Evaluation of patient demographics, clinical characteristics, and cardiovascular outcomes in patients with type 2 diabetes newly initiated on sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and other antidiabetic medications

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Pineda, Elmor David

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Objectives: To evaluate and compare patient characteristics and cardiovascular outcomes among adults with type 2 diabetes (T2D) newly initiated on sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and other antidiabetic medications (oADMs). Methods: This retrospective new user cohort study used administrative claims and electronic health record data from an integrated delivery network in Texas. Patients ages ≥18 years with T2D and ≥1 prescription claim for either a SGLT-2i, GLP-1RA, or oADM filled between April 2013 through December 2018 were included. Patients were divided into three 1:1 propensity matched groups according to index medication identified. Pairwise comparisons of patient characteristics between SGLT-2is versus oADMs, GLP-1RAs versus oADMs, and SGLT-2is versus GLP-1RAs were compared before and after matching. Primary outcomes were heart failure hospitalization and a composite endpoint of myocardial infarction, stroke, unstable angina, or coronary. Secondary outcomes were the individual components of the composite endpoint. Cumulative incidences of all outcome variables were described using Kaplan-Meier failure plots and compared using log-rank tests and cox regression models. Results: Among 9,477 patients, 1,134 were SGL-2is initiators, 1,072 were GLP-1RA initiators, and 7,271 were oADM initiators. After propensity score matching, there were 815 matched pairs for SGLT-2i versus oADM), 817 pairs for GLP-RA versus oADM, and 947 pairs for SGLT-2i versus GLP-1RA. Patients initiating SGLT-2is versus oADMs had significantly lower risk of the composite endpoint (HR 0.69, 95% CI: 0.52-0.92), heart failure hospitalization (HR 0.66, 95% CI: 0.47-0.93), and unstable angina requiring hospitalization (HR 0.58, 95% CI: 0.41-0.82). Patients initiating SGLT-2is compared to oADMs had significantly lower risk of the composite endpoint (HR 0.70, 95% CI: 0.52- 0.94) and unstable angina requiring hospitalization (HR 0.59, 95% CI: 0.42-0.83). There were no differences in CV outcomes between SGLT-2is and GLP-1RAs. Conclusions: Both SGLT-2is and GLP-1RAs showed significant reductions in the composite outcome and unstable angina requiring hospitalization versus oADMs. However, only SGLT-2is were associated with a lower risk for heart failure hospitalizations. Nevertheless, CV outcomes were similar between SGLT-2is and GLP- 1RAs when compared to each other. This study provides real-world evidence for patients, payers, and providers, to consider selection of novel antidiabetic agents with CV benefits, SGLT-2is and GLP-1RAs, over other agents regardless of CVD status


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