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

Jin Lu,Huihua Li,Jiajie Zang,Bridget Wagner

doi:10.1371/journal.pone.0076713

Abstract

BackgroundThe 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.MethodsWe 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.ResultsMetformin 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).LimitationsThe included RCTs were of short duration (12–54 weeks). We could not determine long term effects on β-cells.ConclusionsMetformin 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.

Highlights

Progressive b-cell dysfunction and failure are fundamental pathogenic consequences of type 2 diabetes
Metformin monotherapy was more effective than sitagliptin in improving homeostasis model assessment of bcells (HOMA-b) (18.01% vs. 11.29%, P = 0.040) and more effective (20.137) than both sitagliptin (20.064, P = 0.019) and pioglitazone (20.068, P = 0.015) in decreasing proinsulin/ insulin ratio (PI/IR)
Metformin and sitagliptin combined (40.23% (95%confidence intervals (CIs) 32.30% to 48.16%)) were more effective than sitagliptin and pioglitazone (11.82%, P = 0.000) and pioglitazone and metformin(9.81%, P = 0.022) in improving HOMA-b and decreasing PI/IR (20.177; 20.080, P = 0.007; 20.038, P = 0.023)

Summary

Introduction

Progressive b-cell dysfunction and failure are fundamental pathogenic consequences of type 2 diabetes. Assessment of b-cell function may be helpful in selecting the most appropriate therapy Both b-cell function, via the homeostasis model assessment of bcells (HOMA-b) [1], and b-cell dysfunction, via the proinsulin/ insulin ratio (PI/IR), can be measured in type 2 diabetes [2]. Increases in HOMA-b indicate preservation of b-cell function, whereas decreases in PI/IR driven by proinsulin indicate improvement in the secretory and, possibly, resistance profile of b-cells [3,4]. Worsening of these surrogate measures may be correlated with b-cell failure. We performed a systematic review and meta-analysis to obtain a better understanding in the b-cell effects of metformin, pioglitazone and sitagliptin

Methods

Results

Conclusion