Both SGLT2i and GLP-1 RA have shown cardiovascular (CV) benefits in RCTs among diabetic patients generally younger than 65 years with CV disease. Whether these agents are associated with differential effectiveness and safety in routine care of older adults remains unexplored. Using claims data from Medicare (4/2013-12/2016), we identified 44,179 pairs of 1:1 propensity score-matched (PSM) patients ≥65 years with type 2 diabetes initiating a SGLT2i or a GLP-1 RA. We assessed a composite CV outcome (MI, stroke, or all-cause mortality), and hospitalization for heart failure (HHF). Safety outcomes of interest were severe hypoglycemia, bone fractures, lower-limb amputations (LLA), and diabetic ketoacidosis (DKA). We estimated HRs and 95% CIs in the PSM population well-balanced across >140 baseline covariates. Compared to GLP-1 RA, SGLT2i were associated with a similar risk of the composite CV outcome [HR (95% CI) = 1.04 (0.93-1.15)], and its components, but with decreased risk of HHF [0.68 (0.56-0.83)], over a mean 8.4-month follow-up (Table). Results were consistent in patients with and without CV disease. SGLT2i initiators had similar risk of severe hypoglycemia and fractures, but increased risk of LLA [1.47 (1.07-2.04)] and DKA [1.63 (1.16-2.28)]. Overall in 1,000 person-years, SGLT2i initiation vs. GLP-1 RA was associated with about 2.2 fewer HHF events, but 0.9 more LLA and 1.0 more DKA events.


E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim International GmbH. D.H. Kim: None. A. Pawar: None. S. Schneeweiss: Consultant; Self; Aetion, WHISCON, LLC. R.J. Glynn: Research Support; Self; AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Pfizer Inc. M. Munshi: Consultant; Self; Lilly Diabetes, Sanofi. L.G. Bessette: None. S.C. Kim: Research Support; Self; Bristol-Myers Squibb Company, Genentech, Inc., Pfizer Inc.

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