Efficacy and Safety of Triple Therapy with SGLT-2 Inhibitor, DPP-4 Inhibitor, and Metformin in Type 2 Diabetes: A Meta-Analysis.

Objective: Type 2 diabetes poses significant pain, economic burden, and health risks. This meta-analysis evaluates the efficacy and safety of triple therapy with SGLT-2 inhibitor add-on to DPP-4 inhibitor plus metformin for type 2 diabetes treatment. Methods: A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of triple therapy (SGLT-2 inhibitor + DPP-4 inhibitor + metformin) compared to dual therapy (DPP-4 inhibitor + metformin) in type 2 diabetes. The search covered the period from inception to December 2018. Two reviewers independently screened the literature, extracted data, and assessed study quality. Meta-analysis was performed using RevMan 5.3 software. Results: A total of eight randomized controlled trials were included in this meta-analysis. The results showed that compared to dual therapy with DPP-4 inhibitor add-on to metformin, triple therapy with SGLT-2 inhibitor add-on to DPP-4 inhibitor plus metformin was associated with greater reductions in HbA1c, fasting blood glucose, postprandial blood glucose, body weight, and blood pressure (P < .05). However, the risk of genital tract infection was higher in the triple therapy group (OR = 4.43, 95% CI (2.26, 8.70), P < .0001), while there were no statistically significant differences in the incidence of adverse events, hypoglycemia episodes, urinary tract infection, and fractures between the two groups (P > .05). Conclusions: Based on current evidence, triple therapy was found to significantly improve blood glucose, body weight, and blood pressure when compared to dual therapy. Safety indicators did not show significant differences, except for an increased risk of genital tract infection.