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Treatment of type 2 diabetes mellitus in the older patient
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Treatment of type 2 diabetes mellitus in the older patient
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: May 09, 2016.

INTRODUCTION — The prevalence of type 2 diabetes continues to increase steadily as more people live longer and grow heavier. From 1995 to 2004, the overall prevalence of type 2 diabetes in nursing home residents increased from 16 to 23 percent [1].

Older adults with diabetes are at risk of developing a similar spectrum of macrovascular and microvascular complications as their younger counterparts with diabetes. In addition, they are at high risk for polypharmacy, functional disabilities, and common geriatric syndromes that include cognitive impairment, depression, urinary incontinence, falls, and persistent pain [2].

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 medical care in adults with diabetes mellitus" and "Initial management of blood glucose in adults with type 2 diabetes mellitus" and "Management of persistent hyperglycemia in type 2 diabetes mellitus".)

TREATMENT GOALS — 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. 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. Thus, management of diabetes in older adults should be individualized, taking into account these variables.

In frail older patients with diabetes, avoidance of hypoglycemia, hypotension, and drug interactions due to polypharmacy are of even greater concern than in younger patients with diabetes [3]. In addition, management of coexisting medical conditions is important, as it influences their ability to perform self-management.

Glycemic targets — There are few data specifically addressing optimal glycemic goals in medication-treated older patients [4,5]. Goals for glycemic control, as well as risk factor management, should be based upon the individual's overall health and projected period of survival, since the risk of complications is duration-dependent. The appropriate target for glycated hemoglobin (A1C) in fit older patients who have a life expectancy of over 10 years should be individualized based on the factors above, on identified patient-specific risks for hypoglycemia, and on the ability of the patients to adopt and adhere to specific treatment regimens.

In the absence of any long-term clinical trial data in fit older populations, 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) [6].

The glycemic goal should be somewhat higher (A1C ≤8.0 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 and functional comorbidities and in those whose life expectancy is less than 10 years.

Individualized goals for the very old may be even higher (A1C <8.5 percent) and should include efforts to preserve quality of life and avoid hypoglycemia and related complications. An A1C of 8.5 percent equates to an estimated average glucose of 200 mg/dL (11.1 mmol/L).

These goals are consistent with the American Geriatrics Society (AGS), the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Diabetes Working Party guidelines [2,7-11]. (See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Glycemic targets'.)

Hyperglycemia increases dehydration, impairs vision and cognition, and increases risk of infections [12], all of which contribute to functional decline and an increased risk of falling in older diabetic patients. 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 (GFRs) and lower load of glucose delivered to the tubules for reabsorption. Furthermore, side effects of diabetes treatment, most notably hypoglycemia, can result in poor outcomes, such as traumatic falls and exacerbation of comorbid conditions. The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial suggest that intensive therapy in persons at high risk for cardiovascular disease (CVD), and especially with polypharmacy, may increase the risk for both total and CVD mortality [13]. Whether glycemia is the cause of the increased mortality is unclear.

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 infusions, recent acute illness or hospitalizations, and chronic liver diseases. Biological and patient-specific factors that may cause misleading A1C results are reviewed separately. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Glycated hemoglobin'.)

Avoiding hypoglycemia — The vulnerability to hypoglycemia is substantially increased in older adults [2,14]. 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 [15]. These neuroglycopenic symptoms may be missed or misconstrued as primary neurologic disease (such as a transient ischemic attack), leading to inappropriate reporting of hypoglycemic episodes by the patients.

Hypoglycemic episodes in older individuals may also increase the risk of adverse cardiovascular events and cardiac autonomic dysfunction [16,17]. 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 [18,19].

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 fracture leading to nursing home placement.

Given the risks, avoidance of hypoglycemia is an important consideration in choosing therapeutic agents and establishing glycemic goals in older adults. Insulin secretagogues such as sulfonylurea and meglitinides, as well all types of insulin, should be used with caution in frail older adults [15]. (See "Management of hypoglycemia during treatment of diabetes mellitus", section on 'Strategies to prevent hypoglycemia'.)

