Cardiovascular Outcomes Among Patients with Type 2 Diabetes Newly Initiated on Sodium-Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Other Antidiabetic Medications

BACKGROUND: Cardiovascular disease (CVD) remains the most prevalent cause of morbidity and mortality in patients with type 2 diabetes (T2D) and is a primary driver for health care costs associated with diabetes management. Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant reductions in cardiovascular endpoints in clinical trials compared with placebo. However, it is uncertain whether these findings can be applied to the broader T2D population because these trials specifically included high-risk patients with established CVD. OBJECTIVE: To evaluate and compare cardiovascular outcomes among adults with T2D newly initiated on SGLT-2is, GLP-1 RAs, and other antidiabetic medications (oADMs) in a real-world setting. METHODS: This retrospective new-user cohort study used administrative claims and electronic health record data from an integrated delivery network in Texas. Patients aged ≥18 years with T2D and ≥1 prescription claim for an SGLT-2i, a GLP-1 RA, or an oADM filled between April 2013 and December 2018 were included. Patients were divided into three 1:1 propensity-matched groups according to index medication identified. Primary outcomes were heart failure hospitalization and a composite end-point of myocardial infarction, stroke, unstable angina, or coronary revascularization. Cox proportional hazards regression was used to compare cumulative incidence of all outcome variables. RESULTS: Among 9,477 patients, 1,134 were initiated on SGLT-2is, 1,072 on GLP-1 RAs, and 7,271 on oADMs. Patients initiating SGLT-2is versus oADMs had significantly lower risk of the composite endpoint (HR = 0.64, 95% CI = 0.46-0.90), heart failure hospitalization (HR = 0.56, 95% CI = 0.39-0.81), and unstable angina requiring hospitalization (HR = 0.56, 95% CI = 0.39-0.81). Patients initiating GLP-1 RAs compared with oADMs had significantly lower risk of the composite endpoint (HR = 0.71, 95% CI = 0.52-0.98) and unstable angina requiring hospitalization (HR = 0.60, 95% CI = 0.41-0.86). No differences in cardiovascular outcomes were found between SGLT-2is and GLP-1 RAs. CONCLUSIONS: Both SGLT-2is and GLP-1 RAs 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, cardiovascular outcomes were similar between SGLT-2is and GLP-1 RAs.