Combined Glucagon-like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Use and Survival

The overall aim of this study was to evaluate the mortality effects of using glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in combination, versus in isolation, among United States Veterans with type 2 diabetes mellitus.

We performed an observational study evaluating mortality hazards with combined of GLP-1 RA and SGLT2i use among Veterans with type 2 diabetes mellitus. As of January 1, 2020, a total of 1 527 036 Veterans with an estimated glomerular filtration rate ≥ 15 mL/min/1.73 m² were identified for study inclusion. Prevalent use of GLP-1 RA and SGLT2i was defined by medication prescriptions beginning January 1, 2020. Follow up concluded December 31^st, 2023.

The medication phenotypes for GLP-1 RA/SGLT2i use were as follows: neither agent: 94.2%, GLP-1 RA alone: 2.5%, SGLT2i alone: 2.9%, and use of both: 0.4%. After a mean follow up of 3.6 years, 18.9% of the cohort died. The adjusted hazard ratios (AHRs, vs neither agent, all P < 0.001) with an intention-to-treat approach were: GLP-1 RA alone (AHR 0.89; [95%] CI 0.87-0.92), SGLT2i (AHR 0.85; CI 0.83-0.86), and both (AHR 0.64; CI 0.61-0.66); values with incident, as-treated approach were GLP-1 RA (HR 0.41; 95% CI 0.39-0.43), SGLT2i (AHR 0.56; CI 0.55-0.58), and both (HR 0.28; CI 0.26-0.31); and using a prevalent approach, GLP-1 RA (AHR 0.80; CI 0.78-0.82), SGLT2i (AHR 0.78; CI 0.76-0.80), and both (AHR 0.64; CI 0.60-0.70).

Combination therapy was associated with lower mortality than with either class in alone.