Clinical efficacy, safety, and predictors of treatment response to SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a retrospective comparative study

Background The prevalence of type 2 diabetes is continuously increasing, and optimizing the treatment strategies for diabetes is an important clinical issue. SGLT2 inhibitors (SGLT2i) and DPP-4 inhibitors (DPP-4i) are two commonly used oral hypoglycemic drugs, and their comprehensive efficacy and safety profiles in real-world settings merit in-depth comparison. Objective To compare the clinical efficacy and safety of SGLT2i and DPP-4i in treating patients with type 2 diabetes from May 2024 to August 2025, and to explore the predictive factors influencing treatment response. Method A retrospective cohort study was conducted using medical records of 100 patients with type 2 diabetes who met standardized screening criteria. These patients were assigned to two treatment groups: the SGLT2 inhibitor group (SGLT2i, n=50) and the DPP-4 inhibitor group (DPP-4i, n=50). Primary endpoints comprised changes in glycated hemoglobin (HbA1c) levels and the occurrence of major adverse cardiovascular events. Secondary outcomes including changes in body mass index, blood pressure, renal function parameters (urinary albumin-to-creatinine ratio and estimated glomerular filtration rate), lipid profile, liver function markers, and the frequency of adverse events. Exploratory measures, including inflammatory markers such as C-reactive protein, were also evaluated. Statistical analyses were performed using SPSS, including t-tests, chi-square tests, and multivariate logistic regression. Results Regarding primary outcomes, comparable reductions in HbA1c were observed in both groups. In terms of safety profiles, the SGLT2i group exhibited a significantly lower rate of major adverse cardiovascular events compared to the DPP-4i group (2.00% vs. 16.00%, P < 0.05). A higher incidence of genital infections was noted in the SGLT2i group (14.00% vs. 2.00%), whereas no statistically significant difference was found in hypoglycemia events between the two groups. For secondary outcomes, patients receiving SGLT2 inhibitors demonstrated significantly greater improvements in body weight reduction, systolic blood pressure lowering, and urinary albumin-to-creatinine ratio compared to the DPP-4i group ( P < 0.05). Multivariate Logistic regression analysis showed that SGLT2 inhibitor treatment (OR = 1.747, 95% CI: 1.137 - 2.684, p = 0.011), diastolic blood pressure (OR = 0.827, 95% CI: 0.694 - 0.985, p = 0.033), history of hypertension (OR = 0.010, 95% CI: 0.001 - 0.121, p < 0.001), and total bilirubin (OR = 1.956, 95% CI: 1.091 - 3.507, p = 0.024) were all independent influencing factors for the glucose treatment response. Conclusion In patients with type 2 diabetes, SGLT2i and DPP-4i have comparable hypoglycemic efficacy, but SGLT2i shows additional advantages in weight loss, reduction in blood pressure, and improvement in renal outcomes. Baseline characteristics of patients may serve as useful references for individualized treatment choices.