Association of GLP ‐1 Receptor Agonists Versus Other Antidiabetic Medications With Cardiovascular, Renal, and Liver Outcomes in Patients With Type 2 Diabetes

AIMS: To compare cardiovascular, kidney, and liver outcomes of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus seven other antidiabetic medications (ADMs) in Chinese patients with Type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study (2018-2024) used an Eastern China regional healthcare database. We included patients initiating GLP-1 RAs, sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), insulins, sulfonylureas, α-glucosidase inhibitors (AGIs), thiazolidinediones, or meglitinides. Outcomes were major adverse cardiovascular (MACE), kidney (MAKE), and liver (MALO) events. A propensity score-based matching weights (MWs) approach was used to balance covariates including demographics, comorbidities, and medication use, and Cox proportional hazards models were conducted in both intention-to-treat and per-protocol analyses. RESULTS: Among 105 391 patients, SGLT-2 inhibitors (HR 1.19, 95% CI 1.10-1.30), insulins (HR 1.42, 95% CI 1.32-1.52), sulfonylureas (HR 1.30, 95% CI 1.18-1.43), and AGIs (HR 1.45, 95% CI 1.31-1.59) were associated with higher MACE risk compared with GLP-1 RAs. DPP-4 inhibitors (HR 3.09, 95% CI 1.69-5.63), insulins (HR 6.11, 95% CI 4.37-8.54), and meglitinides (HR 4.56, 95% CI 2.32-8.97) were associated with higher MAKE risk. Higher MALO risk was observed with DPP-4 inhibitors (HR 1.48, 95% CI 1.21-1.79), insulins (HR 2.06, 95% CI 1.81-2.34), AGIs (HR 1.55, 95% CI 1.26-1.90), and meglitinides (HR 1.43, 95% CI 1.07-1.92). CONCLUSIONS: GLP-1 RAs were associated with favourable cardio-renal-metabolic outcomes compared with several second-line glucose-lowering agents, particularly insulins and sulfonylureas. These findings add to the real-world evidence supporting the potential cardiovascular, renal, and hepatic benefits of GLP-1 RAs in patients with T2DM.