Background:An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library.Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies.Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.
Objective: This study was set out to determine whether metformin use influences survival in breast cancer patients treated with antidiabetic drugs as compared to non-users.Research Design and Methods: We used data from the Danish national registries (1996-2008) to identify adult female patients diagnosed with breast cancer who were prescribed antidiabetic medication. We performed multivariate Cox-proportional hazard regression to assess all-cause and breast cancer-specific mortality risks associated with metformin exposure. In a secondary analysis, we stratified use of metformin according to the cumulative number of prescriptions.Results: Of the 1058 breast cancer patients 349 died during follow-up, with breast cancer listed as the primary cause of death for 152 cases. Compared to non-use, current metformin treatment was associated with a significant reduction in overall mortality (adjusted HR 0.74, 95% CI, 0.58-0.96). For breast cancer-specific mortality, a non-significant risk reduction (adjusted HR 0.88, 95% CI, 0.59-1.29) was observed, which became significant after stratification according to cumulative number of prescriptions. An increased risk of both overall and breast cancer-specific mortality was observed in the first 12 months after discontinuation of metformin.Conclusions: We observed a nonsignificant reduction in breast cancer-specific mortality associated with metformin exposure among breast cancer patients treated with antidiabetic drugs. However, our findings suggest that long-term metformin use may have a beneficial effect on survival in patients with breast cancer. Further confirmation of these findings is needed.
Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se.Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines.Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”.Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included.Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment).Limitations: Publication bias seemed to be present. Only published data were used in the analyses.Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.
Cancer patients are vulnerable to complications of respiratory viruses. This systematic review and meta-analysis sought to examine the prevalence of cancer and its association with disease severity in patients with novel coronavirus disease 2019 (COVID-19). Searches were performed in MEDLINE, EMBASE and ScienceDirect from their inception until 28 April 2020. Severe disease was considered to encompass cases resulting in death or as defined by the primary study authors. Meta-analysis was performed using random-effect models. We included 20 studies involving 32,404 patients from China, the United Kingdom,
The need to optimize drug development and facilitate faster access for patients has ignited discussions around the importance of improving interactions between health technology assessment (HTA) bodies and regulatory agencies. In this study, we conducted a systematic review to examine processes, progress, outcomes, and challenges of harmonization/interaction initiatives between HTA bodies and regulatory agencies. MEDLINE, EMBASE, and the International Pharmaceutical Abstracts database were searched up to 21 October 2019. Searches for gray literature (working papers, commissioned reports, policy documents, etc.) were performed via Google scholar and several institutional websites. An online cross-sectional survey was also conducted among HTA (n = 22) and regulatory agencies (n = 6) across Europe to supplement the systematic review. Overall, we found that while there are areas of divergence, there has been progress over time in narrowing the gap in evidentiary requirements for HTA bodies and regulatory agencies. Most regulatory agencies (4/6; 67%) and half (11/22, 50%) of the HTA bodies reported having a formal link for "collaborating" with the other. Several mechanisms such as early tripartite dialogues, parallel submissions (reviews), adaptive licensing pathways, and postauthorization data generation have been explored as avenues for improving collaboration. A number of pilot initiatives have shown positive effects of these models to reduce the time between regulatory and HTA decisions, which may translate into faster access for patients to life-saving therapies. Thus, future approaches aimed at improving harmonization/interaction between HTA bodies and regulatory agencies should build on these existing models/mechanisms while Ofori-Asenso et al. Improving HTA-Regulatory Interactions examining their long-term impacts. Several barriers including legal, organizational, and resource-related factors were also identified, and these need to be addressed to achieve greater alignment in the current regulatory and reimbursement landscape.
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