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. Older adults with diabetes suffer excess morbidity and mortality compared with older individuals without diabetes [20].

Both diabetes and 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 [2]. As with glycemic control, the benefit of cardiovascular risk reduction depends upon the patient’s frailty, overall health, and projected period of survival. Older patients are more likely to derive greater reduction in morbidity and mortality from cardiovascular risk reduction, particularly lipid lowering with statin therapy, than from tight glycemic control [2,13]. As reviewed above, the results of the ACCORD trial suggest that intensive glycemic therapy in persons at high risk for cardiovascular disease, and especially with polypharmacy, may increase the risk for both total and CVD mortality [13].

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 diabetes mellitus"):

Smoking cessation

Treatment of hypertension

Treatment of dyslipidemia

Aspirin therapy

Exercise

Smoking cessation — Smoking in patients with diabetes mellitus is an independent risk factor for all-cause mortality, due largely to CVD. Therefore, 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 the elderly patient, particularly isolated systolic hypertension".)

Treatment of dyslipidemia — For most older patients with diabetes, we recommend use of 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 [21].

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 than in younger patients [22,23]. As with the goal for glycemic control, however, goals for lipid management should be adjusted based upon older patients' life expectancy, 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 "Treatment of dyslipidemia in the older adult".)

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 "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease", section on 'Medication choice strategy' and "Treatment of lipids (including hypercholesterolemia) in primary prevention", section on 'Dose'.)

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 "Approach to the patient with hypertriglyceridemia", section on 'Management'.)

Aspirin — The value of daily aspirin therapy in patients with known macrovascular disease (secondary prevention) is widely accepted (see "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease"). 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 [24].

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 medical care in adults with diabetes mellitus", section on 'Aspirin'.)

Exercise — 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 [25-28]. Studies of frail older people have shown that weight training should be included in addition to aerobic exercises [29]. 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. (See 'Lifestyle modification' below and "Effects of exercise in adults with diabetes mellitus".)

INITIAL TREATMENT OF HYPERGLYCEMIA — The initial treatment of type 2 diabetes in older patients is similar to that in younger patients and includes instruction on nutrition, physical activity, optimizing metabolic control, and preventing complications. Weight reduction 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 blood glucose in adults with type 2 diabetes mellitus", section on 'Diabetes education'.)

For fit older adults, metformin (in the absence of contraindications) should be initiated at the time of diabetes diagnosis. For patients who prefer to avoid medication and who have a glycated hemoglobin (A1C) near their individualized target, a three to six-month trial of lifestyle modification before initiating metformin is reasonable. For patients with contraindications and/or intolerance to metformin, we suggest a short-acting sulfonylurea (eg, glipizide) as an alternative option. (See 'Drug therapy' below.)

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 International Diabetes Federation (IDF), and the European Diabetes Working Party guidelines [2,7-11,30,31].

Lifestyle modification — All older patients with diabetes should receive counselling about lifestyle modification (exercise, diet, behavioral modification, and weight reduction [if needed]). 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 [32,33]. These data suggest that older persons can respond well to lifestyle programs. (See "Prevention of type 2 diabetes mellitus", section on 'Lifestyle modification'.)

Physical activity – Physical activity benefits people of all ages and may decrease all-cause morbidity and increase lifespan. 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. 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. (See "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. 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 [34]. Thus, most older adults with diabetes should be considered for a medical nutrition evaluation. However, 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 complex dietary and treatment regimen in older adults. (See "Nutritional considerations in type 2 diabetes mellitus", section on 'Medical nutrition therapy'.)

The choice of diet has important clinical considerations:

Obese older adults with diabetes may benefit from caloric restriction and an increase in physical activity with a weight loss goal of approximately 5 percent of body weight [2,35].

Older adults are as much at risk for undernutrition as for obesity. Weight loss increases the risk of morbidity and mortality in older adults [36]. Thus, unintentional weight loss in an older adult requires further evaluation and a different dietary prescription. (See "Approach to the patient with unintentional weight loss".)

