Due to the high percentages of concurrent comorbidities, functional disability, frailty, cognitive impairment, and polypharmacy, diabetes management for the elderly is difficult. Thus, while selecting the best glucose-lowering medication for older patients with diabetes, the complexity of the treatment, side effects, and drug interactions are crucial factors to consider. Since 2012, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been marketed for decreasing blood sugar, meanwhile, numerous clinical trials have demonstrated their advantages beyond glucose-lowering such as reduced hospitalizations for heart failure, renal protection, and improvements in weight and blood pressure. SGLT2 inhibitors seem to be an appealing treatment alternative for older persons when treating numerous comorbidities is more common, given their various beneficial benefits, minimal added risk for hypoglycemia, and ease of administration. In clinical practice, however, there has been a significant reluctance to administer these drugs to elderly patients, especially very old persons (aged 75 years or more) due to a lack of long-term safety data.

The Dapagliflozin Effect on Cardiovascular Events (DECLARE)–TIMI 58 study was conducted to ascertain the CV and renal effects of dapagliflozin on a large patient population both with and without established cardiovascular disease, including a large cohort of elderly and very elderly patients. An additional investigation was conducted to examine the efficacy and safety of dapagliflozin stratified by age. More than 17, 000 patients were included, out of which, 9,253 patients were <65 years of age, 6,811 patients were aged between ≥65 to <75 years, and 1,096 patients were aged ≥75 years respectively.

In the study, major hypoglycemic events were less frequent with dapagliflozin in comparison to placebo. Besides, dapagliflozin also reduced the composite of cardiovascular death or hospitalization for heart failure consistently, with a hazard ratio (HR) of 0.88, 0.77, and 0.94 (0.65, 1.36) in the age-groups <65, ≥65 to <75, and ≥75 years, respectively. However, no significant decrease in the rates of major adverse cardiovascular events was observed in the age groups <65, ≥65 to <75, and ≥75 years, with HR reported as 0.93, 0.97, and 0.84 respectively. The relative risk reduction for the secondary prespecified cardiorenal composite outcome ranged from 18% to 28% in the different age groups with no heterogeneity. Safety outcomes, including fractures, volume depletion, cancer, urinary tract infections, and amputations were balanced with dapagliflozin, and acute kidney injury was also reduced in all age groups. Conditions like genital infections and diabetic ketoacidosis that can cause serious adverse effects or lead to discontinuation of the study drug were insignificant for dapagliflozin in comparison to the placebo. Hence, it can be concluded that the overall efficacy and safety of dapagliflozin were consistent regardless of age.

Reference: Cahn A et al., Diabetes Care. 2020 Feb;43(2):468-475.

Doi: 10.2337/dc19-1476.