (Grade 2B). Insulin can also be considered a first-line therapy for patients with type 2 diabetes, particularly patients presenting with A1C >9 percent (74.9 mmol/mol), fasting plasma glucose >250 mg/dL (13.9 mmol/L), random glucose consistently >300 mg/dL (16.7 mmol/L), or ketonuria. Because of concern for hypoglycemia, some clinicians use insulin only for a short time to ameliorate glucose toxicity. Once insulin secretion and sensitivity are improved, it may be possible to lower the dose or replace insulin with metformin or another oral hypoglycemic agent with lower risk of hypoglycemia. (See 'Choice of initial drug' above.)
●For fit older patients, we suggest initiating metformin at the time of diabetes diagnosis (along with consultation for lifestyle intervention), even if the presenting A1C is below the individualized medication-treated target (Grade 2C). It is likely that metformin will safely reduce glycemia at any level and may either reduce progression of hyperglycemia or reduce the likelihood that a patient will develop diabetes-related complications. (See 'Metformin' above.)
An alternative option for patients who present with A1C near their medication-treated target and who prefer to avoid medication is a three- to six-month trial of lifestyle modification before initiating metformin.
●For patients with contraindications and/or intolerance to metformin, we choose an alternative glucose-lowering medication guided initially by patient comorbidities, and in particular, the presence of atherosclerotic cardiovascular disease (ASCVD) or albuminuric chronic kidney disease. The approach to choosing alternative therapy in metformin-intolerant patients is similar in older and younger adults. (See 'Contraindications to metformin' above and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Contraindications to or intolerance of metformin'.)
●For older patients who have persistent hyperglycemia above their individualized glycemic target despite treatment with lifestyle intervention and metformin, a second agent should be selected. The therapeutic options for patients who fail initial therapy with lifestyle intervention and metformin are similar in older and younger patients. All of the medications have advantages and disadvantages (table 2). The choice of a second agent should be individualized based upon efficacy, risk of hypoglycemia, the patient's underlying comorbidities, the impact on weight, side effects, and cost (figure 1). (See 'Persistent hyperglycemia' above and "Management of persistent hyperglycemia in type 2 diabetes mellitus".)
●For patients who do not achieve A1C goals with two agents (eg, metformin plus sulfonylurea or another agent), we suggest adding basal insulin therapy (Grade 2B). Another option is two oral agents and a glucagon-like peptide 1 (GLP-1) receptor agonist. In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally tapered and discontinued, while metformin is continued. (See 'Dual agent failure' above.)
●Older adults with diabetes are at risk of developing a similar spectrum of microvascular complications as their younger counterparts with diabetes. Monitoring recommendations for older patients with diabetes are similar to those in younger patients (table 3). In particular, complications that impair functional capacity (eg, retinopathy, foot problems) should be identified and treated promptly. (See 'Screening for microvascular complications' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David McCulloch, MD, who contributed to earlier versions of this topic review.
