Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis

Abstract

Background Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. Method A comprehensive literature search was conducted in MEDLINE, EMBASE, and Cochrane Database from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycemic and metabolic parameters, weight, cardiovascular outcomes, and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Results Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (IQR 6, 23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate (eGFR) (SMD of −0.07 ml/min/1.73m2; 95% CI −0.64, 0.50) or creatinine (SMD of −0.08 mg/dL; 95% CI −0.44, 0.28), they were associated with a significant decrease in urine protein-to-creatinine ratio of SMD −0.47 (95% CI −0.77, −0.18) and HbA1c levels with MD of −0.85% (95% CI −1.41, −0.28). Total daily insulin dose, weight, and body mass index also decreased significantly. Tacrolimus levels remained stable with MD of −0.43 ng/mL (95% CI −0.99, 0.13). Side effects primarily encompassed nausea and vomiting (17.6%), diarrhea (7.6%), and injection site pain (5.4%). Conclusions and relevance GLP-1RAs are effective in reducing proteinuria, improving glycemic control, and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.