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Newer Glucose-Lowering Therapies in Older Adults with Type 2 Diabetes (2023)
Anika Bilal, MBBS, Richard E. Pratley, MD
INTRODUCTION
As life expectancy increases around the world, clinicians are increasingly faced with the formidable task of managing older adults with multiple diseases. Diabetes is common in the older adult population, affecting one in four people over 65 years of age.1 The global epidemic of diabetes, combined with increases in life expectancy, means that the population of older adults with diabetes will continue to grow in the foreseeable future. Indeed, by the year 2045, over 276 million older adults are projected to have diabetes.2 Older adults with diabetes have a shortened life expectancy, dying 4.6 years earlier on average, developing a disability 6 to 7 years earlier, and spending one to two more years in a disabled state than adults without diabetes.3
The advent of new glucose-lowering drugs in recent years, including dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose cotransporter 2 inhibitors (SGLT-2is), has provided clinicians with many more effective and safe treatment options to care for their older patients with diabetes. However, it is essential to know the advantages and disadvantages of these newer classes of glucose-lowering drugs in the aging population when incorporating them into an individualized treatment regimen. Certain SGLT-2i and GLP-1RAs have demonstrated benefits and are indicated to reduce the risk for cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD) progression in high-risk patients with diabetes, including older adults. Thus, the incorporation of these drugs into individualized treatment regimens to improve long-term outcomes should be considered for selected older individuals with type 2 diabetes (T2D) who are likely to benefit.
*Diabetes in Older Adults
-Heterogeneity of Diabetes in older adults
*Systemic Effects of Aging and Complications of Diabetes
Human aging is characterized by pathophysiological changes in virtually every organ system that can increase the risk of diabetes, impact the selection of therapies to control hyperglycemia, and increase the risk of complications and comorbidities. For example, a progressive loss of beta-cell insulin secretory capacity and the development of insulin resistance related to obesity and physical inactivity with aging are thought to contribute to the age-related increase in the incidence and prevalence of diabetes. People with diabetes are at an increased risk of developing microvascular and macrovascular complications, including diabetic retinopathy, neuropathy, nephropathy, coronary artery disease, HF, stroke, peripheral vascular disease, and lower-limb amputations that can be disabling and life-threatening.5 The risk of diabetic complications is increased with poor glycemic control and long-standing diabetes and is higher in older adults with diabetes. The presence of complications should be carefully assessed as this can impact goal setting as well as a selection of specific-glucose lowering medications.
-Cardiovascular aging and cardiovascular disease complications of diabetes
-Renal aging
-Hepatic aging
-Neurologic aging
*Hypoglycemia
Hypoglycemic episodes should be ascertained and addressed in all patients with diabetes during every visit, but this is especially important in older adults with diabetes. Assessment of hypoglycemia (eg, selected questions from the Diabetes Care Profile),36 hypoglycemic unawareness,37 assessment of skipped meals, repeated administration of medication, and stratification of future risk of hypoglycemia with validated risk calculators (eg, Kaiser Hypoglycemia Model)38 should be done routinely. Factors that increase the risk of treatment-associated hypoglycemia include the use of insulin/insulin secretagogues, impaired hepatic or renal function, frailty, longer diabetes duration, impaired cognition, hypoglycemic unawareness, history of severe hypoglycemic events, and polypharmacy.39 For older adults with T1D and older adults with T2D on multiple insulin injections, continuous glucose monitoring is recommended to reduce the risk of hypoglycemia.40,41
*TREATMENT GOALS
*EVIDENCE-BASED DIABETES MANAGEMENT WITH NEWER GLUCOSE-LOWERING THERAPIES
-Dipeptidyl Peptidase-4 Inhibitors
-Glucagon-Like Peptide-1 Receptor Agonists
-Sodium-Glucose Cotransporter 2 Inhibitors
*ASSESSMENT AND MANAGEMENT OF TYPE 2 DIABETES IN OLDER ADULTS
SUMMARY
Diabetes management is complicated in older adults and requires a multifaceted, personalized treatment plan. Assessment of multimorbidity, diabetic complications, geriatric syndromes, and cognition is essential for tailoring the diabetes regimen. In older patients with diabetes, less stringent glycemic targets may be considered depending on life expectancy, and functional and cognitive status. Limited research and guidelines are available for very old people (>75 years) with diabetes and for frail older adults, particularly those residing in long-term care facilities. Newer antihyperglycemic agents provide better safety and efficacy and less risk of hypoglycemia and in some cases are associated with cardiovascular and kidney benefits in older adults with T2D. As a result, guidelines have evolved to focus on the selection of treatments that can reduce the risk of CVD, HF, and CKD. As these comorbidities are common in older individuals with T2D, it is especially important to personalize therapy in this population.
