AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Type 2 Diabetic Incident Valvular Heart Disease and GLP-1RAs
By DeWitt A, Modi KA, Bhuiyan MS et al.
Background: Valvular heart disease (VHD) poses a major influence on cardiovascular mortality and morbidity worldwide. Previously, glucagon-like peptide-1 receptor agonists (GLP-1RAs) demonstrated benefits in cardiovascular health; however, their association with incident VHD remains poorly characterized. Objective: To evaluate the association between GLP-1RA use and incident VHD in adults with type 2 diabetes compared with dipeptidyl peptidase-4 (DPP-4i) inhibitors and sodium-glucose cotransporter-2 inhibitors (SGLT2i) with the All of Us Research Program database. Methods: Type 2 diabetic adults who initiated GLP-1RA, DPP-4i, or SGLT2i therapy were selected and followed for incident VHD. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Follow-up to incident VHD analyses were conducted using weighted Cox proportional hazards models for 3-, 5-, and 9-year follow-up periods. Results: The study comprised 34,655 type 2 diabetic adults (GLP-1RA: n = 5,085; DPP-4i: n = 7,416; SGLT2i: n = 22,154). At 5-year follow-up, GLP-1RA use was associated with a lower incident VHD compared with DPP-4i therapy (HR 0.66, 95% CI 0.60-0.72; p < 0.001) and SGLT2i therapy (HR 0.47, 95% CI 0.43-0.50; p < 0.001). These findings remained consistent across the 3-year (HR 0.67, 95% CI 0.60-0.76) and 9-year follow-up periods (HR 0.81, 95% CI 0.76-0.87) when compared with DPP-4i therapy. Conclusions: In this target trial emulation of adults with type 2 diabetes, GLP-1RA use was associated with a significantly lower incident VHD compared with both DPP-4i and SGLT2i therapies. These findings suggest that future investigation is needed to develop and warrant further potential of a protective association of GLP-1RAs against VHD.