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PLoS One. 2013 Oct 25;8(10):e76713. doi: 10.1371/journal.pone.0076713. eCollection 2013.

Impact of three oral antidiabetic drugs on markers of β-cell function in patients with type 2 diabetes: a meta-analysis.

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Department of Endocrinology, Changhai hospital, Second Military Medical University, Shanghai, China.



The effect of metformin, pioglitazone and sitagliptin on β-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 β-cell effects of metformin, pioglitazone and sitagliptin.


We searched Pubmed and the Cochrane Center Register of Controlled Trials to identify relevant studies. Trials investigating effects of sitagliptin, metformin or pioglitazone on β-cell function were identified. The primary outcomes were homeostasis model assessment of β-cells (HOMA-β) 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.


Metformin monotherapy was more effective than sitagliptin in improving HOMA-β (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 (-0.137 (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-β and decreasing PI/IR (-0.177 (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).


The included RCTs were of short duration (12-54 weeks). We could not determine long term effects on β-cells.


Metformin improves β-cell function more effectively than pioglitazone or sitagliptin in type 2 diabetes patients. Metformin and sitagliptin improved HOMA-β and PI/IR more than other combinations.

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