Drug therapy — For older patients who do not have contraindications to metformin (eg, renal impairment or unstable or acute heart failure), we suggest metformin as initial therapy, along with lifestyle modification aimed at weight loss for the majority of patients who are overweight or obese. Fit 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 [37]. 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.

Insulin can also be considered as initial therapy for all 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.

There are few data specifically addressing drug therapy in older patients [8,10,38]. However, most diabetes drug trials included a wide range of patients, including those >65 years of age. All of the types of oral hypoglycemic drugs and insulin are safe in older patients, although each has some limitations (table 1). In general, oral and injectable agents with low risk of hypoglycemia are preferred in older adults. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus", section on 'Choice of initial therapy'.)

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 [39]. 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 — For most older adults, we suggest metformin as initial therapy. Metformin is an attractive agent to use in older adults due to a low risk of hypoglycemia. A calculated (or estimated) glomerular filtration rate (GFR) >30 mL/min has been suggested as a safe level of kidney function for the use of metformin. For a patient with an estimated GFR (eGFR) ≥60 mL/min, we prescribe full dose. For patients with an eGFR between 30 and 60 mL/min, we typically reduce the metformin dose by half (no more than 1000 mg per day). Weight loss and gastrointestinal side effects may be limiting factors in older adults taking metformin. Therefore, we typically begin with 500 mg daily and increase the dose slowly over several weeks to minimize gastrointestinal side effects. While the recommendations above are reasonable, there are few studies to establish the therapeutic efficacy or safety with these reduced doses.

Older patients also are at increased risk for developing other conditions that reduce renal function further or cause lactic acidosis (eg, myocardial infarction [MI], stroke, cardiac failure, pneumonia). 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 ill for any reason or if they are to undergo a procedure requiring the use of iodinated contrast material. In addition, renal 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 patients with contraindications and/or intolerance to metformin, we suggest a short-acting sulfonylurea (eg, glipizide). Other options include repaglinide, dipeptidyl peptidase 4 (DPP-4) inhibitors, or insulin. The choice of therapy should be individualized based upon patient characteristics, preferences, and costs. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus".)

Sulfonylureas — For patients with contraindications and/or intolerance to metformin, we suggest a short-acting sulfonylurea (eg, glipizide) for initial therapy. The choice of sulfonylurea balances glucose-lowering efficacy, universal local availability, and low cost with risk of hypoglycemia and weight gain. Sulfonylurea drugs are usually well tolerated. Hypoglycemia is the most common side effect and is more common with long-acting sulfonylurea drugs (eg, chlorpropamide, glyburide, and glimepiride), especially in older adults, in whom severe, prolonged hypoglycemia can develop. Thus, we avoid the use of long-acting sulfonylureas in older adults. We prefer to use a short-acting sulfonylurea such as glipizide. A typical starting dose is 2.5 mg of glipizide taken 30 minutes before breakfast. (See "Sulfonylureas and meglitinides in the treatment of diabetes mellitus" and "Management of hypoglycemia during treatment of diabetes mellitus", section on 'Type 2 diabetes'.)

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 [40]. 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 [41]. In an observational study, the frequency of hypoglycemia in patients over age 65 years treated with either glyburide or chlorpropamide was similar (16.6 episodes per 1000 person-years) [42]. In another study of 52 older patients treated with glyburide or the glipizide gastrointestinal therapeutic system (GITS), no episodes of hypoglycemia occurred during a 23-hour fast [43].

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

When they eat poorly or abuse alcohol

When they have impaired renal or cardiac function or intercurrent gastrointestinal disease

During therapy with salicylates, sulfonamides, fibric acid derivatives (such as gemfibrozil), and warfarin [44]

After being in the hospital [42]

These issues may arise when there is a change in overall health status in older adults with diabetes. In patients who are using sulfonylurea drugs, the presence and frequency of hypoglycemia should be evaluated at each visit.

Other drugs — Other drugs that are sometimes used as initial therapy in older adults include repaglinide, DPP-4 inhibitors, or insulin. 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 "Thiazolidinediones in the treatment of diabetes mellitus", section on 'Safety'.)

