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.

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.