Short-Term Treatment Response Outcomes of Semaglutide Combined With Dapagliflozin in Overweight or Obese Patients With Early Diabetic Nephropathy

Background: Diabetic nephropathy (DN) is a major microvascular complication of type 2 diabetes mellitus (T2DM), and overweight/obesity may further accelerate the progression of albuminuria and metabolic deterioration. In overweight or obese patients with early DN, short-term evidence on semaglutide combined with dapagliflozin in real-world practice remains limited. Methods: A retrospective analysis was conducted on 120 overweight/obese patients with T2DM and early DN treated in the Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University, from March 2022 to June 2025. In the original cohort, 65 patients received dapagliflozin monotherapy and 55 received semaglutide combined with dapagliflozin. After 1:1 propensity score matching, 55 matched pairs were included in the final comparative analysis, and all subsequent efficacy and safety analyses were performed in this matched cohort. All 110 matched patients completed the 3-month follow-up, with no missing data identified for the core study variables. Blood glucose indices, body mass index (BMI), lipid parameters, renal-related biomarkers, including estimated glomerular filtration rate (eGFR), treatment response outcomes, and adverse reactions, were compared before and after treatment. Results: After 3 months of treatment, fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin decreased in both groups. Compared with the control group, the observation group had lower post-treatment fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin levels (all p < 0.05). Post-treatment BMI, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also lower in the observation group than in the control group (all p < 0.05). For renal-related biomarkers, the observation group showed lower post-treatment blood urea nitrogen and urinary albumin-to-creatinine ratio levels and a higher eGFR than the control group (all p < 0.05), whereas the between-group difference in post-treatment serum creatinine was not statistically significant (p > 0.05). In addition, the observation group showed a higher glycated hemoglobin A1c (HbA1c) target achievement rate, a greater percentage decrease in urinary albumin-to-creatinine ratio (UACR), and a larger reduction in BMI than the control group (all p < 0.05). No statistically significant difference was found in the overall incidence of adverse reactions between the two groups (p > 0.05). Conclusion: In overweight or obese patients with T2DM complicated by early DN, semaglutide combined with dapagliflozin was associated, over a 3-month follow-up period in the matched cohort, with lower post-treatment glucose, BMI, and lipid levels, a higher HbA1c target achievement rate, a greater percentage decrease in UACR, and more favorable short-term changes in renal-related biomarkers than dapagliflozin monotherapy, without a significant increase in adverse reactions.