Sodium-glucose cotransporter 2 inhibitor, Glucagonlike peptide-1 receptor agonist, Type 2 diabetes, Atherosclerotic cardiovascular disease, Chronic kidney disease, Major adverse cardiovascular event, Diseases of the circulatory (Cardiovascular) system, RC666-701

Abstract Background Guidelines recommend combination therapy with glucagonlike peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) for cardiorenal risk reduction in people with type 2 diabetes (T2D); however, there is limited real-world evidence on the long-term effects of combination therapy on cardiometabolic and renal outcomes. The objective of this study was to assess cardiovascular (CV), metabolic, and renal effects of combination therapy with newer generation GLP-1RA (including once-weekly GLP-1RAs, once-daily oral semaglutide, and dual GLP-1/glucose-dependent insulinotropic polypeptide [GIP] agonists) and SGLT2i compared with SGLT2i alone. Methods This retrospective cohort study included data on US adults with T2D receiving SGLT2i from Komodo’s Healthcare Map from January 1, 2017, to June 30, 2023. The study included 100,455 people in the combination GLP-1RA and SGLT2i group and 339,540 people in the comparison SGLT2i group across 3 cohorts: T2D with atherosclerotic cardiovascular disease (ASCVD), T2D, and T2D with chronic kidney disease (CKD). Entropy balancing was used to balance patient characteristics. Time to first event of ischemic stroke, myocardial infarction (MI), 3-point major adverse cardiovascular event (MACE), and 5-point MACE in T2D with ASCVD cohort were measured. In the T2D cohort, follow-up and change in glycated hemoglobin (HbA1c) and weight, odds of achieving HbA1c