Efficacy and safety of vildagliptin combined with metformin in the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis

Background: Many treatment options are available for type 2 diabetes mellitus (T2DM), but long-term glucose control remains unsatisfactory. Vildagliptin is a highly selective DDP-4 inhibitor, but evidence support its use in combination with metformin is not convincing. Methods: We searched for randomized controlled trials (RCTs) in the Cochrane Library, PubMed, EMBASE, China Knowledge Resource Integrated Database (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Chinese Biomedical Database (CBM). Trial quality was evaluated using the Cochrane Handbook. Primary efficacy measure was reduction in glycated hemoglobin (HbA1c). Safety assessment included hypoglycemic episodes and overall adverse events. Pre-planned subgroup analysis (and comparison) was conducted for trials lasting for <= 52 weeks vs. >52 weeks. Results: The analysis included 12 studies. One study reported the end points at both <= 52 weeks and >52 weeks. In comparison to metformin alone (or metformin plus placebo), the metformin/vildagliptin combination was superior in efficacy measures and comparable in safety profile. A comparison to metformin plus other oral hypoglycemic agents (OHAs) revealed that the metformin/vildagliptin combination is: 1) comparable in terms of HbA1c reduction regardless of follow-up duration; 2) comparable in terms of hypoglycemic episodes and overall adverse events at <= 52 weeks, but superior at >52 weeks. Conclusions: In comparison to metformin plus other OHAs, the metformin/vildagliptin combination is equally effective in HbA1c reduction. The advantage in safety profile of the metformin/vildagliptin combination over metformin plus other OHAs manifests itself upon longer treatment (>52 weeks).