Impact of DPP-4 Inhibitors on Interleukin Levels in Type 2 Diabetes Mellitus.

Objective: Accumulating evidence had implicated pathological involvement of interleukins (ILs) in progression and complications in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl peptidase-4 inhibitors (DPP-4i) produced favorable effects on glucose homeostasis in T2DM. This study aimed to evaluate the impact of DPP-4i on IL concentrations in T2DM.

Methods: PubMed, Embase, and the Cochrane library were systematically searched for relevant articles from inception to May 31, 2024. The search included DPP-4i, T2DM, and randomized controlled trials (RCTs) and related terms. Methods: Placebo- or active agents-controlled human studies were screened. All the RCTs were identified if they provided detailed information on changes of ILs during DPP-4i treatment.

Results: A total of 14 RCTs involving 850 participants were identified. Pooled estimates revealed that DPP-4i significantly lowered IL-6 concentrations (-0.54 pg/mL; 95% CI, -0.82 to -0.25; I2 = 10%, P = .0003) compared to placebo. Similar effects were demonstrated for IL-1β (-16.33 pg/mL; 95% CI, -19.56 to -13.11; I2 = 0%, P < .00001), whereas the effect on IL-18 was not statistically significant (-13.55 pg/mL; 95% CI, -76.95 to 49.85; I2 = 0%, P = .68). Subgroup analysis on IL-6 demonstrated that marked effects were found in groups of basal IL-6 concentrations (< 5 pg/mL), body mass index (≥ 28 kg/m2) and type of DPP-4i (linagliptin).

Conclusions: DPP-4i favorably decreased IL-6 levels in patients with T2DM. The impact of DPP-4i on IL-1β and IL-18 needed to be explored with more studies. Further trials should be performed to elucidate this anti-inflammatory effect of DPP-4i during treatment of T2DM.