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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



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



Diabetes, Obesity and Metabolism



(s)We reviewed randomized controlled trials to compare the efficacy and safety of initial DPP-IV inhibitors and metformin combination therapy with equal-dosage metformin monotherapy in type 2 diabetes. We 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, dipeptidyl peptidase IV inhibitor. Double-blinded RCTs comparing DPP-IV inhibitors initially combined with metformin and metformin monotherapy in non-pregnant drug-na ve adults with type 2 diabetes were included for this study. Extraction of articles was performed by 2 authors using predefined data fields. Meta-analysis was used when studies were homogeneous enough, and datas were shown and not combined if no formal meta-analysis was performed. Five randomized controlled trials met the inclusion criteria. By analysis of different outcomes, patients receiving initial combination of DPP-IV inhibitors and metformin showed a greater reduction in HbA1c from baseline (WMD, -0.55%; 95% CI, -0.63% to -0.46%), a higher rate of achieving target of HbA1c<7% (RR, 1.55; 95%CI,1.43 to 1.67), a significantly lower fasting plasma glucose (FPG) (WMD, -0.97mmol/L, 95% CI, -1.26mmol/L to -0.68mmol/L),while the initial combination therapy and monotherapy did not show a significant difference in incidence of total AEs (51.8% versus 53.7%, respectively; RR, 0.96; 95% CI, 0.91 to 1.02), gastrointestinal AEs (18.2% versus 19.4% respectively; RR, 0.94; 95% CI, 0.82-1.07), drug-related AEs (RR, 0.88; 95% CI, 0.74 to 1.03), and discontinuation due to AEs (RR, 0.85; 95% CI, 0.61 to 1.20). The following outcomes were not included for meta- analysis: change from baseline in postprandial glycemia, beta cell function, insulin sensitivity and body weight as well as incidence of hypoglycemia. The analyses of these trials revealed that the change from baseline of the postprandial glycemia and index of beta-cell function were greater while the risk ratios for incidence of hypoglycemia and body weight increase had no statistical significance. Compared with equal-dosage metformin monotherapy, the initial combination of metformin and DPP-IV inhibitors were more effective in glycemic control without additional risk of adverse events, therefore it can be considered as a beneficial therapeutic regimen for drug-na ve type 2 diabetes patients.

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Accession: 037416979

Download citation: RISBibTeXText

DOI: 10.1111/dom.12193


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