Contents Treatment of Type 2 Diabetes M

Treatment of type 2 diabetes mellitus in the older patient
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Official reprint from UpToDate

www.uptodate.com 2014 UpToDate
Authors
David K McCulloch, MD
Medha Munshi, MD
Section Editors
David M Nathan, MD
Kenneth E Schmader, MD
Deputy Editor
Jean E Mulder, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2014. | This topic last updated: May 02, 2014.
INTRODUCTION The prevalence of type 2 diabetes continues to increase steadily as more people live
longer and grow heavier. In the 2005-2006 National Health and Nutrition Examination Survey (NHANES)
of community dwelling adults, the prevalence of diabetes increased with age and peaked at age 60 to 74
years (crude prevalence 17.6 percent) [1]. From 1995 to 2004, the overall prevalence of type 2 diabetes in
nursing home residents increased from 16 to 23 percent [2].
Older adults with diabetes are at risk of developing a similar spectrum of macrovascular and
microvascular complications as their younger counterparts with diabetes. However, their absolute risk for
cardiovascular disease is much higher than younger adults. Older adults with diabetes suffer excess
morbidity and mortality compared with older individuals without diabetes [3]. 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 [4].
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".)
INDIVIDUALIZING MANAGEMENT Older adults with diabetes are a heterogeneous population that
includes persons residing independently in communities, in assisted care facilities, or in nursing homes.
Thus older adults with diabetes can be fit and healthy or frail with many comorbidities and functional
disabilities.
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. However, 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 [5]. 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 older patients.
Hyperglycemia increases dehydration and impairs vision and cognition [6], 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. Goals for glycemic
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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 similar to those developed for younger adults (<7.0 percent). The results of the
Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial suggest that a target A1C of 7.0 to 7.9
percent (achieving a median of 7.5 percent) may be safer than a lower target for patients with longstanding type 2 diabetes who are at high risk for cardiovascular disease [7]. Thus, the goal should be
somewhat higher (8.0 percent) in 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 and
should include efforts to preserve quality of life and avoid hypoglycemia and related complications. 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
[4,8-12]. (See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on
'Glycemic targets'.)
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 risk of hypoglycemia, which may lead to impaired cognition and function,
is substantially increased in older adults. In addition, older adults may have more neuroglycopenic
manifestations of hypoglycemia (dizziness, weakness, delirium, confusion) compared with adrenergic
manifestations (tremors, sweating). These symptoms may be missed or misconstrued as primary
neurological 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 [13]. 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 [14].
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].
Lifestyle modification Diet, weight reduction, and exercise can all 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 'Nonpharmacologic 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
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improvements in fasting plasma glucose (-18.9 versus -1.4 mg/dL) and A1C (-0.5 percentage points
versus no change) than control patients [16].
In addition, 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, compared with the younger age groups [17,18]. These data suggest that older persons
can respond well to lifestyle programs. Thus, all older patients with diabetes should receive a medical
nutrition evaluation. (See "Prevention of type 2 diabetes mellitus", section on 'Lifestyle modification' and
"Nutritional considerations in type 2 diabetes mellitus".)
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 [4,19].
Older adults are as much at risk for under-nutrition as for obesity. Weight loss increases the risk of
morbidity and mortality in older adults [20]. Thus, an involuntary loss of weight should be addressed
in the medical nutrition evaluation.
Drug therapy There are few data specifically addressing drug therapy in older patients [21]. 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. 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.
The following recommendations are based upon trials carried out in the general population and from
clinical experience. They are consistent with the AGS, the ADA, the IDF, and the European Diabetes
Working Party guidelines [4,8-12].
For older patients who do not have contraindications to metformin (eg, renal impairment or severe heart
failure), we prefer to initiate therapy with metformin (see "Metformin in the treatment of adults with type 2
diabetes mellitus", section on 'Lactic acidosis'). However in patients with contraindications and/or
intolerance to metformin, a short-acting sulfonylurea (eg, glipizide) is an alternative option. In a patient
with chronic kidney disease who is intolerant of sulfonylureas, repaglinide could be considered as initial
therapy. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus".)
After a successful initial response to oral therapy, many patients fail to maintain target 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 [4,11]. 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.
Indications for a second agent and therapeutic options for patients who fail initial therapy with lifestyle
intervention and metformin or a sulfonylurea are similar in older and in younger patients (table 1). This
topic is reviewed separately. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus".)
