Cardiovascular Effectiveness of Sodium‐Glucose Cotransporter 2 Inhibitors and Glucagon‐Like Peptide‐1 Receptor Agonists in Older Patients in Routine Clinical Care With or Without History of Atherosclerotic Cardiovascular Diseases or Heart Failure

BACKGROUND: 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). METHODS AND RESULTS: 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. CONCLUSIONS: SGLT2i reduced the cardiovascular risk versus GLP‐1RA in patients with a history of HF but no CVD. Atherosclerotic CVD events were less frequent with GLP‐1RA in those without prior CVD or HF.