Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1). The present study aimed to evaluate the effect of DPP4i on serum adiponectin in T2DM patients. The PubMed, Embase, and Cochrane library databases were searched from inception to February 2016. Randomized controlled trials, evaluating the DPP4i (sitagliptin and vildagliptin) versus comparator (placebo or active-comparison), in T2DM patients with duration of ≥ 12 weeks, were identified. Weighted differences in means of adiponectin levels were calculated by using a fixed or random-effects model. Ten randomized controlled trials, including 1,495 subjects, were identified. Compared with placebo, DPP4i (sitagliptin and vildagliptin) treatment significantly elevated adiponectin levels by 0.74 μg/mL (95% confidence interval [CI], 0.45 to 1.03) relative to that using an active-comparison by 0.00 μg/mL (95% CI, −0.57 to 0.56). Compared with active-comparison, vildagliptin treatment increased adiponectin levels by 0.32 μg/mL (95% CI, −0.01 to 0.65), whereas sitagliptin treatment decreased adiponectin levels by −0.24 μg/mL (95% CI, −1.07 to 0.58). Trials examining effects of other DPP4i were not found. Sitagliptin and vildagliptin increased serum adiponectin levels and had no stronger effect than traditional oral antidiabetic drugs. Further trials with larger sample size are needed to confirm the results and investigate the association between serum adiponectin levels and treatment of other DPP-4 inhibitors. Registration No in PROSPERO: CRD42016037399 .

Dipeptidyl peptidase-4 inhibitors (DPP-4i) are emerging glucose-lowering agents through interacting with DPP-4 substrate, impact of which on systemic inflammation in type 2 diabetes mellitus (T2DM) remains unknown. This study aimed to evaluate the effect of DPP-4i on modulating serum levels of C-reactive protein (CRP) in T2DM. PubMed, Cochrane library and Embase databases were searched. Randomized controlled trials (RCTs) with comparators were selected. A random-effects model was used for quantitative data analysis. Heterogeneity was evaluated with I2 index. Sensitivity analysis was performed using the one-study remove approach. Sixteen trials with 1607 patients with T2DM were included. Pooled analysis of DPP-4i demonstrated a significant decrease in serum CRP concentrations (− 0.86 mg/L, 95% CI, − 1.36 to − 0.36). No significant difference was found between DPP-4i and active comparators on serum CRP concentrations (0.64 mg/L, 95% CI, − 0.10 to 1.37). Pooled analysis proved to be stable and credible by sensitivity analysis. In subgroup analysis, changes in serum concentrations of CRP were significantly associated with short diabetes duration (− 0.23 mg/L, 95% CI, − 0.41 to − 0.05). DDP-4i effectively reduced serum CRP levels and showed no stronger effect than traditional oral antidiabetic agents. International Prospective Register for Systematic Review (PROSPERO) number: CRD42017076838.

Dipeptidyl peptidase-4 inhibitors (DPP-4i) decrease glucose levels by regulating incretin peptides in type 2 diabetes mellitus (T2DM). This study aimed to determine the modulatory effect of DPP-4i on brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with T2DM. PubMed, Embase and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs) evaluating the impact of DPP-4i on BNP or NT-pro-BNP. A fixed- or random-effects model was used for quantitative analysis, according to the heterogeneity. Sensitivity analysis and publication bias were performed using standard methods. Nine trials with 3056 patients with T2DM were included. Meta-analysis revealed that DPP-4i did not significantly modulate the BNP (0.21 pg/mL, 95% CI − 2.36–2.79) or NT-pro-BNP level (− 7.34 pg/mL, 95% CI − 24.27–9.59). DPP-4i demonstrated no stronger effect on modulating BNP (5.17 pg/mL, 95% CI − 7.48–17.82) or NT-pro-BNP (− 9.95 pg/mL, 95% CI − 44.61–24.71) than active comparators. Pooled analysis was robust and stable after sensitivity analysis. DPP-4i exhibits no significant effect on modulating BNP or NT-pro-BNP and shows no stronger effect than traditional antidiabetic agents in T2DM.

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4i) provide a unique antihyperglycemic effect by regulating incretin peptides in type 2 diabetes mellitus (T2DM) patients who are inadequately controlled with insulin therapy. The aim of this study was to investigate the impact of DPP-4i on leptin concentrations in subjects with T2DM.Methods: Randomized controlled trials (RCTs) with comparators were systematically searched through PubMed, Embase, and the Cochrane Library. Quantitative analysis was performed with a fixed or random-effects model according to heterogeneity. Publication bias was evaluated by using the standard methods for sensitivity analysis.Results: Ten trials with 698 patients with T2DM were included. Pooled analysis demonstrated that DPP-4i did not significantly change leptin concentrations (1.31 ng/mL, 95 % CI − 0.48 to 3.10). DPP-4i exerted effects on modulating leptin levels compared to active comparators (0.21 ng/mL, 95 % CI − 1.37 to 1.78). Meta-analysis was powerful and stable after sensitivity analysis.Conclusions: DPP-4i did not modulate leptin concentrations in T2DM and exerted no stronger effects than traditional antidiabetic agents.