Real-World Evidence for Metformin Use in Solid Organ Transplant Recipients Living With Diabetes

Objective: Metformin is a widely used, safe, and effective antidiabetic agent; however, its use in solid organ transplant (SOT) recipients has been limited. We aimed to evaluate the safety and cardiovascular, renal, and metabolic outcomes associated with metformin use in a large, real-world cohort of SOT recipients living with diabetes. Methods: We conducted a retrospective matched-cohort study of adult SOT recipients (kidney, liver, lung, and heart) with pre-existing type 2 diabetes using data from a large health care organization. Metformin users (≥2 prescriptions post-transplant) were 1:1 matched to nonusers by age, sex, and organ type. Primary outcomes included major adverse cardiovascular events, heart failure, all-cause mortality, and severe renal dysfunction (estimated glomerular filtration rate ≤15 mL/min/1.73 m²). Secondary outcomes included metabolic changes and safety endpoints. Results: We included 938 matched patients (66% kidney, 14% liver, 16% lung, and 4% heart). Metformin use was associated with a lower risk of major adverse cardiovascular events (adjusted hazard ratio [HR] 0.77, 95% CI 0.61-0.98, P = .031) and all-cause mortality (HR 0.52, 95% CI 0.38-0.71, P < .001). In kidney recipients, metformin was associated with reduced risk of graft dysfunction (estimated glomerular filtration rate <15 mL/min/1.73 m², initiation of dialysis, kidney biopsy, or rejection; HR 0.59, 95% CI 0.45-0.77, P < .001). Glycemic and lipid parameters improved significantly in metformin users. No increased risk of lactic acidosis was observed. Conclusion: In SOT recipients living with diabetes, metformin use was associated with improved survival, cardiovascular and renal outcomes, and favorable metabolic effects without compromising safety. These findings support the cautious use of metformin in selected transplant recipients. Prospective studies are warranted.