Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison

Paul Craddy, Hannah-Jayne Palin, K Ian Johnson, Paul Craddy, Hannah-Jayne Palin, K Ian Johnson

Abstract

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 (HbA1c) or body weight, or the proportions of patients achieving HbA1c <7% or experiencing a hypoglycemic event, apart from in patients on alogliptin plus metformin, who achieved HbA1c <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.

Figures

Fig. 1
Fig. 1
Number of articles proceeding at each stage of the systematic review. †Articles excluded for more than one reason. ‡Number of RCTs does not add up to 83 as each RCT could be used in multiple sets of analyses. DPP-4 dipeptidylpeptidase-4 inhibitor, RCT randomized controlled trial, SU sulfonylurea
Fig. 2
Fig. 2
Networks of eligible comparisons for HbA1c mean change from baseline for a DPP-4 monotherapy, b DPP-4 plus metformin, c DPP-4 plus SU, d DPP-4 plus metformin plus SU, e DPP-4 plus pioglitazone, and f DPP-4 plus insulin. The width of the lines is proportional to the number of trials comparing each pair of treatments, and the size of each node is proportional to the number of trials for each treatment. DPP-4 dipeptidylpeptidase-4 inhibitor, HbA1c glycosylated hemoglobin, SU sulfonylurea

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Source: PubMed

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