Aims: This meta-analysis was performed to provide an update on the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus (T2DM). Methods:We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words 'alogliptin', 'dutogliptin', 'linagliptin', 'saxagliptin', 'sitagliptin', 'vildagliptin' and 'metformin'. RCTs were selected for meta-analysis if (1) they were RCTs comparing DPP-4 inhibitors plus metformin as initial combination therapy or DPP-4 inhibitor monotherapy to metformin monotherapy, (2) duration of treatment was ≥12 weeks and (3) reported data on haemoglobin A1c (HbA1c) change, fasting plasma glucose (FPG) change, weight change, adverse cardiovascular (CV) events, hypoglycaemia or gastrointestinal adverse events (AEs). Conclusions: DPP-4 inhibitors, which are safe and effective in controlling the blood glucose, may possibly decrease the risk of CV events in patients with T2DM. It could be a credible alternative for T2DM patients who, for some reason, cannot use metformin, or are in high risk of CV exposure. High-quality, large sample and long-term follow-up clinical trails are needed to confirm the long-term conclusions.

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IRX3 genetic variants associate with birth weight, BMI and AST/ALT-related transaminase metabolism, supporting the role of IRX3 as an obesity-associated susceptibility gene.

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