Impact of Three Oral Antidiabetic Drugs on Markers of β-Cell Function in Patients with Type 2 Diabetes: A Meta-Analysis

Background: The effect of metformin, pioglitazone and sitagliptin on beta-cell function in the treatment of type 2 diabetes is controversial. Therefore, we performed a systematic review and meta-analysis to obtain a better understanding in the beta-cell effects of metformin, pioglitazone and sitagliptin. Methods: We searched Pubmed and the Cochrane Center Register of Controlled Trials to identify relevant studies. Trials investigating effects of sitagliptin, metformin or pioglitazone on beta-cell function were identified. The primary outcomes were homeostasis model assessment of beta-cells (HOMA-beta) and proinsulin/insulin ratio (PI/IR). Secondary outcome was hemoglobin A1c level. We used version 2 of the Comprehensive Meta Analysis software for all statistical analyses. Results: Metformin monotherapy was more effective than sitagliptin in improving HOMA-beta (18.01% (95% CI 11.09% to 24.94%) vs. 11.29% (95% CI 9.21% to 13.37%), P = 0.040) and more effective (-0.13 (95% CI -0.082 to -0.192)) than both sitagliptin (-0.064 (95% CI -0.036 to -0.092), P = 0.019) and pioglitazone (-0.068 (95% CI -0.044 to -0.093), P = 0.015) in decreasing PI/IR. Metformin and sitagliptin combined (40.23% (95% CI 32.30% to 48.16%)) were more effective than sitagliptin and pioglitazone (11.82% (95% CI 6.61% to 17.04%), P = 0.000) and pioglitazone and metformin(9.81% (95% CI 1.67% to 17.95%), P = 0.022) in improving HOMA-beta and decreasing PI/IR (20.177 (95% CI -0.118 to -0.237); -0.080 (95% CI -0.045 to -0.114), P = 0.007; -0.038 (95% CI, -0.005 to 0.071), P = 0.023). Limitations: The included RCTs were of short duration (12-54 weeks). We could not determine long term effects on beta-cells. Conclusions: Metformin improves beta-cell function more effectively than pioglitazone or sitagliptin in type 2 diabetes patients. Metformin and sitagliptin improved HOMA-beta and PI/IR more than other combinations.