• Elisabetta Patorno, Phyo T Htoo, Robert J Glynn, Sebastian Schneeweiss, Deborah J Wexler, Ajinkya Pawar, Lily G Bessette, Kristyn Chin, Brendan M Everett, and Seoyoung C Kim.
• Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (E.P., P.T.H., R.J.G., S.S., A.P., L.G.B., K.C., B.M.E., S.C.K.).
• Ann. Intern. Med. 2021 Nov 1; 174 (11): 152815411528-1541.

BackgroundBoth sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD).ObjectiveTo evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD.DesignPopulation-based cohort study.SettingMedicare and 2 U.S. commercial claims data sets (April 2013 to December 2017).Participants1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy.MeasurementsPrimary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates.ResultsThe initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25]).LimitationTreatment selection was not randomized.ConclusionUse of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD.Primary Funding SourceDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.

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