Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice

Background: Semaglutide, a GLP-1 receptor agonist, has shown promising nephroprotective effects in clinical trials, though real-world data on its long-term impact on renal function in high-risk diabetic nephropathy patients remain scarce. Methods: We conducted a multicenter, retrospective observational study involving 156 patients with type 2 diabetes and chronic kidney disease (CKD) treated with subcutaneous semaglutide between 2019 and 2023. Inclusion required an eGFR >15 mL/min/1.73 m² or albuminuria >30 mg/g and at least two years of follow-up. The primary outcome was the change in eGFR slope after semaglutide initiation. Subgroup analyses were performed based on baseline eGFR, albuminuria, and SGLT2i co-treatment. Results: In the whole study population, the median eGFR slope significantly improved from -3.29 (IQR 7.54) to -0.79 (IQR 6.01) mL/min/1.73 m²/year post-treatment (p< 0.001). Multiple linear regression showed a hazard ratio for the effect of semaglutide on the eGFR slope of 4.06 (2.43-5.68), p< 0.001. In patients with baseline eGFR 1,000 mg/g did not show a significant change (p=0.184). Semaglutide also reduced BMI (p=0.04), HbA1c (p=0.002), triglycerides (p=0.001), CRP (p=0.003), and GGT values (p=0.004). Conclusions: In real-world practice, semaglutide significantly attenuated renal function decline in high-risk diabetic patients, particularly those with advanced CKD or concurrent SGLT2i therapy. These findings support its nephroprotective role beyond glycemic control.