Repaglinide and nateglinide are short-acting glucose-lowering drugs that act similarly to the sulfonylureas and have similar or slightly less efficacy in decreasing glycemia. They require more frequent administrations with meals than sulfonylureas and are more expensive. Meglitinides are pharmacologically distinct from sulfonylureas and may be used in patients who have allergy to sulfonylurea medications. They have a similar risk for weight gain as sulfonylureas but possibly less risk of hypoglycemia [45].

Unlike nateglinide, repaglinide is principally metabolized by the liver, with less than 10 percent renally excreted. Dose adjustments with repaglinide do not appear to be necessary in patients with renal insufficiency. In addition, repaglinide is somewhat more effective in lowering A1C than nateglinide. Thus, repaglinide could be considered as initial therapy in a patient with chronic kidney disease who is intolerant of metformin and sulfonylureas. (See "Sulfonylureas and meglitinides in the treatment of diabetes mellitus" and "Management of hyperglycemia in patients with type 2 diabetes and pre-dialysis chronic kidney disease or end-stage renal disease".)

DPP-4 inhibitors are once-a-day oral agents with no risk of hypoglycemia and are weight-neutral, when used as monotherapy, and therefore may be attractive agents to use in older adults. Since they are relatively weak agents and usually lower A1C levels by only 0.6 percent, DPP-4 inhibitors should only be used as monotherapy when the A1C level is relatively close to the goal level.

In a 52-week trial comparing alogliptin with glipizide in 441 older patients with type 2 diabetes (mean age 70 years) inadequately controlled on diet and exercise alone (mean A1C approximately 7.5 percent), the mean reduction in A1C was similar (-0.13 and -0.11 percentage points with alogliptin and glipizide, respectively) [46]. There were fewer hypoglycemic episodes in the alogliptin group (31 versus 232 episodes with glipizide). The reduction in A1C with either drug was lower than what has been reported in previous trials, possibly related to the high dropout rate (40 percent). For patients who completed the trial, the reduction in A1C was -0.42 and -0.33 percent for alogliptin and glipizide, respectively.

Although DPP-4 inhibitors do not cause hypoglycemia or weight gain, the long-term safety with this class of drug has not been established, and they are relatively expensive (four to fivefold more expensive than sulfonylureas). In addition, in one trial comparing saxagliptin with placebo as add-on therapy to metformin, sulfonylureas, or insulin, significantly more patients in the saxagliptin group were hospitalized for heart failure [47]. The dose of DPP-4 inhibitors (with the exception of linagliptin) should be adjusted in patients with renal insufficiency. (See "Dipeptidyl peptidase 4 (DPP-4) inhibitors for 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 'Adverse effects'.)

Insulin can also be considered a first-line therapy for all patients with type 2 diabetes, particularly patients presenting with symptomatic or poorly controlled diabetes (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) or in patients in whom it is difficult to distinguish type 1 from type 2 diabetes. (See "Insulin therapy in type 2 diabetes mellitus".)

PERSISTENT HYPERGLYCEMIA — After a successful initial response to oral therapy, many patients fail to maintain target glycated hemoglobin (A1C) levels. If glycemic goals are not met with a single agent, the older patient should be evaluated for contributing causes, such as difficulty adhering to the medication, side effects, or poor understanding of the nutrition plan [2,8]. 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.

For patients who fail initial therapy, there are a number of agents that are available and can be used with metformin or a sulfonylurea (table 1). The options are similar in older and in younger patients. The selection of drugs is based upon clinical trial evidence and clinical experience in achieving glycemic targets, with the recognition that there is a paucity of high-quality head-to-head drug comparison trials, particularly trials with clinically important health outcomes (cardiovascular events, mortality). There are few data specifically addressing drug therapy in older patients [8,10,38]. However, most diabetes drug trials included a wide range of patients, including those >65 years of age. These trials are reviewed separately. (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 'Treatment options'.)

