Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison

Objective: To compare the safety and efficacy of the dipeptidylpeptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes and inadequate glycemic control. Design: Systematic review of randomized controlled trials (RCTs), health economic evaluation studies, systematic reviews, and meta-analyses, followed by primary Bayesian mixed treatment comparison meta-analyses (MTCs), and secondary frequentist direct-comparison meta-analyses using a random-effects model. Outcomes were reported as weighted mean change from baseline, or odds ratio (OR) with 95% credible interval. Data sources: MEDLINE, MEDLINE In-Process, EMBASE, and BIOSIS via Dialog ProQuest; Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews via EBSCO; four diabetes and two technical congress abstracts; and health technology assessment organization websites. Eligibility criteria: Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment. Data extraction and analysis: Title/abstracts were reviewed for eligibility, followed by full-text review of publications remaining after first pass. A three-person team filtered articles and an independent reviewer checked a random selection (10%) of filtered articles. Data extraction and quality assessment of studies were also independently reviewed. Five DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin) were compared via meta-analysis (where data were available) as monotherapy, dual therapy (plus metformin, sulfonylurea, pioglitazone, or insulin), and triple therapy (plus metformin/sulfonylurea). Results: The review identified 6,601 articles; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis. MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin (HbA(1c)) or body weight, or the proportions of patients achieving HbA(1c) <7% or experiencing a hypoglycemic event, apart from in patients on alogliptin plus metformin, who achieved HbA(1c) <7% more frequently than those treated with saxagliptin plus metformin [OR 6.41 (95% CI 3.15-11.98) versus 2.17 (95% CI 1.56-2.95)]. Conclusions: This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes, either as monotherapy or combination therapy.