Aims: This updated meta-analysis investigates the efficacy and safety of combining sodium-glucose cotransporter 2 inhibitors (SGLT2is) with dipeptidyl peptidase-4 inhibitors (DPP4is) in treating type 2 diabetes (T2D), especially in Asian subpopulations.
Materials and methods: A systematic review was conducted on randomized controlled trials (RCTs) published through January 2024 that compared SGLT2i/DPP4i combination therapy with DPP4i or SGLT2i monotherapy. The primary outcome was haemoglobin A1c (HbA1c) changes. Subgroup analyses were conducted based on the baseline HbA1c level (using 8.0%-8.5% as the cut-off) and racial groups (Asian vs. non-Asian).
Results: This analysis included 17 RCTs with 7588 participants. Compared to DPP4i, the SGLT2i/DPP4i combination significantly reduced HbA1c (mean difference [MD] -0.57%, 95% confidence interval [CI] -0.67 to -0.46%), while promoting modest weight loss (MD -1.57 kg, 95% CI -1.93 to -1.20 kg). When compared to SGLT2i, SGLT2i/DPP4i promoted further reductions in HbA1c (MD -0.46%, 95% CI -0.55 to -0.38%) with no significant effects on body weight. Subgroup analyses revealed that the efficacy of adding DPP4i in reducing HbA1c was more pronounced in Asian participants (MD -0.55%, 95% CI -0.71 to -0.39) than in non-Asian participants (MD -0.38%, 95% CI -0.46 to -0.31). The combination therapy was associated with a similar risk of hypoglycaemia compared to both monotherapy groups, with no statistically significant differences observed.
Conclusions: Combination therapy of SGLT2i and DPP4i improves glycaemic control in T2D, with enhanced DPP4i efficacy noted in Asian populations, highlighting its role in personalized diabetes management for these patients.
Keywords: DPP4 inhibitor; SGLT‐2 inhibitors; meta‐analysis; type 2 diabetes.
© 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.