All studies mentioned in the article are referenced below.
Chronic kidney disease (CKD) costs over $100 billion USD every year, yet effective therapies remain sparse. Into this fiscal and human crisis steps the glucagon-like peptide-1 (GLP-1) receptor axis, a metabolic signal which may prove to be a renal survival pathway.
A study by Heerspink et al. (2024), set out to test whether semaglutide helps people with obesity-related CKD who do not have diabetes. In just 24 weeks the weekly injection halved urinary albumin, while weight and blood-pressure fell in parallel. Albumin in the urine is not just a marker; it actively scars kidney tubules, so a 52 % drop is clinically meaningful. For practice, the finding urges nephrologists to check UACR early and consider adding a GLP-1 agent when renin–angiotensin blockers and SGLT2 inhibitors leave residual leak, reinforcing the centrality of the GLP-1 receptor axis.
The ongoing REMODEL trial Bjornstad et al. (2022) tackles the “how.” By combining oxygen-sensitive MRI sequences with kidney biopsies, investigators aim to show that semaglutide re-oxygenates the renal cortex and calms inflammation – two processes long thought irreversible. If imaging confirms better perfusion after 52 weeks, guidelines may soon endorse GLP-1 therapy not only for weight or glucose but as a targeted antidote to kidney hypoxia, again spotlighting the GLP-1 receptor motif.
Another study, by Perkovic et al. (2024), translated biomarkers into events. Among 3,533 adults with diabetes and CKD, semaglutide lowered the risk of kidney failure, steep eGFR loss or death by 24 % over 3.4 years—while also trimming cardiovascular deaths by nearly a third. Importantly, the eGFR slope slowed by over one millilitre per year, a magnitude comparable to today’s gold-standard SGLT2 inhibitors. Clinically, every 10 patients treated for three years might spare one dialysis start, strengthening the case for pairing GLP-1 and SGLT2 drugs along the same molecular highway.
SELECT’s kidney analysis conducted by Colhoun et al. (2024) extends the story to people without diabetes but with cardiovascular disease. The drug cut the composite kidney endpoint by 22 %, and mediation modelling suggested that four-fifths of the eGFR benefit rode on weight loss rather than blood sugar or pressure. The take-home: the GLP-1 receptor can be leveraged as a weight-sensing rheostat to unload glomeruli, arguing for integrated cardio-renal-obesity clinics.
Finally, the 2024 placebo-controlled trial in nondiabetic CKD by Apperloo et al. (2024) reaffirmed the UACR halving seen in the study by Heerspink et al. (2024) and showed the effect was consistent across glomerulonephritis, hypertensive nephropathy, and obesity-related glomerulopathy. Transient eGFR dips resolved, echoing the benign “hemodynamic reset” seen with SGLT2 therapy. For researchers, the trial signals that the GLP-1 receptor axis is agnostic to CKD etiology, inviting exploration in autoimmune and hereditary kidney diseases.
In conclusion, a clear pattern in the research can be observed that activating the GLP-1 receptor shrinks albuminuria and slows long-term eGFR loss, in both diabetic and non-diabetic kidneys. Mechanistically, there seem to be benefit such as improved cortical oxygenation, dampened inflammation, better weight control and lower intraglomerular pressure. However, further research must be conducted to answer if the benefits are long-lasting, if MRI or biopsy markers can predict what patients will most benefit from such treatment, or what the optimal sequence or combination with established therapies is for effective patient care and treatment.
References:
Apperloo EM, Gorriz JL, Soler MJ, et al. Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. Nat Med. 2025;31(1):278-285. doi:10.1038/s41591-024-03327-6
Bjornstad P, Cherney D, Lawson J, et al. MO399: Remodel: A Mechanistic Trial Evaluating the Effects of Semaglutide on the Kidneys In People With Type 2 Diabetes and Chronic Kidney Disease. Nephrology Dialysis Transplantation. 2022;37(Supplement_3):gfac070.013. doi:10.1093/ndt/gfac070.013
Colhoun HM, Lingvay I, Brown PM, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30(7):2058-2066. doi:10.1038/s41591-024-03015-5
Heerspink HJL, Apperloo EM, Jongs N, et al. Effects of Semaglutide on Kidney Parameters in Patients with Obesity and Nondiabetic CKD: FR-OR102. Journal of the American Society of Nephrology. 2024;35(10S). doi:10.1681/ASN.20242wv2xw41
Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347
AI-Assisted Content Disclaimer: Portions of this article were generated with the help of artificial-intelligence tools that located the peer-reviewed studies referenced and summarized their key findings. Our aim in using AI is to explore how these technologies can enhance medical research translation and reporting, and to assess their effectiveness in advancing evidence-based practice. Human experts reviewed and edited all material to ensure accuracy and clarity. For more information about our AI workflows, please email us at the address provided.
Svasth 
Leave a comment