Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus

Abstract Aims Dipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM. Methods PubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0. Results Eleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, − 0.70, 95% CI − 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, − 4.50 pg/mL, 95% CI − 4.68 to − 4.32, P