Long-Term Safety and Renal Outcomes of Semaglutide in Non-Diabetic Obesity with Chronic Kidney Disease or Hypertension: A Systematic Review and Meta-Analysis.

Background: Semaglutide, a GLP-1 receptor agonist, has demonstrated metabolic and renal benefits in diabetic populations. However, its efficacy and safety in non-diabetic individuals with obesity and chronic kidney disease (CKD) remain largely unstudied. Given the high cardiometabolic risk in this group and limited therapeutic options, evaluating semaglutide's role is crucial. Objective: To assess the effects of semaglutide on body mass index (BMI), blood pressure, renal function (eGFR), and albuminuria in non-diabetic patients with obesity and CKD or hypertension. Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. A total of 580 studies were screened; 3 eligible studies (n=430 participants) were included. Data were extracted from a randomized controlled trial, a real-world observational dialysis study, and a large post hoc trial analysis. Fixed-effect meta-analysis models were applied to estimate pooled effects on BMI, systolic blood pressure (SBP), and renal outcomes. Results: Semaglutide treatment significantly reduced BMI (mean reduction: Tuttle 18.3%, Apperloo 11.8%, Vanek 1.5%; P = 0.001), and improved hypertension control (SBP <130 mmHg: Apperloo 20.6%, Vanek 12.5%, Tuttle 17.6%; P < 0.02). Renal function also improved, with eGFR >30 ml/min/1.73m² increasing from baseline in all studies (Apperloo 65.8%, Vanek 4.83%, Tuttle 36.4%; P < 0.001). No publication bias was detected. Conclusions: Semaglutide is effective and well-tolerated in non-diabetic patients with obesity and CKD, resulting in significant weight loss, better blood pressure control, and improved renal parameters. These findings support its expanded use in non-diabetic CKD populations, including dialysis-dependent individuals.