The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

The aim of the present meta-analysis was to assess the safety profile of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors in comparison with placebo as add-on to metformin therapy in patients with type 2 diabetes. Randomized controlled trials and controlled clinical trials were identified by searching Pubmed, Embase and the Cochrane Central Register of Controlled Trials database until 15 July 2013. All included studies were critically appraised and analysed with the use of Review Manager 5.1.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement protocol. Twenty randomized and double-blinded studies published in 22 articles fulfilled the inclusion criteria for meta-analysis. The overall results demonstrated that the use of oral antidiabetic agents (analysed separately and together) was not associated with any significantly increased risk of any serious adverse events including hypoglycaemia and gastrointestinal disorders. Moreover, the use of DPP-4 or SGLT-2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin. However, we found that the SGLT-2 inhibitors were more likely to cause a genital infection. Despite some limitations, the findings of this meta-analysis indicate that DPP-4 or SGLT-2 inhibitors have favourable safety profile, and such therapy, when combined with metformin is well tolerated.