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Comparisons between dipeptidyl peptidase-4 inhibitors and other classes of hypoglycemic drugs using two distinct biomarkers of pancreatic beta-cell function: A meta-analysis

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  • Masahiro Takahashi
  • Misa Shibasaki
  • Hirotoshi Echizen
  • Akifumi Kushiyama

Abstract

Background and objective: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been suggested to have pancreatic beta-cell preserving effect according to studies using homeostatic model of assessment for beta-cell function (HOMA-β). However, whether HOMA-β is a suitable biomarker for comparisons between hypoglycemic drugs with different mechanisms of action remains unclear. Therefore, we conducted a meta-analysis to compare the effects of DPP-4 inhibitors and other classes of hypoglycemic drugs on HOMA-β and proinsulin-to-insulin ratio (PIR). Methods: We searched MEDLINE, CENTRAL, and Ichushi-web for the period of 1966 to May 2020. We collected randomized, controlled clinical trials in patients with type 2 diabetes mellitus comparing DPP-4 inhibitors and other classes of hypoglycemic agents [α-glucosidase inhibitors (α-GIs), glucagon-like peptide-1 (GLP-1) analogues, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, or thiazolidinediones]. Weighted mean differences and 95% confidence intervals of changes in HOMA-β or PIR during study periods were calculated for pairwise comparisons. Results: Thirty-seven and 21 relevant trials were retrieved for comparisons of HOMA-β and PIR, respectively. HOMA-β and PIR consistently showed superiority of DPP-4 inhibitors compared with α-GIs. Both biomarkers consistently supported inferiority of DPP-4 inhibitors compared with GLP-1 analogues. However, PIR showed inferiority of DPP-4 inhibitors compared with metformin, and superiority compared with SGLT2 inhibitors, whereas HOMA-β showed no significant differences between DPP-4 inhibitors and the two other agents. Conclusion: DPP-4 inhibitors appear to be superior to α-GIs but inferior to GLP-1 analogues in preservation of beta-cell function assessed by either HOMA-β or PIR. DPP-4 inhibitors seem to be superior to SGLT2 inhibitors but inferior to metformin on islet function assessed only by PIR. Because HOMA-β and PIR may indicate different aspects of beta-cell function, results of beta-cell function preserving effects of hypoglycemic agents should be interpreted with caution.

Suggested Citation

  • Masahiro Takahashi & Misa Shibasaki & Hirotoshi Echizen & Akifumi Kushiyama, 2020. "Comparisons between dipeptidyl peptidase-4 inhibitors and other classes of hypoglycemic drugs using two distinct biomarkers of pancreatic beta-cell function: A meta-analysis," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-20, July.
    • Handle: RePEc:plo:pone00:0236603
    DOI: 10.1371/journal.pone.0236603
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    References listed on IDEAS

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    1. Jin Lu & Jiajie Zang & Huihua Li, 2013. "Impact of Three Oral Antidiabetic Drugs on Markers of β-Cell Function in Patients with Type 2 Diabetes: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-9, October.
    2. Alessandro Liberati & Douglas G Altman & Jennifer Tetzlaff & Cynthia Mulrow & Peter C Gøtzsche & John P A Ioannidis & Mike Clarke & P J Devereaux & Jos Kleijnen & David Moher, 2009. "The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-28, July.
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