Metformin Metformin is an attractive agent to use in older adults due to a low risk of hypoglycemia.
However, it should be given with caution in older diabetic patients because of the risk of lactic acidosis.
Older patients often have impaired renal function despite an apparently normal serum creatinine
concentration. They are also at increased risk for developing other conditions that reduce renal function
further or cause lactic acidosis (eg, myocardial infarction [MI], stroke, cardiac failure, pneumonia). A
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calculated (or estimated) GFR >30 mL/min has been suggested as a safe level of kidney function for the
use of metformin.
Weight loss and gastrointestinal side effects may also be limiting factors in older adults taking metformin.
Therefore, metformin should be used with caution in older patients. Contraindications to its use are
reviewed elsewhere. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on
'Lactic acidosis'.)
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.
Sulfonylurea drugs 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). Thus, we avoid the use of long-acting sulfonylureas in older adults. We prefer
to use a short-acting sulfonylurea, such as glipizide. (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 one
observational study, the frequency in patients over age 65 treated with either glyburide or chlorpropamide
was similar (16.6 episodes per 1000 person-years) [22]. In contrast, 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 [23].
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 [24]
After being in the hospital [22]
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.
Thiazolidinediones The thiazolidinediones (rosiglitazone and pioglitazone) improve insulin
resistance. They also may increase insulin secretion in response to glucose, at least in patients with
impaired glucose tolerance [25].
The thiazolidinediones may be considered for some older patients, particularly those with lower initial A1C
values, if there are specific contraindications to sulfonylureas or if they are not able or willing to consider
insulin. They can be given to patients who have impaired renal function, are well tolerated in older adults,
and do not cause hypoglycemia. However, thiazolidinediones should not be used in patients with class III
or IV heart failure. In addition, limited experience, high cost, and concerns regarding fluid retention,
congestive heart failure, MI, and fractures limit their usefulness, particularly in older adults. If a
thiazolidinedione is to be used as therapy, pioglitazone is preferred because of the greater concern about
atherogenic lipid profiles and a potential increased risk for cardiovascular events with rosiglitazone. In
2010, the European Medicines Agency suspended sales of rosiglitazone. In the United States,
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rosiglitazone is only available through a Risk Evaluation and Mitigation Strategy program. New concerns
regarding increased risk for bladder cancer with pioglitazone, in addition to fluid retention and bone loss,
have led to decreased enthusiasm for its use. (See "Thiazolidinediones in the treatment of diabetes
mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of diabetes
mellitus", section on 'Safety' and "Heart failure in diabetes mellitus".)
Meglitinides 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. 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 [26]. Unlike nateglinide, repaglinide is principally metabolized by the liver, with less than 10
percent renally excreted. Dose adjustments with this agent 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".)
Alpha-glucosidase inhibitors Acarbose and miglitol inhibit the gastrointestinal alpha-glucosidases
that convert dietary starch and other complex carbohydrates into monosaccharides, thereby slowing the
absorption of glucose, which results in a slower rise in postprandial blood glucose concentrations. These
drugs may be used alone, or in combination with insulin, a sulfonylurea, and metformin.
Acarbose and miglitol have not been widely tested in older diabetic patients, but are likely to be fairly safe
and effective. The main side effects that limit their use are flatulence and diarrhea, which are very
common. (See "Alpha-glucosidase inhibitors and lipase inhibitors for treatment of diabetes mellitus".)
DPP-IV inhibitors Dipeptidyl peptidase IV (DPP-IV) is a ubiquitous enzyme that deactivates a
variety of other bioactive peptides, including glucagon-like peptide-1 (GLP-1) and glucose dependent
insulinotropic polypeptide (GIP); therefore, its inhibition could potentially affect glucose regulation through
multiple effects. DPP-IV inhibitors have been shown to be moderately effective as monotherapy or when
used in combination with metformin, sulfonylureas, or thiazolidinediones. They are relatively weak agents
and usually lower A1C levels by only 0.6 percent.
DPP-IV inhibitors have no risk of hypoglycemia and are weight-neutral, when used as monotherapy, and
therefore may be attractive agents to use in older adults. However, the long-term safety with this class of
drug has not been established, and they are relatively expensive. The dose of DPP-IV inhibitors should be
adjusted in patients with renal insufficiency.
GLP-1 therapies The role of gastrointestinal peptides in glucose homeostasis is illustrated by the
incretin effect, in which oral glucose has a greater stimulatory effect on insulin secretion than intravenous
glucose. This effect is mediated by several gastrointestinal peptides, particularly GLP-1. Exenatide,
liraglutide, and albiglutide are GLP-1 receptor agonists available for use as monotherapy as an adjunct to
diet and exercise or in combination with oral agents in adults with type 2 diabetes. Exenatide is
administered twice daily or once weekly with a long-acting release formulation, liraglutide once daily, and
albiglutide once weekly by subcutaneous injection. (See "Glucagon-like peptide-1-based therapies for the
