Published online Feb 15, 2026. doi: 10.4239/wjd.v17.i2.112867
Revised: October 28, 2025
Accepted: December 11, 2025
Published online: February 15, 2026
Processing time: 164 Days and 0.8 Hours
Diabetic nephropathy (DN) is a major microvascular complication of type 2 diabetes and a leading cause of end-stage renal disease. Both canagliflozin and semaglutide are recommended for diabetic nephropathy, yet direct evidence comparing their combination versus monotherapy remains lacking.
To investigate the efficacy of combination therapy with semaglutide and canag
A retrospective study was conducted using data sourced from the electronic medical record system of Henan Provincial People’s Hospital. The study included patients with DN treated from October 2022 to March 2024. Patients were divided into two groups on the basis of their treatment: Canagliflozin monotherapy (CM) and canagliflozin and semaglutide combination therapy (CSCT). Renal function, glucose metabolism, lipid profiles, pancreatic function, oxidative stress, and inflammatory markers were assessed at baseline and 6 months after treatment. Adverse events were monitored throughout the study period.
Among 211 patients (107 CM, and 104 CSCT), the CSCT group demonstrated superior outcomes. The albumin-to-creatinine ratio decreased more significantly (145.87 mg/g vs 158.11 mg/g, P = 0.002), and more improvements were found in the glycated hemoglobin A1c (7.08% vs 7.42%, P = 0.005), low-density lipoprotein (86.74 mg/dL vs 94.86 mg/dL, P = 0.032), serum free fatty acids (0.46 mmol/L vs 0.52 mmol/L, P = 0.002), and insulin resistance index (3.94 vs 4.08, P = 0.011). Meanwhile, the islet β-cell function increased (51.22 vs 49.36, P = 0.022). The total adverse event rates were comparable between the two groups, and no significant increase was observed in the gastrointestinal adverse events (P = 0.360).
CSCT provided significant improvements in multiple metabolic and renal parameters without increasing adverse events, thus highlighting its potential benefits for patients with DN.
Core Tip: This retrospective study demonstrates that, in individuals with type 2 diabetes and nephropathy, the addition of semaglutide to canagliflozin monotherapy provides better renal protection and metabolic improvements compared to canagliflozin alone. The combination significantly reduced proteinuria, improved glycemic and lipid control, enhanced β-cell function, alleviated systemic inflammation and oxidative stress, without increasing adverse events. It offers an effective and safe intensification therapy option, particularly for those who have not achieved optimal levels of proteinuria or metabolic parameters under sodium-glucose cotransporter-2 inhibitor monotherapy.