# Effectiveness of Pre‐Transplant Dual GLP‐1 Receptor Agonist and SGLT2 Inhibitor Therapy on All‐Cause Mortality in Organ Transplantation Candidates with Obesity and Type 2 Diabetes: a Target‐Trial Emulation

## TL;DR

Using a combination of two diabetes drugs before organ transplant may reduce mortality in obese patients with type 2 diabetes.

## Contribution

This study evaluates dual GLP-1 RA and SGLT2i therapy's impact on transplant outcomes using a target-trial emulation.

## Key findings

- Dual therapy was associated with lower 12-month mortality compared to GLP-1 RA, SGLT2i, and usual care.
- Lower mortality estimates were consistent across sensitivity analyses at 24 and 36 months.
- Infection rates were neutral or lower with dual therapy.

## Abstract

Evidence on pre‐transplant metabolic therapy remains limited. We evaluated whether concurrent glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) plus sodium–glucose cotransporter 2 inhibitor (SGLT2i) use before solid‐organ transplantation was associated with post‐transplant outcomes in adults with obesity and type 2 diabetes. A target trial is emulated using de‐identified electronic health records from TriNetX US. Dual therapy is compared with GLP‐1 RA, SGLT2i, and usual care using 1:1 propensity‐score matching. The primary outcome is all‐cause mortality at 12 months; kidney graft failure, rejection, complications, and infections are secondary. Sensitivity analyses included the global network, landmark, extensions at 24 and 36 months. Three matched cohorts are constructed, dual versus GLP‐1 RA (n = 4718 pairs), dual versus SGLT2i (n = 4282), and dual versus usual care (n = 3787). At 12 months, dual therapy is associated with lower mortality versus GLP‐1 RA (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.57–0.85), SGLT2i (0.59, 0.48–0.72), and usual care (0.52, 0.43–0.64). Infection endpoints are neutral or lower. Estimates are consistent across sensitivity analyses. In transplant candidates with obesity and type 2 diabetes, pre‐transplant GLP‐1 RA+SGLT2i use is associated with lower mortality than monotherapy or usual care. Prospective evaluation is warranted.

This target trial emulation in solid organ transplant candidates with obesity and type 2 diabetes evaluates whether pre‐transplant dual therapy with GLP‐1 receptor agonists plus SGLT2 inhibitors is associated with post‐transplant mortality and kidney graft outcomes compared with monotherapy or usual care, using multinational electronic health records and extensive sensitivity analyses.