treatment of type 2 diabetes mellitus".)
There is no risk of hypoglycemia with the use of GLP-1 agonists alone. They are sometimes associated
with significant reduction in weight. The most common adverse events are nausea, vomiting, and
diarrhea, occurring in 10 to 40 percent of treated patients. There have been postmarketing reports of
acute pancreatitis and deterioration in renal function in patients taking GLP-1 therapies. However, there
are insufficient data to know if there is a causal relationship. Due to concerns about renal toxicity,
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exenatide should not be used in patients with a creatinine clearance below 30 mL/min. (See "Glucagonlike peptide-1-based therapies for the treatment of type 2 diabetes mellitus".)
Pramlintide Pramlintide is a synthetic analog of amylin that is administered by mealtime
subcutaneous injection with insulin. It is available for the treatment of both type 1 and insulin-treated type
2 diabetes. It requires multiple subcutaneous injections and, therefore, its role in the management of
diabetes in older adults is limited. (See "Amylin analogs for the treatment of diabetes mellitus", section on
'Pramlintide'.)
Insulin 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 intermediateor 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 metabolism is altered in patients with chronic renal failure, so that less insulin is needed when the
GFR is below 50 mL/min.
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 blood glucose Monitoring is usually necessary to achieve glycemic goals. 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 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. The
effectiveness of self-monitoring of blood glucose (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'.)
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, self-monitoring of glucose 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.
Thus, SMBG can be considered in select older patients, depending upon medications and functional and
cognitive abilities [4,11].
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SCREENING FOR MICROVASCULAR COMPLICATIONS 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).
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) [27].
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 [28,29]. (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".)
CARDIOVASCULAR RISK REDUCTION 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, and that the effect of most interventions is more pronounced in them.
Risk reduction should be focused upon the following areas:
Smoking cessation
Treatment of hypertension
Treatment of dyslipidemia
Aspirin therapy
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Exercise
Smoking cessation Smoking in patients with diabetes mellitus is an independent risk factor for allcause mortality, due largely to cardiovascular disease. Therefore, smoking cessation should be vigorously
promoted. (See "Smoking and cardiovascular risk in diabetes mellitus".)
Treatment of hypertension Treatment of hypertension in older patients is clearly beneficial, including
patients over age 80. 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 Several abnormalities in lipid metabolism may contribute to the increase in
atherosclerosis associated with diabetes. The beneficial effects of lipid lowering therapy may be evident in
as early as six months [30]. In addition, the relative reduction of cardiovascular disease with serum lowdensity lipoprotein (LDL) reduction is similar in older and younger patients with diabetes [31,32]. (See
"Prevalence of and risk factors for coronary heart disease in diabetes mellitus".)
We recommend use of a statin drug (unless contraindicated) to lower cholesterol in all older diabetics with
a persistent LDL cholesterol value above 100 mg/dL (2.6 mmol/L), with a goal of reducing LDL below 100
mg/dL (2.6 mmol/L). In patients with diabetes who already have cardiovascular disease, a goal LDL of 70
to 80 mg/dL (1.8 to 2.1 mmol/L) is warranted, particularly in very high-risk patients. We also recommend
drug therapy in those with a serum high-density lipoprotein (HDL) cholesterol concentration below 35
mg/dL (0.9 mmol/L) or marked hypertriglyceridemia (400 mg/dL [4.5 mmol/L]). More detailed information
on the use of lipid-lowering drugs for secondary prevention of CHD is found elsewhere. (See "Intensity of
lipid lowering therapy in secondary prevention of cardiovascular disease" and "Clinical trials of cholesterol
lowering in patients with cardiovascular disease or diabetes", section on 'Heart Protection Study' and
"Clinical trials of cholesterol lowering in patients with cardiovascular disease or diabetes", section on
'ACCORD Lipid trial'.)
As with the goal for glycemic control, goals for risk factor management (hypertension, hyperlipidemia)
should be adjusted based upon older patients' life expectancy, comorbidities, cognitive status, and
personal preferences.
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
[33].
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 [34-37]. Studies of frail older people have shown that weight training should be
included in addition to aerobic exercises [38]. 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 "Effects of exercise in diabetes mellitus in adults".)
COMMON GERIATRIC SYNDROMES ASSOCIATED WITH DIABETES
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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 agematched controls [39,40]. Depression is frequently undiagnosed and remains untreated in this high risk
population [41].
Depression has been associated with poor glycemic control and with accelerated rates of coronary heart
disease (CHD) in diabetic patients [42]. Early identification with a short screening tool (such as a geriatric
depression scale) and treatment may help achieve better glycemic control [43].
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 his/her
diabetes. Therefore, the medication list should be kept current and reviewed at each visit [4,11].
