Introduction:

This study aimed to assess the efficacy, safety, and tolerability of combination therapy with SGLT2 inhibitors (SGLT2i) and DPP-4 inhibitors (DPP-4i) vs placebo as initial or add-on therapy in Asian patients with type 2 diabetes mellitus (T2DM), considering there is heterogeneity in available regional data.

Methods:

• Databases Searched: MEDLINE, Embase, Cochrane (up to August 2023)
• Inclusion: Trials assessing safety and efficacy of SGLT2i + DPP-4i combination (± metformin) in Asian individuals
• Outcomes:
  1. Glycemic: Mean change in HbA1c
  2. Extra-glycemic: Mean change in body weight and systolic blood pressure (SBP), and hypoglycemia risk at least for 24 weeks
• Statistical Analysis: Meta-analysis using CMA v4 software; standardized mean differences (SMDs) and confidence intervals (CIs) were reported

Results:

1. Studies Included: 9 RCTs; N = 2,170 patients
   1. 3 as initial combination therapy
   2. 3 of SGLT2i added to DPP-4i
   3. 3 of DPP-4i added to SGLT2i
2. HbA1c Reduction:
   1. Vs. DPP-4i: −0.95% (95% CI: −1.09, −0.81)
   2. Vs. SGLT2i: −0.97% (95% CI: −1.11, −0.83)
3. Other Benefits:
   1. Favorable effects on weight and SBP vs. DPP-4i monotherapy
   2. No difference in individuals on SGLT2i alone
4. Safety: No significant difference in adverse events across groups

Conclusion:

Combination of SGLT2i and DPP-4i in Asian patients with T2DM showed significant glycemic improvement in Asian population. Safety was comparable across arms. Further high-quality studies are needed to confirm these findings.

ADA 2025, 20-23 June, Chicago