Abstract: FR-OR102
Effects of Semaglutide on Kidney Parameters in Patients with Obesity and Nondiabetic CKD
Session Information
- High-Impact Clinical Trials - 1
October 25, 2024 | Location: Hall D, Convention Center
Abstract Time: 11:15 AM - 11:30 AM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Heerspink, Hiddo Jan L., Universiteit Groningen Faculteit Medische Wetenschappen, Groningen, Groningen, Netherlands
- Apperloo, Ellen M., Universiteit Groningen Faculteit Medische Wetenschappen, Groningen, Groningen, Netherlands
- Jongs, Niels, Universiteit Groningen Faculteit Medische Wetenschappen, Groningen, Groningen, Netherlands
- Cigarran, Secundino, Hospital Ruber Internacional, Madrid, Madrid, Spain
- Soler, Maria Jose, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain
- Cruzado, Josep M., Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- van der Aart, Annemarie B., Martini Ziekenhuis, Groningen, Groningen, Netherlands
- Laverman, Gozewijn Dirk, Ziekenhuisgroep Twente, Almelo, Overijssel, Netherlands
- Verhave, Jacobien, Rijnstate, Arnhem, Gelderland, Netherlands
- Ahmed, Sofia B., University of Alberta, Edmonton, Alberta, Canada
- Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Wanner, Christoph, Universitatsklinikum Wurzburg Deutsches Zentrum fur Herzinsuffizienz, Wurzburg, Bayern, Germany
- Cherney, David, University of Toronto, Toronto, Ontario, Canada
- Gorriz, Jose L., Universitat de Valencia, Valencia, Spain
Background
Semaglutide is a glucagon like peptide 1 receptor agonist which reduces albuminuria and the risk of kidney failure in patients with type 2 diabetes and chronic kidney disease (CKD). We assessed the effects of semaglutide in patients with overweight/obesity and albuminuric CKD without diabetes.
Methods
We conducted a multicenter randomized placebo-controlled clinical trial in adults with CKD (eGFR ≥25 mL/min/1.73m2, urine albumin-to-creatinine ratio [UACR] ≥30 and <3500 mg/g), body mass index ≥27 kg/m2 and HbA1c <6.5% without use of hypoglycemic agents. Participants were randomized to 24 weeks treatment with subcutaneous semaglutide 2.4 mg/week or placebo adjunctive to renin-angiotensin-system inhibition when indicated. The primary endpoint was percentage change from baseline in UACR at week 24. Secondary endpoints included change in iohexol measured GFR, estimated GFR, body weight, and systolic blood pressure (BP). Safety was monitored throughout.
Results
Of 125 screened participants, 101 were randomized to semaglutide or placebo. Mean age was 55.8 (SD 12) years, 40 (39.6%) were female, median UACR was 251 mg/g (IQR 100, 584), eGFR 65.0 (SD 25) mL/min/1.73m2. Chronic glomerulonephritis (N=25) and hypertensive CKD (N=27) were the most common CKD etiologies. At week 24, the placebo-corrected geometric mean change from baseline in UACR with semaglutide was -52.1% (95%CI -65.2, -34.1; p<0.0001). Compared to placebo, mGFR was changed at week 24 with semaglutide by -1.9 mL/min/1.73m2 (95%CI -8.0, 4.3). Corresponding changes in eGFR-creatinine and eGFR-cystatin C were -1.1 (95%CI -4.8, 2.6) and +2.1 mL/min/1.73m2 (95%CI -1.7, 5.9), respectively. Semaglutide compared to placebo changed body weight by -9.1 kg (95%CI -11.1, -7.1) and systolic BP by -6.3 mmHg (95%CI -11.1, -1.5). Gastrointestinal adverse events were more often reported in the semaglutide (N=30) versus placebo group (N=15).
Conclusion
Treatment with semaglutide for 24 weeks in patients with overweight/obesity and CKD without diabetes resulted in a robust and clinically meaningful reduction in UACR. These results support further trials to assess long-term efficacy and safety of semaglutide in these patients.
Funding
- Commercial Support – Novo Nordisk provided a grant to the University Medical Center Groningen to conduct this investigator initiated clinical trial