Semaglutide curbs renal vascular resistance and fibrosis in phase 2 trial

Researchers have identified specific cellular and vascular mechanisms through which the GLP-1 receptor agonist semaglutide protects kidney function in adults with type 2 diabetes and chronic kidney disease, according to nature.com nature.comnature.comnature.comOpen source ↗. The randomized REMODEL trial enrolled 106 participants across 28 sites in eight countries between April 2021 and October 2023. Patients received either 1 mg of subcutaneous semaglutide or a placebo once weekly for 52 weeks to assess renal physiological and molecular responses.

Imaging and hemodynamic outcomes

The trial's coprimary endpoints evaluated kidney oxygenation via R2* mapping, global tissue perfusion, and tissue inflammation using MRI T1 mapping. Over the 52-week treatment period, these coprimary measures did not show statistically significant differences between the semaglutide and placebo cohorts. However, secondary hemodynamic outcomes demonstrated a statistically significant decrease in the renal artery resistive index among patients receiving semaglutide. Furthermore, apparent diffusion coefficient values stabilized, indicating prevention of kidney fibrosis progression.

Transcriptomic and cellular profiling

To capture structural changes, investigators analyzed paired kidney biopsies collected before and after treatment from 33 participants. Single-nucleus RNA sequencing on 22 samples and spatial transcriptomics on 13 samples indicated pronounced regulatory changes in glomerular endothelial cells. Spatial analyses confirmed a reduction in the density of inflammatory immune cells in close proximity to these endothelial cells. The authors concluded that semaglutide's therapeutic effects involve lowering vascular resistance, preserving tissue integrity, and maintaining microvascular health.