Effects of Incretin - based Therapy on High - sensitivity C - reactive Protein in Patients with Type 2 Diabetes: A Systematic Review and Meta - Analysis

ABSTRACT Background: Recently, studies had shown that incretin-based therapies could reduce the levels of pro-inflammatory markers. The data on the effects of incretin-based therapies on serum high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetes (T2DM) were inconsistent. Objective: The objective of the study was to assess the effects of incretin-based therapies on hs-CRP in patients with T2DM by meta-analysis. Methods: We searched PubMed, EMBASE, the Cochrane Collaboration Library, and Web of Science to identify the eligible randomized clinical trials until August 2019. The pooled standard mean differences (SMD) were calculated by random-effects model using STATA 11.0. Results: Twenty-five studies with 28 randomized controlled trials were finally included into the meta-analysis. Meta-analysis revealed a significant reduction in hs-CRP following treatment with incretin-based regimens compared to controls (SMD = −0.452, p < 0.001). Subgroup analysis of different class of incretin-based drugs showed that therapy with both dipeptidyl peptidase 4 inhibitors (DPP-4Is, SMD = −0.338, p = 0.026) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs, SMD = −0.544, p = 0.003) caused significant reductions in hs-CRP. Besides, there was a significant reduction in hs-CRP with an intervention duration more than 24 weeks (SMD = −0.465, p = 0.001), while no significant difference with <24 weeks. Meta-regression analyses showed that better glycemic control and more body mass index (BMI) decline were associated with hs-CRP reduction after incretin-based therapies. Conclusions: This meta-analysis suggests that incretin-based therapies, both GLP-1 RAs and DPP-4Is, can cause a significant reduction in hs-CRP in patients with T2DM, which is related to long intervention duration, better glycemic control, and more BMI decline.

Expression of Glucagon-Like Peptide-1 Receptor in Papillary Thyroid Carcinoma and Its Clinicopathologic Significance

BACKGROUND: Incretin-based therapies are rapidly becoming one of the main glycemic control strategies in diabetes. Considering the large numbers of papillary thyroid carcinomas (PTCs) and possible effects of glucagon-like peptide-1 (GLP-1) on cell proliferation, the expression of GLP-1 receptor (GLP-1R) in PTC is likely to have clinical significance. We performed this study to evaluate the expression of GLP-1R in PTC and the clinical meaning of GLP-1R expression in PTC. METHODS: Fifty-six cases of PTC, four cases of medullary thyroid cancer (MTC), seven cases of nodular hyperplasia and 56 normal thyroid tissue samples were selected for immunostaining for GLP-1R. Clinical parameters were obtained by retrospective review of medical records. RESULTS: Immunohistochemical staining for GLP-1R showed immunoreactivity in 18 of 56 cases of PTC (32.1%). All four cases of MTC exhibited cytoplasmic GLP-1R expression. Nodular hyperplasia exhibited immunoreactivity in two of seven cases (28.6%). All normal thyroid follicular cells showed negative immunoreactivity. In univariable and multivariable analyses, tumor multifocality was negatively correlated with GLP-1R expression. Extrathyroidal extension showed positive association with GLP-1R expression that was almost significant. Sex, age, tumor size, and lymph node metastasis were not significantly associated with GLP-1R expression. CONCLUSION: Some parts of PTC tissues express GLP-1R, and GLP-1R expression in PTC was negatively correlated with tumor multifocality. The long-term influence of pharmacologically increased GLP-1 on thyroid follicular cells and development and progression of tumors originating from thyroid follicular cells should be investigated.

A meta-analysis of GI adverse events of GLP-1 receptor agonists and DPP-4 inhibitors / 中国药学杂志

OBJECTIVE: To compare the gastrointestional (GI) adverse events of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors by systematic review and meta-analysis to provide reference for clinicians. METHODS: The following databases were searched: Pubmed, Embase, Cochrane, ClinicalTrials, and CNKI. And the following terms were used to search head to head studies comparing the GI adverse events of GLP-1 receptor agonists and DPP-4 inhibitors: "GLP-1 receptor agonist", "DPP-4 inhibitor", "incretin-based therapy", "adverse events", and "safety". Meta-analysis was performed by Revman 5.0 software, with results expressed as odds ratio (OR) and 95% confidence interval (CI) for GI adverse events. RESULTS: A total of 1 231 articles were obtained, among which six randomized clinical trials (RCTs) which include 884 GLP-1 receptor agonists users and 798 DPP-4 inhibitors users (total number=1 682), were included for the meta-analysis. The result showed that GLP-1 receptor agonists were associated with a higher incidence of GI adverse events, the ORs of high dose GLP-1 receptor agonists versus DPP-4 inhibitors for nausea, vomiting, diarrhea, and constipation were 4.68(3.36, 6.52), 4.66(2.51, 8.65), 2.17(1.54, 3.06) and 2.39(1.35, 4.24), respectively; the ORs of low dose GLP-1 receptor agonists versus DPP-4 inhibitors for nausea, vomiting, diarrhea, and constipation were 4.09(3.06, 5.48), 3.80(2.22, 6.50), 2.06(1.46, 2.93) and 2.39(1.35, 4.24), respectively. CONCLUSION: Compared to DPP-4 inhibitors, GLP-1 receptor agonists are associated with a higher incidence of GI side effects including nausea, vomiting, diarrhea, and constipation.

Effect of Sitagliptin in Type 1 or Type 2 Diabetic Patients with Absolute Insulin Deficiency: A 48 Weeks Observational Study.

Aims: The aim of this study is to investigate the long-term efficacy of sitagliptin added to insulin in type 1 or type 2 diabetic patients with absolute insulin deficiency. Study Design: 48 weeks open-label, observational study. Place and Duration of Study: Department of Internal Medicine, Gyoda General Hospital, between June 2010 and December 2012. Methodology: Sitagliptin 25-100 mg/day was added to the ongoing insulin therapy in those without any detectable post-meal C-peptide levels. HbA1c and other parameters were followed for 48 weeks. Results: Effective reductions of HbA1c levels were already observed at 12 weeks and sustainable throughout the study period. However, 2 subjects had severe hypoglycemic evens. Post-meal C-peptide remained undetectable with all the subjects. Interestingly, significant increases of body weight were observed. Conclusion: Sitagliptin as an adjunct to insulin in patients with absolute insulin deficiency may be effective and sustainable for at least 48 weeks, allowing for less intense therapy. However, it should be noted that some patients may have severe hypoglycemic events. In spite of the significant glycemic effects of sitagliptin in the setting of this study, endogenous insulin secretory capacity remained absent, suggesting that the glucose lowering effect of this drug may be mediated through GLP-1 independent pathway as well.