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o In September 2025, Rybelsus (oral semaglutide) received an EU label update based on the SOUL trial, making it the first and only oral GLP-1 RA with proven cardiovascular benefits, having demonstrated a 14% reduction in cardiovascular death, heart attack, and stroke in high-risk type 2 diabetes patients

In DKD, continuous activation of RAAS leads to elevated pressure within the glomeruli, enhances the production of ROS, promotes tissue damage, triggers the release of proinflammatory cytokines, and stimulates the development of fibrosis in the glomeruli and tubulointerstitium

the frequency of these reactions is unknown

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Tillmann T., Kamino K., Dasenbrock C., Ernst H., Kohler M., Morawietz G., Campo E., Cardesa A., Tomatis L., Mohr U

For example, MTHFR gene variants and transcobalamin mutations can play a role