Potential Unrealized Mortality Benefit of GLP‐1 Receptor Agonists and SGLT2 Inhibitors: A Report from the Veterans Health Administration Clinical Assessment, Reporting, and Tracking (CART) Program

AIMS Glucagon-like-peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransport-2 inhibitors (SGLT2i) reduced death and cardiovascular events in randomized trials, but uptake in clinical practice has lagged. We assessed the unrealized potential to reduce mortality with GLP-1RA or SGLT2i use in trial-eligible Veterans with type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). METHODS Veterans with T2D and CAD on angiography in 2014 who were untreated with GLP-1RA or SGLT2i were assessed for key eligibility criteria of the LEADER (GLP-1RA) and EMPA-REG OUTCOME (SGLT2i) trials. Trial hazard ratios and 95% confidence intervals for all-cause death were applied to deaths observed in Veterans through 2018 to estimate potential benefit of GLP-1RA or SGLT2i use. RESULTS Median observation was 4.3 years. Of 15,987 Veterans with T2D and CAD, 1182 (7.4%) were excluded for GLP-1RA or SGLT2i treatment. Of the remaining 13,415 patients, 4103 (30.1%) and 5313 (39.6%) fulfilled key criteria for the LEADER and EMPA-REG OUTCOME trials. Death occurred in 1009 (24.6%) of LEADER-eligible patients and 1335 (25.1%) of EMPA-REG OUTCOME-eligible patients. Under treatment with liraglutide in LEADER-eligible Veterans, a 3.5% (0.7-6.2%) potential mortality reduction, corresponding to 144 (28-253) fewer deaths (0.88 [0.17-1.56] per 100 person-years), might have been expected. Similarly, under treatment with empagliflozin in EMPA-REG OUTCOME-eligible Veterans, a 7.9% (4.5-10.8%) potential mortality reduction, corresponding to 418 (230-573) fewer deaths (1.98 [1.14-2.72] per 100 person-years) might have been expected. CONCLUSIONS This analysis indicates unrealized opportunities to reduce mortality in selected Veterans with T2D and CAD via increased use of GLP-1RA and SGLT2i. This article is protected by copyright. All rights reserved.