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Effects of Semaglutide Use on Obesity in Patients Undergoing Dialysis for Kidney Failure
TAKE-HOME MESSAGE
- This study evaluated the use of semaglutide for treating obesity in patients with kidney failure who were undergoing dialysis and had previously been rejected from transplant listing. All participants lost weight during the 12-week treatment, with a significant reduction in BMI. The relative intradialytic weight loss remained consistent throughout the study. Some patients responded exceptionally well to the treatment and were admitted for re-evaluation for kidney transplant listing.
- The use of semaglutide may prove to be a valuable therapeutic option for addressing obesity in patients with kidney failure. This could significantly aid in their weight loss efforts and improve their chances of being listed for kidney transplantation.
abstract
This abstract is available on the publisher's site.
Access this abstract nowAIMS
Chronic kidney disease (CKD) and obesity are major global health challenges, eventually leading to kidney replacement therapy (KRT), but body mass index (BMI) thresholds hinder kidney transplantation. Glucagon-like peptide-1 receptor agonists induce weight loss, thereby offering attractive treatment options; however, their safety and efficacy have not been systematically investigated in patients undergoing dialysis.
MATERIALS AND METHODS
We conducted a prospective 12-week, open-label trial with 13 patients who had a BMI ≥ 30.00 kg/m2, were undergoing dialysis (12 haemodialysis and 1 peritoneal dialysis) and had not been listed for transplantation due to their weight. Semaglutide was administered once weekly subcutaneously, and the dose was increased from 0.25 mg to 0.5 mg and then to 1 mg. Study endpoints included change in body weight and BMI (primary - statistically evaluated by repeated measures analysis of variance [ANOVA]), side effects, adverse events, blood parameters and patient-reported outcomes (secondary).
RESULTS
At baseline, the mean age ± standard deviation of patients was 64.0 ± 6.4 years, the mean weight was 113.9 ± 16.6 kg, and the mean BMI was 37.3 ± 3.9 kg/m2. At week 12, average weight reduction under semaglutide treatment was 4.6 ± 2.4 kg and ranged from 2.0 to 9.7 kg (p < 0.001 for weight and BMI reduction across the study period). One patient discontinued treatment due to nausea/vomiting, two patients died of unrelated causes and six patients reported side effects. Approximately 9 months after the treatment started, three patients were able to seriously reconsider being listed for transplantation.
CONCLUSIONS
Semaglutide treatment resulted in significant reduction in weight and BMI in patients with obesity undergoing dialysis, while maintaining an acceptable side effect profile comparable to that of the non-dialysis population.
Additional Info
Disclosure statements are available on the authors' profiles:
Semaglutide in patients with kidney failure and obesity undergoing dialysis and wishing to be transplanted: A prospective, observational, open-label study
Diabetes Obes Metab 2024 Oct 07;[EPub Ahead of Print], L Vanek, A Kurnikowski, S Krenn, S Mussnig, M HeckingFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Anti-obesity pharmacotherapy has revolutionized the obesity field; however, patients with renal failure have been excluded from clinical trials studying the safety and efficacy of these agents. Kidney transplant (KT) candidates with obesity, who exceed BMI thresholds set by transplant centers, are among the most in need of effective interventions. While lifestyle modifications, diet, and physical activity are essential for treating individuals with obesity, they are often insufficient for those significantly exceeding BMI limits for KT eligibility. In this context, a study conducted by Vanek and colleagues on the use of GLP-1 receptor agonists (semaglutide) in patients with stage 5 chronic kidney disease on dialysis (CKD5D) patients offers valuable insights into its safety and tolerability.
The study involved 13 KT candidates undergoing dialysis (12 on hemodialysis and 1 on peritoneal dialysis), including 6 (46%) with type 2 diabetes. Patients with a BMI of 30 kg/m² or higher were included after being rejected for kidney transplantation. Notably, many transplant centers have higher BMI thresholds for eligibility, often set at 35 kg/m² or even 40 kg/m². The mean baseline BMI was 37.3 ± 3.9 kg/m², ranging from 30.8 to 45.0 kg/m².
Semaglutide was administered subcutaneously once weekly, starting at a dose of 0.25 mg, increasing to 0.5 mg at week 4 and 1 mg at week 8, without further dose escalation. No specific dietary interventions were implemented during the study. Three patients were readmitted for kidney transplantation evaluation. Although only 8 (61.5%) patients completed the study, the results were statistically significant, with a mean weight loss of 4.6 ± 2.4 kg (n = 8, range: 2.0–9.7 kg) from a mean baseline weight of 114.6 kg (n = 12). The percentage of weight loss for those who completed the study was not reported.
In comparison, the STEP 1 trial showed that patients with obesity and without renal failure lost more than 5% of their baseline body weight after 3 months of treatment with semaglutide at a dosage of 2.4 mg per week,1 and the STEP 2 study showed a 4% weight loss after 3 months of treatment with a 1 mg per week dose in patients with type 2 diabetes.2
Adverse events were reported in 6 patients (46%), with gastrointestinal symptoms being the most common. Nausea, vomiting, and diarrhea are typical side effects of GLP-1 receptor agonists, occurring in 15% to 20% of patients with moderate-to-severe CKD (stages G3 and G4); however, their frequency was higher in the CKD5D group. Despite this, most patients did not discontinue treatment due to these symptoms. There was only one discontinuation (7.7% of the study group) after 2 days because of nausea and vomiting. Two patients died during the study period, but their deaths were not related to the study medication.
This article presents a prospective trial evaluating the use of semaglutide in KT candidates with obesity. Despite significant limitations, including a small sample size, short observation period, lower-than-maximum weight loss dose, lack of follow-up after drug discontinuation, and partially incomplete data, the findings from the prospectively collected data suggest that this treatment option may facilitate access to KT. More research is needed to explore obesity treatment approaches and the consequences of weight loss (eg, sarcopenia) in patients with CKD5D to optimize health outcomes in this group.
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