Metformin and survival of people with type 2 diabetes and pleural mesothelioma: A population-based retrospective cohort study

Our plain-English summary of Metformin and survival of people with type 2 diabetes and pleural mesothelioma: A population-based retrospective cohort study, by H. Wu, J. Walker, R.A. Damhuis, et al (Lung Cancer, 2016).

The study

• Authors: H. Wu, J. Walker, R.A. Damhuis, D.H. Brewster, S.H. Wild, Scottish Diabetes Research Network Epidemiology Group
• Journal: Lung Cancer
• Published: 2016;99:194-9
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: This study aimed to investigate the effect of metformin on survival of people with type 2 diabetes and pleural mesothelioma.

Materials And Methods: We conducted a retrospective cohort study of people with type 2 diabetes diagnosed with pleural or unspecified mesothelioma between 1993 and 2014 using linked Scottish population-based diabetes and cancer datasets. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards regression models were used to describe the association between use of metformin and all-cause mortality following diagnosis of pleural mesothelioma.

Results: There were 300 people with type 2 diabetes and pleural or unspecified mesothelioma of whom 148 had ever used metformin and 290 died during follow up. The median survival time was 8.8 months and 6.5 months for metformin users and non-users respectively (p=0.37, log-rank test). After adjusting for age, sex, diabetes duration, socio-economic status, and other anti-diabetic medications the hazard ratio for mortality associated with metformin was 0.99 (95% confidence intervals: 0.76-1.28; p=0.92). Similar non-statistically significant associations were obtained in sensitivity analyses based on metformin use in year prior to diagnosis of mesothelioma, use of metformin for more than one year, in people below the mean age at diagnosis of mesothelioma (74 years) and 74 years of age or older, limitation to pleural mesothelioma and following further adjustment for body mass index and smoking.

Conclusion: There was no evidence that metformin improved survival among people with type 2 diabetes and pleural mesothelioma or to support trials of metformin in people with mesothelioma.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In plain English

This retrospective cohort study from Scotland asked whether metformin, a common type 2 diabetes drug, was linked to longer survival in people with type 2 diabetes and pleural or unspecified-site mesothelioma diagnosed from 1993 to 2014. It examined the drug, not asbestos exposure. Linked national diabetes, cancer and death records covered 300 people. Of these, 148 had ever been prescribed metformin before diagnosis, and 290 died during follow-up. Median survival was 8.8 months for metformin users and 6.5 months for non-users, a difference that was not statistically significant. After adjustment for age, sex, diabetes duration, other diabetes drugs and area deprivation, the hazard ratio for death with metformin was 0.99 (95% confidence interval 0.76 to 1.28). Separate analyses gave similar non-significant results. These looked at length of metformin use, age group and pleural cases only, and added adjustment for body mass index and smoking. The authors noted a small sample and no data on tumour stage, other illnesses or cancer treatment. They concluded there was no evidence that metformin improved survival, or to support trials of metformin in mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: population-based retrospective cohort study using linked routine health records
• Who was studied: 300 people in Scotland with type 2 diabetes who were diagnosed with pleural (ICD-10 C45.0) or unspecified-site (C45.9) mesothelioma between 1993 and 2014. Of these, 39 had mesothelioma at unspecified sites. 15 people with peritoneal mesothelioma were excluded because their numbers were small. Mean age at diagnosis was 74 years, and 85.0% were men.
• Exposure: Ever prescription of metformin (and, as other variables, insulin, sulphonylureas and other diabetes drugs) before the mesothelioma diagnosis. Asbestos exposure was not measured or analysed.
• Main results:
  • 148 of the 300 people (49.3%) had ever been prescribed metformin before their mesothelioma diagnosis.
  • 290 patients died during follow-up and 10 were censored (still alive at the end of follow-up). Median follow-up for the whole cohort was 7.5 months.
  • Median survival was 8.8 months (95% CI 7.6 to 10.0) for metformin users and 6.5 months (95% CI 5.3 to 7.7) for non-users. The difference was not statistically significant (log-rank p = 0.37).
  • Without adjustment, the hazard ratio for all-cause death in metformin users compared with non-users was 0.90 (95% CI 0.71 to 1.14; p = 0.37).
  • After adjustment for age, sex, diabetes duration, other anti-diabetic medications and area deprivation (SIMD), the hazard ratio for all-cause death with metformin was 0.99 (95% CI 0.76 to 1.28; p = 0.92).
  • By duration of use, 119 patients had used metformin for more than one year (adjusted HR 1.04, 95% CI 0.79 to 1.37) and 29 for one year or less (adjusted HR 0.86, 95% CI 0.56 to 1.31). Neither was statistically significant.
  • Excluding people with mesothelioma at unspecified sites (pleural cases only), the adjusted hazard ratio was 0.89 (95% CI 0.68 to 1.17; p = 0.41).
  • With further adjustment for BMI or smoking status, among the people who had these data, the hazard ratio was 0.91 (95% CI 0.68 to 1.23; p = 0.55).
  • Older age was a statistically significant predictor of death in the study population, with an adjusted HR of 1.03 (95% CI 1.02 to 1.05) per year of age.
• The authors' conclusion: The authors concluded that there was no evidence that metformin improved survival among people with type 2 diabetes and pleural mesothelioma, and no evidence to support trials of metformin in people with mesothelioma.
• Limitations the authors state:
  • The sample was relatively small, so the estimates were imprecise. According to the authors, metformin could be associated with anything from a 23.6% reduction to a 27.5% increase in the hazard of death.
  • No data were available on mesothelioma stage or histological sub-type.
  • There was no information on comorbidities, glucose control or mesothelioma treatments, so confounding by these factors remains possible.
  • Limited statistical power meant the metformin exposure data could not be stratified further, for example by intensity of use.
  • BMI and smoking were taken from the most recent record before diagnosis, which may not reflect values at the time of diagnosis.
  • The findings may not apply outside Scotland or to people with mesothelioma who do not have diabetes.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cohort Study, Mesothelioma, Median Overall Survival, Hazard Ratio, confidence interval.

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