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Effect of dipeptidyl-peptidase-4 inhibitors on C-reactive protein in patients with type 2 diabetes: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSIONS: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.

SUBMITTER: Liu X

PROVIDER: S-EPMC6580696 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Effect of dipeptidyl-peptidase-4 inhibitors on C-reactive protein in patients with type 2 diabetes: a systematic review and meta-analysis.

Liu Xin X Men Peng P Wang Bo B Cai Gaojun G Zhao Zhigang Z

Lipids in health and disease 20190618 1

<h4>Background</h4>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.<h4>Methods</h4>PubMed, Cochrane library and Embase databases were searched. Randomized controlled trials (RCTs) with comparators were selected. A random ...[more]

PMID: 31208420

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Project description:Aims Hyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM. Materials and methods Randomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUCglucagon) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies. Results A total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, P<0.001; I2 = 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all P for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, P<0.001; I2 = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues (P for subgroup difference =0.03). Systematic review registration https://inplasy.com/, identifier INPLASY202280104. Conclusions DPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.

Project description:To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes.Systematic review and meta-analysis of randomised and observational studies.Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts.Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure.Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach.Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use.The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use.

Project description:ObjectiveTo examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases.DesignSystematic review and pairwise and network meta-analysis.Data sourcesPubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021.Eligibility criteriaRandomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs.Main outcome measuresComposite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases.Data extraction and data synthesisTwo reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals.ResultsA total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43); risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79); risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists.ConclusionsDipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice.Systematic review registrationPROSPERO CRD42021271647.

Dataset Information

Effect of dipeptidyl-peptidase-4 inhibitors on C-reactive protein in patients with type 2 diabetes: a systematic review and meta-analysis.

Publications

Effect of dipeptidyl-peptidase-4 inhibitors on C-reactive protein in patients with type 2 diabetes: a systematic review and meta-analysis.

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