Efficacy of Various Antidiabetic Agents as Add-On Treatments to Metformin in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

Background and Aim. Diabetes mellitus is a chronic disease that has a great impact on patients and society. Metformin monotherapy is capable of maintaining a target glycemic control only for a short term. The aim of this study was to determine the efficacy of combination therapy of metformin with any antidiabetic agents in type 2 diabetes mellitus (T2DM) patients. Methods. Reports of randomized controlled trials (RCTs) of combination therapy of metformin with various antidiabetic agents in T2DM failing metformin alone were identified. Results. Eight studies were identified in our paper. Thiazolidinediones (TZDs) were as effective as dipeptidyl peptidase IV inhibitors (DPP IV inhs) in reducing HbA1c value (pooled mean difference -0.03%; 95% CI -0.16 to 0.10%). In comparison between TZDs and sulphonylureas (SUs), TZDs reduced fasting plasma insulin (FPI) more effectively than SUs (pool mean difference -5.72 μU/mL; 95% CI -8.21 to -3.22 μU/mL, P < 0.00001), but no significant differences were detected in the effects on HbA1c and fasting plasma glucose (FPG) (pooled mean difference -2.19 mg/dL; 95% CI -11.32 to 6.94 mg/dL, P = 0.64). Conclusions. Our study showed that TZDs reduced FPG better than did DPP IV inhs and decreased FPI more than did SUs.