Aims
To evaluate the association between glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and the risk of bone fracture in patients with type 2 diabetes mellitus (T2DM).
Materials and methods
We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, and Web of Science from inception to 28 February 2018 and identified eligible randomized controlled trials. The following data were extracted from each study: first author, year of publication, sample size, patient characteristics, study design, intervention drug, control drug, follow‐up time, and incident bone fracture events. A meta‐analysis was conducted using Review Manager 5.3 software to calculate the odds ratio (OR) and 95% confidence intervals (CI) for dichotomous variables.
Results
A total of 38 studies with 39 795 patients with T2DM were included. There were 241 incident bone fracture cases (107 in the GLP‐1 RAs group and 134 in the control group). Compared with patients who received placebo and other anti‐diabetic drugs, those who received GLP‐1 RAs treatment showed a pooled OR of 0.71 (95% CI, 0.56‐0.91) for bone fracture. Subgroup analysis showed that treatments with liraglutide and lixisenatide were associated with significantly reduced risk of bone fractures (ORs, 0.56; 95% CI, 0.38‐0.81 and 0.55; 95% CI, 0.31‐0.97, respectively). However, other GLP‐1 RAs did not show superiority to placebo or other anti‐diabetic drugs. Moreover, these beneficial effects were dependent on the duration of GLP‐1 RAs treatment, only a GLP‐1 RAs treatment period of more than 52 weeks could significantly lower the risk of bone fracture in patients with T2DM (OR, 0.71; 95% CI, 0.56‐0.91).
Conclusions
Compared with placebo and other anti‐diabetic drugs, liraglutide and lixisenatide were associated with a significant reduction in the risk of bone fractures, and the beneficial effects were dependent on the duration of treatment.
Introduction: Aggressive medullary thyroid carcinomas (MTC) have a high mortality rate and the treatment for patients diagnosed with advanced MTC is comparatively ineffective. We hence aimed to test the effects of miR-376c-3p on MTC and to explore the relevant mechanism. Material and methods: Cell Counting Kit-8 (CCK-8) and soft agar colony formation assay were applied to evaluate the proliferation of transfected MZ-CRC-1 cells. Wound healing and transwell assay were employed to evaluate MTC cell migration and invasion, respectively. Luciferase assay was performed to validate the downstream target of miR-376c-3p in MZ-CRC-1 cells. Quantitative polymerase chain reaction was used to detect mRNA abundance of key genes. Western blot technique was used to analyze protein levels of HBEGF, E-cadherin, ZO-1, N-cadherin and vimentin. Results: MiR-376c-3p inhibited the viability, migration and invasion of MZ-CRC-1 cells. Moreover, miR-376c-3p mimic downregulated expression of N-cadherin and vimentin but upregulated that of E-cadherin and ZO-1 in MZ-CRC-1 cells. Results for the luciferase reporter assay showed that miR-376c-3p was able to bind the 3′ untranslated region of heparin-binding EGF-like growth factor (HBEGF), of which overexpression nearly nullified the miR-376c-3p mimic-induced inhibitory effects in the MTC cells. Conclusions: MiR-376c-3p showed suppressive effects on MZ-CRC-1 cells via targeting and downregulating HBEGF, suggesting that miR-376c-3p could potentially be targeted for the treatment of MTC.
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