A systematic review and meta-analysis of observational studies of the association between the use of incretin-based therapies and the risk of pancreatic cancer.

BACKGROUND: Some early reports in the medical literature have raised concern about a possible increased risk of pancreatic cancer associated with the use of two broad classes of incretin-based therapies, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 receptor agonists. This possibility has been somewhat mitigated by the null findings meta-analyses of randomized controlled trials, but the usefulness of their findings was hampered by serious shortcomings of lack of power and representativeness. These shortcomings can typically be addressed by observational studies, but observational studies on the topic have yielded conflicting findings. A systematic review and meta-analysis of observational studies was performed to qualitatively and quantitatively appraise the totality of evidence on the association between the use of incretin-based therapies and the risk of pancreatic cancer in routine clinical practice. METHODS: The PubMed, Web of Science, Embase, and Google Scholar databases were searched. The study quality was appraised using the ROBINS-I tool and based on the presence of pharmacoepidemiology biases. A random-effects model was used to estimate the summary relative risks with corresponding CIs. RESULTS: A total of 14 studies were included. The qualitative assessment revealed that all studies had inadequate follow-up (≤5 years), 12 studies were suspected to suffer from time-lag bias (due to inappropriate choice of comparator group) to varying extent, five studies included prevalent users, five studies did not implement exposure lag period, five studies had a serious risk of bias due to confounding, and one study had a time-window bias. The quantitative assessment showed no indication of an increased risk when all studies were pooled together (RR 1.04, 95% CI 0.87, 1.24) and when the analysis was restricted to the studies with the least bias (RR 0.77, 95% CI 0.51, 1.17). However, the pooled RRs were more frequently higher in the studies with less rigorous design and analysis. Specifically, a tendency toward an increased risk was observed in the studies with (RR 1.34, 95% CI 1.04, 1.72) or possibly with (RR 1.10, 95% CI 0.89, 1.36) time-lag bias, in the studies that did not apply (RR 1.23, 95% CI 0.93, 1.63) or with potentially inadequate exposure lag period of 6 months (RR 1.13, 95% CI 0.66, 1.94), in the studies that inappropriate comparator group of a combination of unspecified (RR 1.49, 95% CI 1.25, 1.78) or non-insulin (RR 1.15, 95% CI 0.93, 1.42) antidiabetic drugs, and in the studies with serious risk of bias due to confounding (RR 1.18, 95% CI 0.56, 2.49). CONCLUSIONS: In summary, the totality of evidence from observational studies does not support the claim that the use of incretin-based therapies is associated with an increased risk of pancreatic cancer in routine clinical practice. The increased risk of pancreatic cancer observed in observational studies reflects bias resulting from suboptimal methodological approaches, which need to be avoided by future studies.

Serum von Willebrand factor for early diagnosis of lung adenocarcinoma in patients with type 2 diabetes mellitus.

BACKGROUND: The elevation of plasma von Willebrand factor (vWF) has been proposed to be a predictor of lung cancer. Type 2 diabetes mellitus (T2DM) causes endothelial activation, resulting in the secretion of vWF. However, the role of vWF in patients with T2DM complicated with lung cancer remains unclear. AIM: To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ (AIS). METHODS: This study enrolled 43 patients with T2DM combined with lung AIS (T2DM + AIS group), 43 patients with T2DM alone (T2DM group), 43 patients with lung AIS alone (AIS group), and 43 healthy volunteers (control group). The serum levels of vWF, insulin-like growth factor 1, and insulin-like growth factor binding protein 3 were determined. Multiple linear stepwise regression was performed to determine the correlations among variables. RESULTS: Serum concentration of vWF in the T2DM + AIS group was significantly higher than those in the T2DM, AIS, and control groups (P < 0.05). Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group (P < 0.05). There was no significant difference in serum vWF level between the T2DM and AIS groups. In the T2DM + AIS group, serum vWF was independently associated and positively correlated with serum levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 (P < 0.05). CONCLUSION: Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.