Single agent failure — The therapeutic options for patients with persistent hyperglycemia (above individualized target) who are taking metformin or a sulfonylurea include adding a second oral or injectable agent, including insulin, or switching to insulin.

For older patients who have persistent hyperglycemia with lifestyle intervention and metformin, we suggest adding a short-acting sulfonylurea such as glipizide (algorithm 1). Alternative options include adding basal insulin (preferred in those with A1C >9 percent [74.9 mmol/mol] or with persistent symptomatic hyperglycemia), repaglinide, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide 1 (GLP-1) receptor agonist. 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.

For older patients who have persistent hyperglycemia (A1C >8.5 percent) with lifestyle intervention and sulfonylurea (contraindications to metformin), we suggest switching to basal insulin.

Insulin should be carefully titrated to avoid hypoglycemia and related complications. (See 'Avoiding hypoglycemia' above.)

For such patients with A1C above glycemic targets but ≤8.5 percent, there are a number of agents that are available and can be used with a sulfonylurea (as an alternative to switching to basal insulin). Options include DPP-4 inhibitors, GLP-1 agonists, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and alpha glucosidase inhibitors. All of these medications have advantages and disadvantages (table 1).

The choice of therapy should be individualized based upon patient characteristics, preferences, and costs. These agents are discussed in detail in the individual topic reviews. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of diabetes mellitus" and "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus" and "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus" and "Alpha-glucosidase inhibitors and lipase inhibitors for treatment of diabetes mellitus".)

Dual agent failure — For patients who do not achieve A1C goals with two agents (eg, metformin and sulfonylurea), we suggest starting or intensifying insulin therapy. 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. 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' 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'.)

Insulin initiation — Insulin is sometimes underutilized in older adults because of fear (by the clinician, patient, or family) that it is too complicated or dangerous. With the availability of long-acting insulins, it has become easier to use once-daily long-acting insulin as monotherapy or add once-daily insulin to oral hypoglycemic medications in older patients who have suboptimal glycemic control. Patients may wrongly assume that their symptoms of fatigue are due to “old age” rather than hyperglycemia. However, in many older patients, quality of life improves substantially when they take one or two daily doses of intermediate or long-acting insulin. (See "General principles of insulin therapy in diabetes mellitus".)

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.

Insulin should be carefully titrated to avoid hypoglycemia and related complications. (See 'Avoiding hypoglycemia' above and "Management of hypoglycemia during treatment of diabetes mellitus", section on 'Strategies to prevent hypoglycemia'.)

We typically start with bedtime intermediate-acting insulin or bedtime or morning long-acting insulin (10 units or 0.2 units per kg). The dose can be adjusted once weekly to reach the target fasting blood sugar. Insulin metabolism is altered in patients with chronic renal failure, so that less insulin is needed when the glomerular filtration rate (GFR) is below 50 mL/min. (See "Management of hyperglycemia in patients with type 2 diabetes and pre-dialysis chronic kidney disease or end-stage renal 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".)

MONITORING OF GLYCEMIA — Monitoring is usually necessary to achieve glycemic goals. We typically monitor glycated hemoglobin (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 glycemic goals. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Glycated hemoglobin'.)

Blood glucose concentrations can also be monitored at home by the patient or a caregiver. Self-monitoring of blood glucose (SMBG) can be considered in select older patients, depending upon medications and functional a nd cognitive abilities [2,8]. SMBG may be helpful in older patients with type 2 diabetes who take medications that can cause hypoglycemia (eg, insulin). 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, SMBG may not be necessary at all, or only in unusual circumstances, 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 "Blood glucose self-monitoring in management of adults with diabetes mellitus", section on 'Type 2 diabetes'.)

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 2). In particular, complications that impair functional capacity (eg, retinopathy, foot problems) should be identified and treated promptly [10].

Retinopathy — The prevalence of retinopathy increases progressively with increasing duration of diabetes (figure 1). (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 more common in older diabetic compared with nondiabetic subjects. Cataracts are over twice as common in people over age 65 years with diabetes compared with similarly-aged nondiabetic subjects (38.4 percent versus 16.6 percent), while glaucoma is almost three times more common (11.2 percent versus 3.8 percent) [48].

