Comparative Effectiveness and Safety of Sodium–Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults

Objective: Both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in RCTs of patients with type 2 diabetes (T2D) generally Methods: Using Medicare data (4/2013-12/2016), we identified 90,094 1:1 propensity score-matched T2D patients ≥66 years initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE, i.e., myocardial infarction, stroke or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections (GI), fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections (UTI), and overall mortality. We estimated hazard ratios (HR) and rate differences (RD) per 1000 person-years, controlling for 140 baseline covariates. Results: Compared with GLP-1RA, SGLT2i initiators had similar MACE risk [HR (95% CI)=0.98 (0.87-1.10); RD (95% CI)= -0.38 (-2.48,1.72)] and reduced HHF risk [HR=0.68 (0.57-0.80)]; RD= -3.23 (-4.68,-1.77)], over a median follow up of approximately 6 months. They also had 0.7 [RD=0.72 (0.02, 1.41)] more DKA, 0.9 [RD=0.90 (0.10, 1.70)] more LLA, 57.1 [RD=57.08 (53.45, 60.70)] more GI, and 7.1 [RD=-7.05 (-10.27, -3.83)] fewer AKI events. Conclusions: Among older adults, SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and GI, vs. GLP-1RA.