SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a meta-analysis of outcomes

Abstract

Objective To systematically compare sodium-glucose linked transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i) in glycemic control, weight reduction and genital infection risk in type 2 diabetic patients, and provide evidence-based support for individualized clinical medication. Materials and methods A comprehensive search of PubMed, Web of Science, Cochrane Library, and EMBASE was performed for randomized controlled trials (RCTs) from database inception. Data on glycated hemoglobin, body weight, and genital infections were extracted. Risk of bias was assessed with the Cochrane ROB 2.0 tool. Meta-analyses were conducted using RevMan 5.4 and Stata 17.0, with effect sizes pooled by high- and low-dose SGLT2i subgroups. Subgroup analyses, sensitivity analyses, publication bias assessment (funnel plots plus Egger’s test), and GRADE evidence quality rating were performed. Results 10 RCTs were ultimately included. For low-dose SGLT2i, the reduction in glycated hemoglobin was not statistically different from that of DPP4i (mean difference [MD] = 0.01%, 95% confidence interval [CI]: −0.05% to 0.07%, P = 0.75). In contrast, high-dose SGLT2i demonstrated superior glycemic efficacy (MD = −0.15%, 95% CI: −0.27% to −0.03%, P = 0.01). Regardless of dosage, SGLT2i were significantly more effective than DPP4i in reducing body weight (low-dose MD = −1.69, high-dose MD = −1.92; both P < 0.01). Regarding safety, both low- and high-dose SGLT2i were associated with a significantly higher risk of genital infections compared with DPP4i (low-dose odds ratio [OR] = 4.25, high-dose OR = 4.03; both P < 0.01). Subgroup analyses suggested that the glucose-lowering effects might vary among individual SGLT2i agents, but these exploratory findings should be interpreted with caution due to the limited number of studies. Conclusion High-dose SGLT2i offer superior glycemic control versus DPP4i; all SGLT2i doses confer significant weight loss benefits but carry a higher genital infection risk. Clinicians should therefore consider individual glycemic targets, weight status, and infection risk when selecting glucose-lowering therapies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261468619, identifier CRD420261468619.