Metabolic to Renal: A GLP-1 Signal in IgA Nephropathy with Obesity

Dr Khushboo Agarwal, Associate Professor, Endocrinology, GSVM Medical College, Kanpur

Semaglutide added to standard therapy in IgA nephropathy with obesity was associated with weight reduction and marked improvement in proteinuria, while renal function remained stable.

Obesity-related kidney disease and IgA nephropathy (IgAN) increasingly intersect in clinical practice, yet therapeutic overlap remains limited. In this reported case, a 39-year-old man with class I obesity (BMI 34 kg/m²), hypertension, dyslipidemia, fatty liver disease, and biopsy-proven IgAN with glomerulomegaly presented with persistent proteinuria despite optimized standard therapy. Baseline 24-hour proteinuria was 2373 mg/day, with preserved renal function (serum creatinine 74 μmol/L, eGFR 113.8 mL/min/1.73 m²).

Despite sequential intensification with losartan, dapagliflozin, hydroxychloroquine, and finerenone, proteinuria fluctuated and ultimately plateaued at approximately 915 mg/day. Given concomitant obesity and obesity-related glomerulopathy features, semaglutide was introduced and titrated to 0.75 mg weekly.

Within one month, proteinuria decreased to 369 mg/day, and at four months, it further decreased to 320 mg/day. This occurred alongside a 15 kg weight reduction (110 kg to 95 kg) and stable renal function. Liver enzymes and lipid profile also normalized. Gastrointestinal intolerance at higher doses required dose reduction, but treatment remained effective and generally well tolerated.

This observation aligns with emerging evidence that GLP-1 receptor agonists may reduce albuminuria beyond glycaemic control, potentially via weight loss, anti-inflammatory effects, and improvement in metabolic-renal stress pathways. However, direct disease-modifying effects in IgAN remain unproven.

While limited to a single case, these findings suggest a potential role for semaglutide in patients with IgAN and obesity, particularly when standard antiproteinuric strategies plateau. Larger, controlled studies are needed before clinical generalization.

(Reference: Li H, Jia J, Wei L, Shang W, Liu Y. Efficacy of semaglutide in IgA nephropathy with obesity: a case report. BMC nephrology. 2026 Feb 2.)