In patients with a history of heart failure but not cardiovascular disease (CVD), sodium-glucose cotransporter 2 inhibitors (SGLT2I) reduced cardiovascular risk vs glucagon-like peptide-1 receptor agonists (GLP-1RA) according to study findings published in the Journal of the American Heart Association.

In this large, population-based, observational cohort study, researchers sought to evaluate the relative effectiveness of SGLT2i vs GLP-1RA in routine care populations. The study population consisted of Medicare beneficiaries from 2013 to 2017. Patients were aged older than 65 years, and included 24,747 patients initiating SGLT2i and 22,596 patients initiating GLP-1RA after a 1-year baseline. Diagnoses during baseline allowed researchers to classify patients into 4 subgroups: Group 1 “No HF or CVD;” Group 2 “HF but no CVD;” Group 3No HF but CVD;” and Group 4 “both HF and CVD.” Statistical analysis estimated weighted 2-year risk ratios and risk differences.

Primary outcomes included hospitalization for heart failure (HF); the composite outcome of inpatient myocardial infarction, stroke, and all-cause mortality (major adverse cardiovascular events [MACEs]); and the composite outcome of MACE plus hospitalization for HF.

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For Group 1, SGLT2i instead of GLP-1RA more effectively reduced risk for hospitalization for HF (propensity score–weighted RR, 0.65; 95% CI, 0.43-0.96), though the combined stroke, myocardial infarction, and mortality outcome risk was slightly higher for SGLT2i (RR, 1.31; 95% CI, 1.09-1.56). The association was strongest in Group 2 (RR, 0.48; 95% CI, 0.25–0.85). The risk for hospitalization for HF was lower with SGLT2i for all subgroups.

Possible study limitations included the possibility that there could be residual or unmeasured confounding due to diabetes or CVD severity, and research models did not account for recurrent events.

“Further studies on the topic could shed lights on the potential cardioprotective mechanism of these antihyperglycemic agents as well as support the optimal prescribing practices in older, vulnerable patients with varying underlying cardiovascular comorbidities,” the researchers noted.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Htoo PT, Buse J, Cavender M, et al. 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. J Am Heart Assoc. Published online February 15, 2022. doi:10.1161/JAHA.121.022376