Nephropathy — The availability of effective therapy for diabetic nephropathy with angiotensin-converting enzyme (ACE) inhibitors 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 ACE receptor blocker, 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 [49,50]. (See "Treatment 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 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 and mortality compared with older individuals without diabetes [20]. In addition, they are at high risk for polypharmacy, functional disabilities, and common geriatric syndromes that include cognitive impairment, depression, urinary incontinence, falls, and persistent pain [2].

Cognitive impairment — Diabetes is associated with increased risk of dementia (see "Risk factors for cognitive decline and dementia", section on 'Diabetes mellitus'). Many older patients with dementia remain undiagnosed, particularly in the early stages. Older patients with diabetes and cognitive dysfunction may have difficulty performing self-management and following complicated treatment regimens. Cognitive function should be assessed in older diabetic patients when there is:

Nonadherence with therapy

Frequent episodes of hypoglycemia

Deterioration of glycemic control without obvious explanation (see "Evaluation of cognitive impairment and dementia")

Depression — Depression occurs at a higher rate in older patients with diabetes compared with age-matched controls [51,52]. Depression is frequently undiagnosed and remains untreated in this high-risk population [53].

Depression has been associated with poor glycemic control and with accelerated rates of coronary heart disease (CHD) in diabetic patients [54]. Early identification with a short screening tool (such as a geriatric depression scale) and treatment may help achieve better glycemic control [55].

Polypharmacy — 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 the patient's ability to manage their diabetes. Therefore, the medication list should be kept current and reviewed at each visit [2,8].

Falls — The increased risk of falls in older adults with diabetes is multifactorial. Presence of peripheral and/or autonomic neuropathy, reduced renal function, muscle weakness, functional disability, loss of vision, polypharmacy, comorbidities like osteoarthritis, and even mild hypoglycemia may contribute to falls in frail older adults. (See "Falls in older persons: Risk factors and patient evaluation".)

While good glycemic control prevents progression of some diabetes complications and therefore may decrease the risk of falls, hypoglycemia that occurs as a result of intensive glycemic control may increase the risk of falls. In a prospective observational study of 446 older adults with diabetes (mean age 74 years), intensive glycemic control (glycated hemoglobin [A1C] ≤6 versus >8 percent) was associated with an increased risk of falls in insulin users (odds ratio [OR] 4.4, 95% CI 1.3-14.5) but not in those treated with oral agents (OR 1.3, 95% CI 0.7-2.5) [56]. Potential reasons for the discrepancy include a greater duration or severity of diabetes or a greater number of hypoglycemic episodes in patients treated with insulin versus oral agents, possibilities which were not rigorously explored in this observational study.

Nevertheless, the benefits of improved glycemic control to reduce diabetes-related complications (and decrease risk of falls) must be balanced with the possible increased risk of falls with intensive insulin therapy. These findings support the use of less rigorous glycemic goals in older adults (see 'Glycemic targets' above). In addition, identifying the causes of falls and initiating exercise programs may reduce the risk of falls in these individuals.

Urinary incontinence — Diabetes increases a woman's risk of developing urinary incontinence. Risk factors include urinary tract infection, vaginal infection, autonomic neuropathy (resulting in either neurogenic bladder or fecal impaction) and polyuria due to hyperglycemia. Although there is no direct evidence to suggest deleterious effect of incontinence on diabetes control, identification and treatment are recommended to improve quality of life in women. (See "Treatment of urinary incontinence in women".)

Nursing home patients — There are few studies and guidelines directed at care of older adults with diabetes residing in nursing homes. Life expectancy, quality of life, severe functional disabilities and other co-existing conditions mentioned above affect goal setting and management plans. Exercise as tolerated in any form continues to be important for all patients. Regular diet without concentrated sweets may improve quality of life and prevent weight loss.

Treatment regimens should be chosen to achieve maximal glycemic control possible, with a focus on avoidance of hypoglycemia and control of hyperglycemic symptoms.

