Personalizing Treatment Plans for Older Patients With T2D

Felona Gunawan, MD


April 25, 2023

In the United States, type 2 diabetes (T2D) more commonly affects people older than 40 years, but it is most prevalent among adults over age 65, affecting more than 29% of this population. The heterogeneity in the health and functional status of older adults presents a challenge in the management and treatment of older patients with T2D. Moreover, there is an increased risk for health-related comorbidities and complications from diabetes treatment (eg, hypoglycemia) in older adults. Physiologic changes, such as decreased renal function, cognitive decline, and sarcopenia, may lead to an increased risk for adverse reactions to medications and require an individualized treatment approach. Although there have been a limited number of randomized controlled studies targeting older adults with multiple comorbidities and poor health status, subanalyses of diabetes trials with a subpopulation of older adults have provided additional evidence to better guide therapeutic approaches in caring for older patients with T2D.

Here's a guide to developing personalized therapeutic regimens for older patients with T2D using lifestyle interventions, pharmacotherapy, and diabetes technology.

Determining An Optimal Glycemic Target

An important first step in diabetes treatment is to determine the optimal glycemic target for patients. Although data support intensive glycemic control (A1c < 7%) to prevent complications from diabetes in younger patients with recently diagnosed disease, the data are less compelling in trials involving older populations with longer durations of T2D. One observational study with 71,092 older adults over age 60 reported a U-shaped correlation between A1c and mortality, with higher risks for mortality in those with A1c levels < 6% and ≥ 11% compared with those with A1c levels of 6%-9%. Risks for any diabetes complications were higher at an A1c level ≥ 8%. Another observational study reported a U-shaped association between A1c and mortality, with the lowest hazard ratio for mortality at an A1c level of about 7.5%. Similarly, the ACCORD trial, which included older and middle-age patients with T2D who had or were at risk for atherosclerotic cardiovascular disease, found that mortality followed a U-shaped curve at the low (A1c < 7%) and high (A1c > 8%) ends in patients who were given standard glycemic therapy. Hence, there has been a general trend to recommend less strict glycemic control in older adults.

However, it is important to remember that older patients with T2D are a heterogenous group. The spectrum includes adults with recent-onset diabetes with no or few complications, those with long-standing diabetes and many complications, and frail older adults with multiple comorbidities and complications. Determining the optimal glycemic target for an older patient with T2D requires assessment not only of the patient's medical status and comorbidities but also functional status, cognitive and psychological health, social situation, individual preferences, and life expectancy. The American Diabetes Association Standards of Medical Care in Diabetes provides the following guidance in determining the optimal glycemic control for older adults:

  • Healthy adults with few coexisting chronic illnesses and intact cognitive and functional status should have an A1c level < 7.0%-7.5%.

  • Adults with complex or intermediate comorbidities (multiple coexisting chronic illnesses, or two or more instrumental activities of daily living impairments, or mild to moderate cognitive impairment) should have an A1c level < 8.0%.

  • Patients with poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or two or more activities of daily living impairments) should avoid reliance on A1c, and the goal is to avoid hypoglycemia and symptomatic hyperglycemia.

Since older patients are at a higher risk for complications and adverse effects from polypharmacy, regular assessments are recommended and treatment plans should be routinely reviewed and modified to avoid overtreatment.

Lifestyle Interventions and Pharmacotherapy

Lifestyle interventions, such as exercise, optimal nutrition, and protein intake, are integral in treating older patients with T2D. Older adults should engage in regular exercise (ie, aerobic activity, weight-bearing exercise, or resistance training), and the activity should be customized to frailty status. Regular exercise improves insulin sensitivity and glucose control, enhances functional status, and provides cardiometabolic benefits. Optimal nutrition and adequate protein intake are also important to prevent the development or worsening of sarcopenia and frailty.

Several factors must be considered when choosing pharmacotherapy for T2D treatment in older adults. These patients are at higher risk for adverse reactions to medications that can trigger hypoglycemia and serious cardiovascular events, and worsen cognitive function. Therefore, side effects should always be reviewed when choosing antidiabetic drugs. The complexity of treatment plans needs to be matched with the patients' self-management abilities and available social support. Medication costs and insurance coverage should be considered because many older adults live on a fixed income. Although limited, data exist on the safety and efficacy of some glucose-lowering agents in older adults, which can provide guidance for choosing the optimal therapy for these patients.

