The Use of Semaglutide in Patients with Renal Failure- a Retrospective Cohort Study

Objective Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with eGFR (estimated glomerular filtration rate) 15–29 mL/min/1.73m2 (CKD stage 4), eGFR<15 mL/min/1.73m2 (CKD stage 5) or on dialysis. Methods This is a retrospective Electronic Medical Record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between Jan 2018 and Jan 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher’s exact test, paired T-test, linear mixed effects models and Wilcoxon signed rank test. Results Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of T2DM (96.0%), and most were male (53.9%). The mean age was 66.8 y (SD 11.5) with the mean BMI was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2(SD 24.2) to 101.3 (SD 27.3) kg (p<0.001). Eight patients (16%) with type 2 diabetes (T2DM) discontinued insulin after starting semaglutide. Mean HbA1c decreased from 8.0 % (SD 1.7) to 7.1 % (SD 1.3) (p<0.001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. Conclusions Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6 % of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.