Targets in Elderly Patients with Type 2 Diabetes

Research on glucose targets for the elderly finds intensive glucose-lowering techniques can have positive outcomes in patients >65 years.

Having hyperglycemia for a prolonged period can lead to cardiovascular diseases, amputations, blindness, renal problems, and nerve damage, among other complications. The relationship between these complications and elevated blood glucose led clinicians to make changes in therapy in the diabetic population. Therapeutic strategies have been developed throughout the years to lower glycated hemoglobin levels and decrease the risk of these complications. In the U.S., 25% of the diabetic population corresponds to our elderly population (>65 years). Older adults are at higher risk of developing more severe complications due to uncontrolled blood glucose. As the age increases, those >75 years are at more risk than those between 65 and 74. These severe complications lead to increased treatment costs that the elderly population cannot afford much of the time. Diabetic management is crucial in this population to maintain their health. Current guidelines consider overall health, comorbidities, hypoglycemic risk, cognitive status, and life expectancy to determine the best treatment. Challenges are present due to extensive variability within the population, specific patient factors, and an increased list of combination products. 

Recently, the use of intensive glucose lowering has been getting the interest of scientists and clinicians. Some studies evaluated the effect of this technique in the elderly population and the risk it has. The intensive glucose-lowering strategy targets an HbA1C <6.0%, but in the elderly population, this is considered too risky due to cardiovascular events and hypoglycemia events the medication and the condition may provoke. 

In previous trials, scientists looked at the effects of using intensive glucose lowering techniques and found a higher incidence of cardiovascular events and all-cause mortality in patients aged >65. In a recent randomized controlled trial, they studied the effects on vascular outcomes using intensive blood glucose lowering technique and blood pressure lowering in patients with type 2 diabetes compared to current guidelines’ recommendations. This study conducted in 215 centers around 20 countries included 11,140 individuals with type 2 diabetes at high risk of cardiovascular events. These individuals were randomized in the gliclazide or standard glucose-control based on guidelines and were followed up for five years. Another randomization included either individuals taking a fixed combination of perindopril 2mg and indapamide 0.625mg or a matching placebo after a 6-week run-in period. After randomization, participants were divided into two groups, including patients aged <65 and ≥65, and cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The primary outcome assessed in this study was the incidence of macrovascular and microvascular events. Also, they looked at all-cause death, cardiovascular death, new or worsening nephropathy and retinopathy, and severe hypoglycemia events. To analyze the data, they used t-tests, chi-square tests, cox regression models. They performed sensitivity analyses for patients 65-74 and ≥75 years. 

From the data obtained in this trial, 6613 participants were ≥65 years at baseline. They had longer disease duration, higher systolic and lower diastolic blood pressure, high cholesterol, HbA1C, and higher BMI than the younger group (p<0.001). In general, intensive glucose lowering technique was significantly associated with less risk of developing macrovascular and microvascular events (HR:0.90 95% CI: 0.82-0.98). When they looked at the two groups for the same effect, participants <65 years showed an H.R. of 0.86 (95% CI: 0.75-0.99), and for participants ≥65 years, the H.R. was 0.92 (95% CI: 0.83-1.03). Hypoglycemia events were higher in the group of participants <65 years using the intensive glucose-lowering technique (H.R.: 1.86 95%CI: 1.42-2.44; p<0.02). The effect of dementia and cognitive decline, assessed under cognitive function, was not significant between the groups (p=0.46). Also, they observed a higher incidence or worsening in retinopathy in the group using intensive blood glucose lowering technique (p=0.047).  

During this study, they showed that intensive glucose lowering reduced the risk of developing cardiovascular events independent of age. This study was also the first one that considered the cognitive status, which is vital because it affects the treatment goals. On the other hand, the study did not consider the outcomes in quality of life or treatment cost. Also, this study was a post hoc analysis of a trial, and the effects of using intensive glucose lowering were not the main objective of the study. Overall, results showed that using intensive glucose-lowering strategies can be beneficial for patients. 

Practice Pearls: 

• 25% of the elderly population in the U.S. has been diagnosed with type 2 diabetes mellitus, and adequate treatment can be challenging depending on the patient’s unique factors. 
• The benefits of using intensive glucose lowering techniques can be higher in elderly patients, including lower all-cause mortality and cardiovascular death risk. 
• Severe hypoglycemia can increase the risk of cardiovascular events and premature death, but the intensive glucose-lowering technique showed fewer episodes in patients >65 years. 

Ohkuma, T, et al. The Comparative Effects of Intensive Glucose Lowering in Diabetes Patients Aged Below or Above 65 Years: Results from the ADVANCE Trial. Diabetes Obes Metab (2021);  

Cushman, W. et al. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med (2008);  

Laura Martínez López, PharmD. Candidate 2021, Lake Erie College of Osteopathic Medicine, College of Pharmacy 

See more about glucose targets in the elderly and other populations.