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) [44]. 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 and prevention of urinary incontinence
in women".)
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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 appropriate target for glycated hemoglobin (A1C) in fit older patients who have a life expectancy
of over 10 years should be similar to those developed for younger adults (<7.0 percent). The goal
should be somewhat higher (8.0 percent) in frail older adults with multiple 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 and should include efforts to preserve quality of life and avoid
hypoglycemia and related complications. (See 'Glycemic targets' above.)
The risk of hypoglycemia, which may lead to impaired cognition and function, 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.)
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). In patients with contraindications and/or intolerance to metformin,
a short-acting sulfonylurea (eg, glipizide) is an alternative option. (See 'Drug therapy' above.)
In 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.
Dipeptidyl peptidase IV (DPP-IV)-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-IV inhibitors
should only be used as monotherapy when the A1C level is relatively close to the goal level. DPP-IV
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. (See 'Drug therapy' above.)
Indications for a second agent and therapeutic options for patients who fail initial therapy with
lifestyle intervention and metformin or a sulfonylurea are similar in older and in younger patients
(table 1). This topic is reviewed separately. (See "Management of persistent hyperglycemia in type 2
diabetes mellitus".)
Use of UpToDate is subject to the Subscription and License Agreement.
Page 11 of 17
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function: implications for rigorous glycemic control. Diabetes 2009; 58:360.
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with type 2 diabetes mellitus. JAMA 2009; 301:1565.
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hypoglycemia in normal aging in healthy men. Diabetes Care 1997; 20:135.
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among older adults with diabetes mellitus: results from a randomized controlled trial. Prev Med
2002; 34:252.
17. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with
lifestyle intervention or metformin. N Engl J Med 2002; 346:393.
18. Wing RR, Hamman RF, Bray GA, et al. Achieving weight and activity goals among diabetes
prevention program lifestyle participants. Obes Res 2004; 12:1426.
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interventions for diabetes: a position statement of the American Diabetes Association. Diabetes
Care 2008; 31 Suppl 1:S61.
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20. Wedick NM, Barrett-Connor E, Knoke JD, Wingard DL. The relationship between weight loss and
all-cause mortality in older men and women with and without diabetes mellitus: the Rancho
Bernardo study. J Am Geriatr Soc 2002; 50:1810.
21. Neumiller JJ, Setter SM. Pharmacologic management of the older patient with type 2 diabetes
mellitus. Am J Geriatr Pharmacother 2009; 7:324.
22. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and risk factors for serious hypoglycemia in
older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157:1681.
23. Burge MR, Schmitz-Fiorentino K, Fischette C, et al. A prospective trial of risk factors for
sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus. JAMA 1998; 279:137.
24. Bressler P, DeFronzo RA. Drugs and diabetes. Diabetes Rev 1994; 2:53.
25. Cavaghan MK, Ehrmann DA, Byrne MM, Polonsky KS. Treatment with the oral antidiabetic agent
troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance. J
Clin Invest 1997; 100:530.
26. Papa G, Fedele V, Rizzo MR, et al. Safety of type 2 diabetes treatment with repaglinide compared
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benefit of pravastatin in diabetics and enhanced role for HDL-cholesterol and triglycerides as risk
factors. Circulation 2002; 105:1424.
32. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol
lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
Lancet 2002; 360:7.
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myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.
Antiplatelet Trialists' Collaboration. BMJ 1994; 308:81.
34. Christmas C, Andersen RA. Exercise and older patients: guidelines for the clinician. J Am Geriatr
Soc 2000; 48:318.
35. Karani R, McLaughlin MA, Cassel CK. Exercise in the healthy older adult. Am J Geriatr Cardiol
2001; 10:269.
36. Morey MC, Pieper CF, Crowley GM, et al. Exercise adherence and 10-year mortality in chronically ill
older adults. J Am Geriatr Soc 2002; 50:1929.
37. Heath JM, Stuart MR. Prescribing exercise for frail elders. J Am Board Fam Pract 2002; 15:218.
38. Fiatarone MA, O'Neill EF, Ryan ND, et al. Exercise training and nutritional supplementation for
physical frailty in very elderly people. N Engl J Med 1994; 330:1769.
39. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in
adults with diabetes: a meta-analysis. Diabetes Care 2001; 24:1069.
40. Maraldi C, Volpato S, Penninx BW, et al. Diabetes mellitus, glycemic control, and incident
depressive symptoms among 70- to 79-year-old persons: the health, aging, and body composition
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42. Lustman PJ, Clouse RE. Treatment of depression in diabetes: impact on mood and medical
outcome. J Psychosom Res 2002; 53:917.
43. Lustman PJ, Freedland KE, Griffith LS, Clouse RE. Predicting response to cognitive behavior
therapy of depression in type 2 diabetes. Gen Hosp Psychiatry 1998; 20:302.
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and falls in older adults. Diabetes Care 2008; 31:391.
Topic 1776 Version 15.0
Page 14 of 17
GRAPHICS
Summary of glucose-lowering interventions
Expected
decrease in
Intervention
A1C with
Advantages
Disadvantages
monotherapy,
percent
Tier 1: Well-validated core
Step 1: Initial therapy
Lifestyle to
decrease
1.0 to 2.0
Broad benefits
Insufficient for most

