Glucagon-like Peptide-1 Receptor Agonists in Heart Transplant Recipients With Type 2 Diabetes: A Multicenter Study

BACKGROUND: Type 2 diabetes mellitus (T2DM) is frequent after heart transplantation (HT) and is exacerbated by immunosuppressive therapy. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve metabolic control, but data in HT recipients are limited. METHODS: We performed a retrospective, multicenter study including HT recipients with T2DM from 14 Spanish centers. In patients treated with GLP-1 RAs, we assessed antidiabetic and immunosuppressive therapies, adverse events, and changes in metabolic parameters, insulin dose, and immunosuppressant trough levels during the first year after GLP-1 RA initiation. RESULTS: Among 734 HT recipients with T2DM (2011-2021), 108 (14.7%) received GLP-1 RAs (mean age 55.4 ± 9.0 y; 79.6% male), initiated 4.0 ± 3.1 y post-HT. At baseline, 64.8% had obesity. Semaglutide was used in 59%, dulaglutide in 27%, liraglutide in 13%, and tirzepatide in 1%; 41.7% achieved the maximum therapeutic dose. After 1 y, significant reductions were observed in body weight (-6.2 kg; 95% confidence interval [CI], -7.7 to -4.5 kg), fasting glucose (-27 mg/dL; 95% CI, -41 to -7 mg/dL), glycated hemoglobin (-0.74%; 95% CI, -1.12% to -0.35%), total cholesterol (-12 mg/dL; 95% CI, -19 to -6 mg/dL), low-density lipoprotein cholesterol (-8 mg/dL; 95% CI, -14 to -2 mg/dL), triglycerides (-29 mg/dL; 95% CI, -53 to -5 mg/dL), and systolic blood pressure (-3.6 mm Hg; 95% CI, -6.4 to -0.9 mm Hg). Tacrolimus trough levels decreased modestly (-0.7 ng/mL; 95% CI, -1.4 to -0.1 ng/mL; P = 0.025), without episodes of acute rejection. Gastrointestinal adverse events occurred in 12.0%, leading to discontinuation in 3.7%. CONCLUSIONS: In HT recipients with T2DM, GLP-1 RAs were associated with improved glycemic and cardiometabolic parameters and were generally well tolerated. These findings support the use of GLP-1 RAs as a valuable therapeutic strategy for the management of T2DM after HT.