This retrospective cohort study compared the effectiveness of six antidiabetic medication (ADM) classes on major adverse cardiovascular events. Using nationwide U.S. administrative claims data from 2011-2015, we studied 132,737 insured adults with type 2 diabetes who started one of six ADM after taking metformin alone or no prior ADM. The key exposure was the new ADM class, which was filled ≥2 times. The composite primary outcome included hospitalization for one of the following conditions: heart failure, stroke, ischemic heart disease, and peripheral artery disease. Eligibility criteria and outcomes were ascertained using claims data. We used Cox regression to model the association between new ADM class and composite cardiovascular events, adjusting for baseline characteristics of patients, including prior use of metformin and cardiovascular medications, as well as prescribers and health plans. DPP-4 inhibitors (DPP-4) were the comparator given evidence of their cardiovascular neutrality. Overall, 5.5% of patients had a history of prior cardiovascular disease. There were 3,603 cardiovascular events during a mean follow-up of 1.3 years. Compared to DPP-4, the adjusted hazard ratios for each ADM class were: [sulfonylureas (SFU): HR 1.36, 95% CI: 1.23-1.49; basal insulin: HR 2.03, 1.81-2.27; thiazolidinediones (TZD): HR 0.89, 0.73-1.08; SGLT2 inhibitors (SGLT2): HR 0.80, 0.56-1.14; and GLP-1 receptor agonists (GLP-1): HR 0.78, 0.63-0.96]. The GLP-1 benefit was not robust across alternate modeling approaches. Among low-risk patients with type 2 diabetes, we found higher cardiovascular risk associated with SFU and basal insulin compared to newer ADM classes. Cardiovascular outcomes associated with DPP-4, GLP-1, and SGLT2 were similar in this population. Providers may consider prescribing these newer drugs routinely after metformin. Future clinical trials and data describing total costs of care will further inform providers’ choice of second-line ADM.


M. O'Brien: None. S.L. Karam: Research Support; Self; United Healthcare Services. A. Wallia: Research Support; Self; UnitedHealth Group. Consultant; Self; Glytec Systems, Lexicon Pharmaceuticals, Inc.. Research Support; Self; Eli Lilly and Company. R. Kang: Research Support; Self; UnitedHealth Group. A.J. Cooper: Research Support; Self; UnitedHealth Group. N. Lancki: Research Support; Self; United Healthcare Services. M.R. Moran: Research Support; Self; United Healthcare Services. D.T. Liss: Research Support; Self; United Healthcare Services. T.A. Prospect: Employee; Self; UnitedHealth Group. R.T. Ackermann: Consultant; Self; UnitedHealth Group.

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