within first year
1.0 to 2.0
Weight neutral
GI side effects,
weight and
increase
activity
Metformin
contraindicated with
renal insufficiency
Step 2: Additional therapy
Insulin
Sulfonylurea
1.5 to 3.5
1.0 to 2.0
No dose limit,
rapidly effective,
One to four injections

daily, monitoring,
improved lipid
profile
weight gain,
hypoglycemia,
analogues are
expensive
Rapidly effective
Weight gain,
hypoglycemia
(especially with
glibenclamide or
chlorpropamide)
Tier 2: Less well validated

TZDs
0.5 to 1.4
Improved lipid
Fluid retention, HF,
profile
(pioglitazone),
potential decrease
in MI
weight gain, bone

fractures, expensive,
potential increase in MI
(rosiglitazone)
(pioglitazone)
GLP-1 agonist
0.5 to 1.0
Weight loss
Requires injection,
frequent GI side
effects, long-term
safety not established,
expensive
Other therapy
Alpha-
0.5 to 0.8
Weight neutral
glucosidase
inhibitor
Glinide
Page 15 of 17
Frequent GI side
effects, three
times/day dosing,
expensive
0.5 to 1.5*
Rapidly effective
Weight gain, three

times/day dosing,
hypoglycemia,
expensive
Pramlintide
0.5 to 1.0
Weight loss
Three injections daily,

frequent GI side
effects, long-term
safety not established,
expensive
DPP-4 inhibitor
0.5 to 0.8
Weight neutral
Long-term safety not

established, expensive
A1C: glycated hemoglobin; TZD: thiazolidinedione; GLP-1: glucagon-like peptide-1; HF: heart
failure; GI: gastrointestinal; MI: myocardial infarction; DPP-4: dipeptidyl peptidase-4.
* Repaglinide more effective in lowering A1C than nateglinide.
Reproduced with permission from: Nathan DM, Buse JB, Davidson MB, et al. Medical Management
of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of
Therapy: A consensus statement of the American Diabetes Association and the European
Association for the Study of Diabetes. Diabetes Care 2009; 32:193-203. Copyright 2009
American Diabetes.
Graphic 56876 Version 5.0
Page 16 of 17
Monitoring in patients with diabetes mellitus

