Safety and Efficacy of Glucagon Like Peptide-1 Receptor Agonism-Based Therapies in End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: No systematic review and meta-analysis has analyzed the safety and efficacy of glucagon like peptide-1 receptor agonism-based therapies (GLP1RA-BTs) in people with end stage renal disease (ESRD) [GFR<15 ml/min/1.73 m or on renal replacement therapy]. Hence this systematic review and meta-analysis analyzed the safety and efficacy of GLP1RA-BT in ESRD. METHODS: Electronic databases were searched for articles evaluating the use of GLP1RA-BT in ESRD. Primary outcome was mean reduction in body weight from baseline following treatment with GLP1RA-BT. Secondary outcomes were changes in body mass index (BMI), glycaemia, and safety profile. RESULTS: Data from 388 patients [semaglutide(266), liraglutide(66), dulaglutide(47), and tirzepatide(9); 19 studies] with ESRD (91.5% on renal replacement therapy) having baseline weight, BMI, and glycated hemoglobin of 97.7 ± 23.8 kg, 34.4 ± 6.8kg/m2, and 7.26 ± 1.53%, respectively were analyzed. Weight reduction with semaglutide after 3-, 6-, and 12-months therapy were -3.09 kg (95% confidence interval [CI]: -5.95, -0.24; I = 58.1%), -3.68 kg (95% CI: -5.71, -1.65; I = 0.0%), and -7.00 kg (95% CI: -11.38, -2.61; I = 79.2%), respectively. BMI reduction with semaglutide after 3-, 6-, and 12-months therapy were -1.42 kg/m (95% CI: -2.92, 0.09; I = 0.0%), -1.26 kg/m (95% CI: -1.90, -0.62; I = 0.0%), and -3.09 kg/m (95% CI: -5.28, -0.89; I = 95.9%), respectively. Pooled glycated hemoglobin reduction with semaglutide after 6 and 12 months of therapy were -0.50% (95% CI: -1.20, 0.20; I = 0.0%) and -0.75% (95% CI: -1.07, -0.43; I = 61.6%), respectively. Pooled body-weight reduction with liraglutide after 3 and 6 months therapy were -2.24 kg (95% CI: -7.73, 3.26; I = 0.0%) and -4.50 kg (95% CI: -11.26, 2.27; I = 0.0%), respectively. With semaglutide, total adverse events (AEs) occurred in 44% patients (95% CI: 24%, 66%; I = 58.3%). Gastrointestinal AEs were observed in 39% (95% CI: 25%, 55%; I = 48.8%), including nausea in 36% (95% CI: 3%, 91%; I = 73.6%) and vomiting in 13% (95% CI: 2%, 53%; I = 0.0%). Hypoglycaemia occurred in 9% (95% CI: 0%, 82%; I = 0.0%). Discontinuation due to AEs was observed in 9% (95% CI: 4%, 20%; I = 60.3%). CONCLUSION: GLP1RA-BT specifically semaglutide, may be considered for use in ESRD. The results are primarily hypothesis generating, and prospective RCTs are urgently needed.