Among the insulin sensitizers, metformin is most commonly used because of its efficacy, low risk for hypoglycemia, and affordability. Metformin can be safely used in the setting of reduced renal function down to the estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. However, metformin should be avoided in patients with more advanced renal disease, liver failure, or heart failure. In older patients with T2D, potential concerns of metformin include gastrointestinal side effects, leading to reduced appetite, mild weight loss, and risk for vitamin B12 deficiency.

Pioglitazone, an oral antidiabetic in the thiazolidinedione (TZD) class, also targets insulin resistance and may provide some cardiovascular benefits. However, these agents are not commonly used in treating older patients with T2D owing to associated risk for edema, heart failure, osteoporosis/fractures, and bladder cancer.

Sulfonylureas and meglitinide are insulin secretagogues, which can promote insulin release independent of glucose levels. Sulfonylureas are typically avoided in older patients because they are associated with high risk for hypoglycemia. Meglitinides have a lower hypoglycemia risk than sulfonylureas because of their short duration of action; however, they are more expensive and require multiple daily administration, which can lead to issues with adherence.

Since 2008, there have been numerous cardiovascular outcomes trials assessing the safety and efficacy of T2D therapies that included a subpopulation of older patients with either cardiovascular disease or at high risk for cardiovascular disease. Post hoc analysis of data from these trials and smaller studies dedicated to older adults demonstrated the safety and efficacy of most incretin-based therapies and sodium-glucose cotransporter 2 (SGLT2) inhibitors in these patients. These newer medications have low hypoglycemia risk if not used in combination with insulin or insulin secretagogues.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have the mildest side effect profile. However, they can be expensive and not reduce major adverse cardiovascular outcomes, and one agent, saxagliptin, has been associated with increased risk for heart failure hospitalization. Some glucagon-like peptide 1 (GLP-1) receptor agonists are effective in reducing major adverse cardiovascular events (cardiovascular deaths, stroke, and myocardial infarction) in patients older and younger than age 65. However, the gastrointestinal side effects and weight loss associated with this medication can be problematic for older patients. Most of the GLP-1 receptor agonists are injectables, which require good visual, motor, and cognitive skills for administration. SGLT2 inhibitors offer benefits for patients with T2D who have established cardiovascular disease, heart failure, and chronic kidney disease, with possible greater cardiovascular benefits in older adults. Adverse effects associated with SGLT2 inhibitors, such as weight loss, volume depletion, urinary incontinence, and genitourinary infections, may be a concern in older patients with T2D who are using these medications.

Because the insulin-secreting capacity of the pancreas declines with age, insulin therapy may be required for treatment of T2D in older patients. Insulin therapy can be complex and consideration must be given to patients' social circumstances, as well as their physical and cognitive abilities. Older adults may need adaptive strategies, such as additional lighting, magnification glass, and premixed syringes. Simplification of complex insulin therapy (discontinuation of prandial insulin or sliding scale, changing timing of basal insulin) and use of insulin analogs with lower hypoglycemia risks should be considered. Weight gain as a result of insulin therapy may be beneficial in older adults with sarcopenia or frailty.

T2D Technology for Glycemic Improvement

There have been major technological advancements in diabetes therapy. Continuous glucose monitors (CGMs) and automated insulin delivery systems can improve glycemic control, decrease the rate of hypoglycemia, and enhance the quality of life of older patients. Most of the studies evaluating the use of automated insulin delivery system in older patients have focused on those with type 1 diabetes and demonstrated improvement in glycemic control and/or reduced hypoglycemia. The DIAMOND trial demonstrated improved A1c and reduced glycemic variability with the use of CGM in adults older than 60 years with either type 1 or type 2 diabetes on multiple daily injections. Bluetooth-enabled "smart" insulin pens, which record the time and dose of insulin administrations, can also be a great asset in caring for older patients, especially those with cognitive impairment. With better insurance coverage, diabetes technologies may become more accessible and an asset in treating older patients with T2D.

In conclusion, management of T2D in older adults requires an individualized approach because of the heterogeneity in their health and functional status. Because cardiovascular disease is the leading cause of mortality in older patients with T2D, treatment plans should also address frequently coexisting cardiovascular risk factors, such as hypertension and hyperlipidemia. Clinicians should consider patients' overall health, comorbidities, cognitive and functional status, social support systems, preferences, and life expectancy when developing individualized therapeutic plans.

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