Effects of semaglutide on kidney disease in type 2 diabetes: a randomized placebo-controlled trial
In brief
Semaglutide lowered kidney vascular resistance, but primary MRI measures stayed unchanged
In a 52-week randomized trial of 106 people with type 2 diabetes and chronic kidney disease, semaglutide did not change the primary MRI measures of kidney oxygenation, blood flow or inflammation. Secondary findings included lower vascular resistance and stabilization of a measure linked to fibrosis, alongside signs of healthier endothelial-cell activity; whether these changes translate into better long-term kidney outcomes remains unknown.
- Journal
- Nature medicine (Q1)
- Published
- 1 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Katherine R Tuttle, Petter Bjornstad, Cathy Smith, Menno Pruijm, Phillip J McCown, Jeffrey B Hodgin, et al.
- PMID
- 42823485
- DOI
- 10.1038/s41591-026-04674-2
Why clinicians should know about it
- Picked for Histology (top studies of the week, 4 October 2026): Kidney biopsy mechanistic, not normal histology
- Picked for Nephrology (top studies of the week, 4 October 2026): Randomized placebo-controlled trial of semaglutide in CKD patients
Abstract
The GLP-1 receptor agonist semaglutide preserves kidney function in people with type 2 diabetes and chronic kidney disease, but the underlying mechanisms are unclear. Here we report a 52-week randomized trial of subcutaneous semaglutide 1 mg once weekly versus placebo (n = 106 (n = 25 women, n = 81 men)) in participants with type 2 diabetes and chronic kidney disease. To identify kidney-specific mechanisms of action for semaglutide, we performed integrated multiparametric magnetic resonance imaging of the kidney and biopsy for histology (n = 33), alongside single-nucleus (n = 22) and spatial transcriptomics (n = 13) on paired samples with before- and after-treatment measurements. Coprimary magnetic resonance imaging outcomes (oxygenation by R2*, global perfusion and tissue inflammation by T1 mapping) were not significantly altered by semaglutide versus placebo treatment. Secondary outcomes revealed that semaglutide treatment, as compared to placebo, was associated with a significantly reduced renal artery resistive index and stabilization of the apparent diffusion coefficient, indicating prevention of fibrosis progression. Moreover, secondary transcriptomic outcomes revealed pronounced effects of semaglutide on glomerular endothelial cells, consistent with the results of spatial analyses indicating reduced numbers of immune cells in the proximity of these endothelial cells. The results from this trial indicate that mechanisms of kidney protection by semaglutide may include reduced vascular resistance, prevention of fibrosis and improved underlying molecular programs promoting endothelial cell health. ClinicalTrials.gov identifier: NCT04865770 .
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.