Anika Bilal, MBBS, Richard E. Pratley, MD
INTRODUCTION
As life expectancy increases around the world, clinicians are increasingly faced with the formidable task of managing older adults with multiple diseases. Diabetes is common in the older adult population, affecting one in four people over 65 years of age.1 The global epidemic of diabetes, combined with increases in life expectancy, means that the population of older adults with diabetes will continue to grow in the foreseeable future. Indeed, by the year 2045, over 276 million older adults are projected to have diabetes.2 Older adults with diabetes have a shortened life expectancy, dying 4.6 years earlier on average, developing a disability 6 to 7 years earlier, and spending one to two more years in a disabled state than adults without diabetes.3
The advent of new glucose-lowering drugs in recent years, including dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose cotransporter 2 inhibitors (SGLT-2is), has provided clinicians with many more effective and safe treatment options to care for their older patients with diabetes. However, it is essential to know the advantages and disadvantages of these newer classes of glucose-lowering drugs in the aging population when incorporating them into an individualized treatment regimen. Certain SGLT-2i and GLP-1RAs have demonstrated benefits and are indicated to reduce the risk for cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD) progression in high-risk patients with diabetes, including older adults. Thus, the incorporation of these drugs into individualized treatment regimens to improve long-term outcomes should be considered for selected older individuals with type 2 diabetes (T2D) who are likely to benefit.
*Diabetes in Older Adults
-Heterogeneity of Diabetes in older adults
*Systemic Effects of Aging and Complications of Diabetes
Human aging is characterized by pathophysiological changes in virtually every organ system that can increase the risk of diabetes, impact the selection of therapies to control hyperglycemia, and increase the risk of complications and comorbidities. For example, a progressive loss of beta-cell insulin secretory capacity and the development of insulin resistance related to obesity and physical inactivity with aging are thought to contribute to the age-related increase in the incidence and prevalence of diabetes. People with diabetes are at an increased risk of developing microvascular and macrovascular complications, including diabetic retinopathy, neuropathy, nephropathy, coronary artery disease, HF, stroke, peripheral vascular disease, and lower-limb amputations that can be disabling and life-threatening.5 The risk of diabetic complications is increased with poor glycemic control and long-standing diabetes and is higher in older adults with diabetes. The presence of complications should be carefully assessed as this can impact goal setting as well as a selection of specific-glucose lowering medications.
-Cardiovascular aging and cardiovascular disease complications of diabetes
-Renal aging
-Hepatic aging
-Neurologic aging
*Hypoglycemia
Hypoglycemic episodes should be ascertained and addressed in all patients with diabetes during every visit, but this is especially important in older adults with diabetes. Assessment of hypoglycemia (eg, selected questions from the Diabetes Care Profile),36 hypoglycemic unawareness,37 assessment of skipped meals, repeated administration of medication, and stratification of future risk of hypoglycemia with validated risk calculators (eg, Kaiser Hypoglycemia Model)38 should be done routinely. Factors that increase the risk of treatment-associated hypoglycemia include the use of insulin/insulin secretagogues, impaired hepatic or renal function, frailty, longer diabetes duration, impaired cognition, hypoglycemic unawareness, history of severe hypoglycemic events, and polypharmacy.39 For older adults with T1D and older adults with T2D on multiple insulin injections, continuous glucose monitoring is recommended to reduce the risk of hypoglycemia.40,41
*TREATMENT GOALS
*EVIDENCE-BASED DIABETES MANAGEMENT WITH NEWER GLUCOSE-LOWERING THERAPIES
-Dipeptidyl Peptidase-4 Inhibitors
-Glucagon-Like Peptide-1 Receptor Agonists
-Sodium-Glucose Cotransporter 2 Inhibitors
*ASSESSMENT AND MANAGEMENT OF TYPE 2 DIABETES IN OLDER ADULTS
SUMMARY
Diabetes management is complicated in older adults and requires a multifaceted, personalized treatment plan. Assessment of multimorbidity, diabetic complications, geriatric syndromes, and cognition is essential for tailoring the diabetes regimen. In older patients with diabetes, less stringent glycemic targets may be considered depending on life expectancy, and functional and cognitive status. Limited research and guidelines are available for very old people (>75 years) with diabetes and for frail older adults, particularly those residing in long-term care facilities. Newer antihyperglycemic agents provide better safety and efficacy and less risk of hypoglycemia and in some cases are associated with cardiovascular and kidney benefits in older adults with T2D. As a result, guidelines have evolved to focus on the selection of treatments that can reduce the risk of CVD, HF, and CKD. As these comorbidities are common in older individuals with T2D, it is especially important to personalize therapy in this population.
