SUN-591 GLP1-RA, SGLT2i and Risk of Advanced Fibrosis in Patients with T2D:a Target Trial Emulation

Abstract Disclosure: A. Turchin: Eli Lilly & Company, Research support, Novo Nordisk, Consulting. L. Petito: None. E. Hegermiller: None. R. Carnahan: None. A. DeVries: None. S. Goel: None. M. Lansang: Abbott Laboratories, Research support, Dexcom, Research support. M.E. McDonnell: Dexcom. V. Nair: None. E. Priest: AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company. V. Willey: None. A. Kaul: None. R. Chung: None. Background: Several studies have shown that patients with T2D and MASLD can benefit from treatment by GLP1-RA or SGLT2i. It is not known whether these medications can prevent advanced liver pathology in individuals without known advanced pre-existing liver disease. Methods: We emulated a target trial using nationwide dataset from 12 US health systems and insurance plans for patients with T2D at moderate CV risk, hyperglycemia (HbA1c 7.0-11.0%) and with eGFR ≥ 45 ml/min/1.73m2 who initiated a second T2D medication after metformin between 1/1/13 and 12/31/22. Patients with a history of hepatitis B or C or alcohol use disorder were excluded, as were patients who reached the primary outcome endpoint prior to treatment initiation. We compared patients initiating a) SGLT2i; b) GLP1-RA; or c) sulfonylureas to patients initiating DPP4i. We estimated 5-year risk of a composite advanced MASH outcome (diagnosis of MASH or FIB-4 score > 2.67) after adjustment for demographics, comorbidities and laboratory values. Results: We studied 67,722 patients followed for a median of 31 (IQR 17-56) months, with a median age of 60 (IQR 51-68) years and median baseline HbA1c of 7.8% (IQR 7.3-8.5%); 32,789 (48.4) were women. Their median FIB-4 score was 1.04 (IQR 0.79-1.37) and 2489 (3.7%) had MASLD at baseline. Of these, 11,338 patients initiated a GLP1-RA; 11,751 initiated an SGLT2i; 32,286 initiated a sulfonylurea; and 12,347 patients initiated a DPP4i. A total of 3,384 (5.0%) of patients experienced the primary outcome endpoint. In the analysis adjusted for baseline sociodemographic characteristics, BMI, FIB-4, HbA1c and comorbidities, including a diagnosis of MASLD, the estimated 3-year risk ratios (95% CI), compared to DPP4i, were 0.84 (0.72 - 0.97) for GLP1-RA, 0.88 (0.76, 0.99) for SGLT2i and 0.98 (0.89, 1.07) for sulfonylureas. Evaluation of the relationship between treatment group and the primary outcome across subgroups defined by sex, age, and HbA1c showed similar point estimates with largely overlapping confidence intervals. Conclusions: Patients with T2D treated with a GLP1-RA or an SGLT2i as a second agent after metformin had a lower risk of MASH / advanced liver fibrosis compared with patients treated with DPP4i. Presentation: Sunday, July 13, 2025