Semaglutide May Effectively Treat Non-Diabetic Nephropathy, Study Finds

Results from a recent study have indicated that semaglutide may serve as an effective therapeutic option for patients who have immunoglobulin A (IgA) nephropathy and overweight or obesity without diabetes who are undergoing conventional treatment regimens.

Glucagon-like peptide-1 receptor agonist (GLP-1RA) can significantly decrease the risk of cardiovascular events in patients with or without diabetes. Prior research has indicated that semaglutide, a GLP-1 analogue, effectively reduces body weight by a mean of 15.2% among patients with overweight or obesity who did not have diabetes.2

Additionally, semaglutide has displayed renoprotective effects in patients with diabetes and chronic kidney disease. Investigators believe potential mechanisms for these effects may include oxidative stress reduction, inflammation, and fibrosis in the kidney.1

“This is the first real-world report assessing semaglutide in the treatment of non-diabetic IgAN with overweight or obesity,” wrote Feng-Lei Si, Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, and colleagues. “Broth proteinuria and body weight demonstrated consistent reductions following semaglutide administration. Notably, consistent with previous research, a reduction in eGFR was observed one month after initiating treatment.”1

The study collected 8 patients with primary IgAN – 6 of these patients were classified as obese (body mass index [BMI] ≥28 kg/m2) and two as overweight (BMI ≥24 kg/m2). Average proteinuria at baseline was recorded as 1.55 +/- .84 g/d. Three patients were at chronic kidney disease (CKD) stage 2 or higher, three at stage 3, and two at stage 4. Most patients had been prescribed renin-angiotensin system inhibitors (RASi) (100%), sodium-glucose transporter 2 inhibitors (SGLT2i) (62.5%), and hydroxychloroquine (HCQ) (37.5%); all these treatments were used ≥3 months before semaglutide therapy began.1

Si and colleagues noted a substantial reduction in proteinuria levels in most patients, from 1.55 +/- .84 to .97 +/- .64 g/d at 3 months (P = .027). The median proteinuria reduction was -40.6% (-66.3%, -8.7%). Weight loss was also noted in all cases, from 86.7 +/- 12.1 to 82.1 +/- 13.1 kg at 3 months (P = .002), with a reduction percentage of -4% (-8%, -2.7%). Estimated glomerular filtration rate was stable for most patients, only decreasing slightly from 58.6 +/- 30.74 to 52.75 +/- 23.86 mL/min/1.73 m2 at 3 months (P = .144).1

Importantly, although mild diarrhea occurred in 2 patients following semaglutide treatment initiation, no patients discontinued therapy due to safety concerns. No serious adverse events were reported at any point throughout the study.1

Although these data suggest an overall success, investigators caution that results may be compromised by the limited sample size and short follow-up period. Whether improvement will continue after one month is uncertain; Si and colleagues invite future studies with larger sample sizes and longer observation periods to evaluate long-term renal effects.1

Additionally, investigators noted that patients were treated with both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) simultaneously if they exhibited high levels of proteinuria or difficult-to-control blood pressure. Combining these therapies, however, is not recommended.1

“This pilot study indicates that semaglutide could serve as an effective therapeutic option for overweight or obese non-diabetic patients with IgA nephropathy who are undergoing conventional treatment regimens,” Si and colleagues wrote. “A high-quality study with a larger patient population and longer follow-up durations will be necessary in the future.”1

References

1. Si F, Tang C, Chen P, et al. Effectiveness of semaglutide in overweight or obese patients with iga nephropathy without diabetes. Nephrology. 2025;30(4). doi:10.1111/nep.70023

2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563