Randomized trials demonstrate the cardioprotective effects of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). We evaluated their relative cardiovascular effectiveness in routine care populations with a broad spectrum of atherosclerotic cardiovascular diseases (CVDs) or heart failure (HF).
We identified Medicare beneficiaries from 2013 to 2017, aged >65 years, initiating SGLT2i (n=24 747) or GLP‐1RA (n=22 596) after a 1‐year baseline. On the basis of diagnoses during baseline, we classified patients into: (1) no HF or CVD, (2) HF but no CVD, (3) no HF but CVD, and (4) both HF and CVD. We identified hospitalized HF and atherosclerotic CVD outcomes from drug initiation until treatment changes, death, or disenrollment. We estimated propensity score–weighted 2‐year risk ratios (RRs) and risk differences, accounting for measured confounding, informative censoring, and competing risk. In patients with no CVD or HF, SGLT2i reduced the hospitalized HF risk compared with GLP‐1RA (propensity score–weighted RR, 0.65; 95% CI, 0.43–0.96). The association was strongest in those who had HF but no CVD (RR, 0.48; 95% CI, 0.25–0.85). The combined myocardial infarction, stroke, and mortality outcome risk was slightly higher for SGLT2i compared with GLP‐1RA in those without CVD or HF (RR, 1.31; 95% CI, 1.09–1.56). The association was favorable toward SGLT2i in subgroups with a history of HF.