Safety of sodium-glucose cotransporter 2 inhibitors in elderly patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are particularly effective in preventing adverse outcomes of heart failure and chronic kidney disease, which are highly prevalent in the elderly. Here, we aimed to access the safety of SGLT2i in elderly patients with type 2 diabetes.

Materials And Methods: We performed a meta-analysis of randomized controlled trials (RCTs) reporting safety outcomes of the elderly (≥65 years) patients with type 2 diabetes, randomized to an SGLT2i or placebo. We recorded the incidence of acute kidney injury, volume depletion, genital tract infections, urinary tract infections, bone fractures, amputations, diabetic ketoacidosis, hypoglycaemia and drug discontinuation, by group of treatment.

Results: Of the 130 RCTs screened, only six reported data on elderly patients. In total, 19 986 patients were included. The SGLT2i discontinuation rate was approximately 20%. The risk of acute kidney injury was significantly lower among SGLT2i users compared with placebo [risk ratio (RR) 0.73; 95% CI 0.62-0.87]. SGLT2i were associated with a six-fold increased risk of genital tract infections (RR 6.55; 95% CI 2.09-20.5). The rate of amputations was increased only among canagliflozin users (RR 1.94, 95% CI 1.25-3). The risk of fractures, urinary tract infection, volume depletion, hypoglycaemia and diabetic ketoacidosis was similar between SGLT2i and placebo.

Conclusions: SGLT2is were well tolerated in the elderly. However, older patients are underrepresented in most RCTs and a call for action is need to favour clinical trials reporting safety outcomes stratified by age.