GLP-1 drugsHuman trial

Semaglutide curbs kidney vascular resistance and fibrosis

In 106 people with diabetes and kidney disease, 52 weeks of semaglutide reduced vascular resistance and stabilized markers of fibrosis compared to placebo.

Figure 1 from Nature Medicine — Figure 1Tuttle et al.

Nature Medicine4 Oct 2026, 07:20 BST

In 106 people with type 2 diabetes and chronic kidney disease, a 52-week randomized trial investigated the kidney-specific mechanisms of subcutaneous semaglutide. Participants received 1 mg of semaglutide once weekly or a placebo. Investigators evaluated tissue changes with multiparametric magnetic resonance imaging and paired pre- and post-treatment kidney biopsies for histology, single-nucleus transcriptomics, and spatial transcriptomics. Semaglutide did not significantly alter coprimary imaging measures of tissue oxygenation, global perfusion, or inflammation. However, secondary outcomes revealed that semaglutide significantly reduced the renal artery resistive index and stabilized the apparent diffusion coefficient, indicating prevention of fibrosis progression. Transcriptomic analyses revealed pronounced semaglutide-associated changes in glomerular endothelial cells, alongside fewer nearby immune cells.

Why it matters

Kidney aging is closely tied to vascular stiffening, endothelial dysfunction, and progressive fibrosis. These findings clarify how GLP-1 receptor agonists may protect microvascular health and slow structural degeneration in vulnerable kidneys.

Caveats

Semaglutide did not produce statistically significant changes in its coprimary magnetic resonance imaging endpoints. Furthermore, molecular and histological mechanisms were evaluated in smaller subsets ranging from 13 to 33 participants.