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. 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. Thus, management of diabetes in older adults should be individualized, taking into account these variables. (See 'Treatment goals' above.)

Goals for glycemic control, as well as risk factor management, should be individualized based upon the individual's overall health, risk for hypoglycemia, and projected period of survival, since the risk of complications is duration-dependent. (See 'Glycemic targets' 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 "Management of hypoglycemia during treatment of diabetes mellitus", section on 'Strategies to prevent hypoglycemia'.)

As in younger patients with diabetes, cardiovascular risk reduction should be focused upon smoking cessation, treatment of hypertension and dyslipidemia, exercise, and aspirin therapy when indicated. (See 'Cardiovascular risk reduction' above.)

Older patients with diabetes should receive individualized counseling regarding lifestyle modification, including a medical nutrition evaluation. The nutrition prescription is tailored for older people with diabetes based upon medical, lifestyle, and personal factors. (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 all 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. (See 'Drug therapy' above and 'Metformin' 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.

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. (See 'Drug therapy' above and 'Metformin' above.)

For patients with contraindications and/or intolerance to metformin, we suggest a short-acting sulfonylurea (eg, glipizide) (Grade 2B). Other options include repaglinide, dipeptidyl peptidase 4 (DPP-4) inhibitors, or insulin. (See 'Contraindications to metformin' above.)

For patients who are intolerant of or are not candidates for metformin or sulfonylureas, repaglinide is a reasonable alternative, particularly in a patient with chronic kidney disease at risk for hypoglycemia.

DPP-4 inhibitors can also be considered as monotherapy in older patients who are intolerant of or have contraindications to metformin, sulfonylureas, or repaglinide. Since they are relatively weak agents and usually lower A1C levels by only 0.6 percent, DPP-4 inhibitors should only be used as monotherapy when the A1C level is relatively close to the goal level. DPP-4 inhibitors have no risk of hypoglycemia and are weight neutral when used as monotherapy. However, the long-term safety with this class of drug has not been established, and they are relatively expensive.

If glycemic goals are not met with a single agent, the older patient should be evaluated for contributing causes, such as difficulty adhering to the medication, side effects, or poor understanding of the nutrition plan. If glycemic control is still above target, an additional agent is needed. The therapeutic options (table 1) for patients who fail initial therapy with lifestyle intervention and metformin or a sulfonylurea are similar in older and in younger patients. (See 'Persistent hyperglycemia' above.)

For older patients who have persistent hyperglycemia above their individualized glycemic target despite treatment with lifestyle intervention and metformin, we suggest adding a short-acting sulfonylurea such as glipizide (Grade 2B) (algorithm 1). Alternative options include adding basal insulin (preferred in those with A1C >9 percent [74.9 mmol/mol] or with persistent symptomatic hyperglycemia), repaglinide, a DPP-4 inhibitor, or a glucagon-like peptide 1 (GLP-1) receptor agonist. (See 'Persistent hyperglycemia' above.)

For older patients who have persistent hyperglycemia (A1C >8.5 percent) with lifestyle intervention and sulfonylurea (contraindications to metformin), we suggest switching to basal insulin (Grade 2B). For such patients with A1C above glycemic targets but ≤8.5 percent, there are a number of agents that are available and can be used with a sulfonylurea (as an alternative to switching to basal insulin). Options include DPP-4 inhibitors, GLP-1 agonists, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and alpha glucosidase inhibitors. All of these medications have advantages and disadvantages (table 1). The choice of therapy should be individualized based upon patient characteristics, preferences, and costs. (See 'Persistent hyperglycemia' above and "Management of persistent hyperglycemia in type 2 diabetes mellitus".)

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 2). In particular, complications that impair functional capacity (eg, retinopathy, foot problems) should be identified and treated promptly. (See 'Screening for microvascular complications' above.)

Older adults with diabetes are at high risk for polypharmacy, functional disabilities, and common geriatric syndromes that include cognitive impairment, depression, urinary incontinence, falls, and persistent pain. (See 'Common geriatric syndromes associated with diabetes' above.)

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