Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

Objective: The influence of dipeptidyl peptidase-4 (DPP4) inhibitors on glycemic variability compared to other oral antidiabetic drugs (OADs), measured based on the mean amplitude of glycemic excursions (MAGE), has not been comprehensively analyzed. The aim of the study was to perform a meta-analysis to compare the effects of DPP4 inhibitors on MAGE with other OADs in type 2 diabetes mellitus (T2DM) patients without concurrent insulin treatments. Methods: The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant randomized controlled trials (RCTs). Study characteristics and outcome data were independently extracted by two authors. A random-effect model was used to combine the results. Results: Fourteen studies with 855 patients were included. Compared to other OADs, DPP4 inhibitors significantly reduced MAGE (mean difference [MD]: -0.69 mmol/L, 95% confidence interval [CI]: -0.95 to -0.43, P < 0.001) with mild heterogeneity (I-2 = 28%). Predefined subgroup analyses suggested that DPP4 inhibitors were more effective in reducing MAGE compared to insulin secretagogues (MD: -0.92 mmol/L, P < 0.001) and non-secretagogues (MD: -0.43 mmol/L, P=0.02), as well as compared to sulfonylureas (MD: -0.91 mmol/L, P < 0.001) and sodium glucose cotransporter 2 inhibitors (MD: -0.67 mmol/L, P=0.03). Conclusions: DPP4 inhibitors may significantly reduce glycemic variability compared to other oral anti-diabetic drugs, as evidenced by MAGE in T2DM patients with no concurrent insulin treatment.Systematic review registrationINPLASY, registration number: INPLASY2021120113.