Efficacy and safety of initial combination of DPP-IV inhibitors and metformin versus metformin monotherapy in type 2 diabetes: a systematic review of randomized controlled trials

AimsWe reviewed randomized controlled trials (RCTs) to compare the efficacy and safety of initial dipeptidyl peptidase-IV (DPP-IV) inhibitors and metformin combination therapy with equal-dosage metformin monotherapy in type 2 diabetes. MethodsWe conducted a systematic review of English articles using MEDLINE and EMBASE. Search terms included randomized controlled trial, controlled clinical trial, random allocation, sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin, duotogliptin and dipeptidyl peptidase IV inhibitor. Double-blinded RCTs comparing DPP-IV inhibitors initially combined with metformin and metformin monotherapy in non-pregnant drug-naive adults with type 2 diabetes were included for this study. Extraction of articles was performed by two authors using predefined data fields. Meta-analysis was used when studies were homogeneous enough, and data were shown and not combined if no formal meta-analysis was performed. ResultsFive RCTs met the inclusion criteria. By analysis of different outcomes, patients receiving initial combination of DPP-IV inhibitors and metformin showed a greater reduction in haemoglobinA1c (HbA1c) from baseline [weighted mean difference (WMD), -0.55%; 95% confidence interval (CI), -0.63 to -0.46%], a higher rate of achieving target of HbA1c<7% [risk ratio (RR), 1.55; 95% CI, 1.43-1.67], a significantly lower fasting plasma glucose (FPG) (WMD, -0.97mmol/l; 95% CI, -1.26 to -0.68mmol/l),while the initial combination therapy and monotherapy did not show a significant difference in incidence of total adverse events (AEs, 51.8 vs. 53.7%, respectively; RR, 0.96; 95% CI, 0.91-1.02), gastrointestinal AEs (18.2 vs. 19.4%, respectively; RR, 0.94; 95% CI, 0.82-1.07), drug-related AEs (RR, 0.88; 95% CI, 0.74-1.03) and discontinuation due to AEs (RR, 0.85; 95% CI, 0.61-1.20). The following outcomes were not included for meta-analysis: change from baseline in postprandial glycaemia, -cell function, insulin sensitivity and body weight as well as incidence of hypoglycaemia. The analyses of these trials revealed that the change from baseline of the postprandial glycaemia and index of -cell function were greater while the RRs for incidence of hypoglycaemia and body weight increase had no statistical significance. ConclusionsCompared with equal-dosage metformin monotherapy, the initial combination of metformin and DPP-IV inhibitors were more effective in glycaemic control without additional risk of AEs, therefore it can be considered as a beneficial therapeutic regimen for drug-naive type 2 diabetes patients.