Intervention
Frequency
Notes
History and physical examination

Smoking cessation
counseling
Every visit
For smokers only.
Blood pressure
Every visit
Goal <140/80.
Dilated eye
examination
Annually*
Begin at onset of type 2 diabetes, three to five

years after onset of type 1 diabetes. Examine
more than annually if significant retinopathy.
Foot examination
Annually
Every visit if peripheral vascular disease or

neuropathy.
Dental
examination
Annually
Periodontal disease is more severe but not

necessarily more prevalent in patients with
diabetes.
Fasting serum lipid

profile
Annually
May obtain every two years if profile is low risk.
A1C
Every three to
six months
Goal <7 percent (may be lower or higher in

selected patients).
Urinary albuminto-creatinine ratio
Annually
Begin three to five years after onset of type 1

diabetes; protein excretion and serum creatinine
Laboratory studies
should also be monitored if persistent

albuminuria is present.
Serum creatinine
Initially, as
indicated
Vaccinations
Pneumococcus
One time
Patients over age 65 need a second dose if

vaccine was received 5 years previously and
age was <65 at time of vaccination.
Influenza
Annually
Hepatitis B
Three dose
Administer to unvaccinated adults who are ages
series
19 to 59 years. For older patients, administer

based upon risk of acquiring hepatitis B and
likelihood of an adequate immune response to
vaccination.
Education, self
management
review
Annually
* Less frequent screening (every two to three years) may be appropriate for some patients.
Page 17 of 17
Incidence of diabetic retinopathy increases over

time
Percent of diabetic patients with retinopathy according to duration of

disease in patients under the age of 30 years who were treated with
insulin (primarily type 1 diabetes) and patients over the age of 30 years
who were not treated with insulin (primarily type 2 diabetes).
Retinopathy increased over time in both groups, affecting virtually all
patients with type 1 diabetes by 20 years. The increased incidence in
type 2 diabetes at three years is a probable reflection of the difficulty in
determining the time of onset of that disease.
Data from: Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic
study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy
when age at diagnosis is 30 or more years. Arch Ophthalmol 1984; 102:527.
Disclosures
Disclosures: David K McCulloch, MD Nothing to disclose. Medha Munshi, MD Grant/Research/Clinical Trial Support: Sanofi
[Diabetes management (Glargine)]. David M Nathan, MD Nothing to disclose. Kenneth E Schmader, MD
Grant/Research/Clinical Trial Support: Merck [Herpes Zoster (Zoster vaccine)]. Jean E Mulder, MD Employee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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Treatment of type 2 diabetes mellitus in the older patient

Official reprint from UpToDate

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

SCREENING FOR MICROVASCULAR COMPLICATIONS Retinopathy, nephropathy, and foot

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Treatment of type 2 diabetes mellitus in the older patient

Insufficient for most

One to four injections

Tier 2: Less well validated

Fluid retention, HF,

weight gain, bone

Treatment of type 2 diabetes mellitus in the older patient

Weight gain, three

Three injections daily,

Long-term safety not

Treatment of type 2 diabetes mellitus in the older patient

Monitoring in patients with diabetes mellitus

History and physical examination

For smokers only.

Begin at onset of type 2 diabetes, three to five

Every visit if peripheral vascular disease or

Periodontal disease is more severe but not

Fasting serum lipid

May obtain every two years if profile is low risk.

Goal <7 percent (may be lower or higher in

Urinary albuminto-creatinine ratio

Begin three to five years after onset of type 1

should also be monitored if persistent

Patients over age 65 need a second dose if

Administer to unvaccinated adults who are ages

19 to 59 years. For older patients, administer

Treatment of type 2 diabetes mellitus in the older patient

Incidence of diabetic retinopathy increases over

Percent of diabetic patients with retinopathy according to duration of

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