Systemic Review Of Dipeptidyl Peptidase4Inhibitors’s Effect On Insulin Resistance In Type2Diabetes Mellitus

Background:Type2diabetes mellitus is a chronic and progressive disease characterised by insulin resistance and decreased islet function, and rates of this disease have increased markedly in recent years. Meanwhile some new antidiabetic drugs were presented to us with novel and different mechanisms, including DPP-4inhibitors (Dipeptidyl Peptidase4inhibitors). The DPP-4inhibitor is a kind of incretin enhancer which promotes insulin secretion by inhibiting the activity of DPP-4which is a degrading enzyme of GLP-1and extending the action of this incretin. As a result of its good capacity in lowering blood glucose and improving islet beta cell function with a low incidence of gastrointestinal adverse reaction and no addition of body weight, DPP-4inhibitors have been accept gradually. However, their roles in insulin resistance are still uncertain, and different clinical studies have provided different results.Objective:We conducted this systematic review to compare DPP-4inhibitors with placebo and other oral antidiabetic drugs in aspects of insulin resistance and give a more reasonable answer for clinical use of this kind of drug in patients of insulin resistance.Methods:We searched MEDLINE and EMBASE using the following terms:"controlled clinical trial" and "dipeptidyl peptidase IV inhibitors". Only randomized controlled trials comparing DPP-IV inhibitors with placebo or other oral antidiabetic drugs in non-pregnant drug-naive adults with type2diabetes were included. According to the predefined strategy, we progressed paper screening, data extraction, quality assessment and results combination with tests of heterogeneity and bias.Results:DPP-4inhibitors can significantly improve the level of insulin resistance (HOMA-IR index evaluation) compared with placebo, but the efficacy is weak and the weighted mean difference of change from baseline in HOMA-IR index is-0.109(95%CI;-0.191,-0.027), I2=3.9%. Other indicators of insulin resistance are similar to this result (except Composite ISI), but the application of the OGIS index and the glucose clamp test for evaluating insulin resistance shows more obvious differences. In the clamp test, weighted mean difference (WMD) in M value which stands for insulin resistance was0.789(95%CI;0.503,1.075), I2=0; and in patients with type2diabetes using monotherapy, DPP-4inhibitors improve insulin resistance (change in HOMA-IR index from baseline) more significantly with WMD=-0.193(95%CI,-0.356,-0.030), while the combination treatment the results are not significant:WMD=-0.078(95%CI;-0.188,0.031). In addition, the weighted mean difference of the DPP-4inhibitor compared with metformin in improving insulin resistance (HOMA-IR index change from baseline) is0.398(95%CI;0.194,0.602), I2=0; while1.063(95%CI;0.613,1.514),I2=28.1%with thiazolidinediones;-0.550(95%CI;-0.782,-0.319),I2=0with sulfonylureas; and-0.061(95%CI;-0.242,0.120), I2=3.5%) compared with alpha-glucosidase inhibitors.Conclusions:DPP-4inhibitors can lead to a mild improvement in insulin resistance compared with placebo, but the effect is weaker than that of the traditional insulin sensitizer such as thiazolidinedione and metformin. However, DPP-4inhibitors show obvious advantages over sulfonylureas in this aspect and the advantage over a-glycosidase inhibitors is not significant.