Comparative outcomes of GLP-1 receptor agonist and SGLT2 inhibitor users after liver transplantation: An emulated target trial.

Objective

We emulated a target trial to compare glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) regarding hepatic, cardiovascular, and mortality outcomes among liver transplant recipients with diabetes.

Methods

Using the TriNetX US Collaborative Network, we identified 33,161 liver transplant recipients with diabetes between 2015 and 2024. After propensity score matching, 564 pairs of new GLP-1 RA and SGLT2i users were analyzed. Risks of infection, graft rejection, cirrhosis, cardiovascular outcomes, hospitalization, and mortality were estimated using Cox proportional hazards models.

Results

The mean age was 65.8 years (SD, 10.8), and 65.1% were male. Compared with SGLT2i use, GLP-1 RA use was associated with lower risks of cirrhosis (HR, 0.787; 95% CI, 0.619-0.999), ischemic heart disease (HR, 0.721; 95% CI, 0.582-0.892), heart failure (HR, 0.502; 95% CI, 0.388-0.650), and all-cause mortality (HR, 0.622; 95% CI, 0.433-0.894). No significant differences were observed for infection, graft rejection, liver failure, or all-cause hospitalization. Sensitivity analyses generally supported the cardiovascular and mortality findings, whereas the association with cirrhosis was less consistent across propensity score models.

Conclusions

Among liver transplant recipients with diabetes, GLP-1 RA use was associated with lower risks of ischemic heart disease, heart failure, and all-cause mortality compared with SGLT2i use. A lower risk of cirrhosis was also observed, although this association was of borderline statistical significance and was not consistently significant across alternative models. Given the observational design, these findings do not establish causality and warrant prospective confirmation.