Comparisons Between Dipeptidyl Peptidase-4 Inhibitors And Other Classes Of Hypoglycemic Drugs Using Two Distinct Biomarkers Of Pancreatic Beta-Cell Function: A Meta-Analysis

Background and objectiveDipeptidyl 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-beta). However, whether HOMA-beta 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-beta and proinsulin-to-insulin ratio (PIR).MethodsWe 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 [alpha-glucosidase inhibitors (alpha-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-beta or PIR during study periods were calculated for pairwise comparisons.ResultsThirty-seven and 21 relevant trials were retrieved for comparisons of HOMA-beta and PIR, respectively. HOMA-beta and PIR consistently showed superiority of DPP-4 inhibitors compared with alpha-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-beta showed no significant differences between DPP-4 inhibitors and the two other agents.ConclusionDPP-4 inhibitors appear to be superior to alpha-GIs but inferior to GLP-1 analogues in preservation of beta-cell function assessed by either HOMA-beta 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-beta 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.