Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Online Letters: Comments and Responses

Comment on: Suissa and Azoulay. Metformin and the Risk of Cancer: Time-Related Biases in Observational Studies. Diabetes Care 2012;35:2665–2673

  1. Michael Bodmer, MD, MSC1,2⇑,
  2. Susan S. Jick, DSC3 and
  3. Christoph R. Meier, PHD2,3,4
  1. 1Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
  2. 2Emergency Department, Kantonsspital Bruderholz, Bruderholz, Switzerland
  3. 3Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts
  4. 4Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
  1. Corresponding author: Michael Bodmer, bodmerm{at}uhbs.ch.
Diabetes Care 2013 Jun; 36(6): e85-e85. https://doi.org/10.2337/dc12-2693
PreviousNext
  • Article
  • Info & Metrics
  • PDF
Loading

We agree with Suissa and Azoulay (1) that observational studies, particularly those of drug effects, can be subject to biases and that “time-related” biases must be carefully controlled in these types of studies. In their recently published article (1), Suissa and Azoulay have attempted to “show that several of the observational studies investigating the association between metformin and cancer incidence and mortality are affected by these time-related biases.” Since several of our studies have been so charged, we have carefully considered their concerns in relation to our own research (2–5).

In their article, Suissa and Azoulay criticized four of our studies (three case-control [2–4] and one nested case-control [5]; by the way, they are not all nested as claimed). Their concerns about our articles were restricted to “time window bias,” known to others as bias due to differential exposure opportunity, which is an important potential bias that indeed should be controlled for. In our studies we either matched on length of time in the database (2–4), or we carefully assessed the comparability of exposure opportunity between cases and controls (5). In fact, in the breast cancer study we did adjust for length of time in the database, which we reported to be similar between cases and controls. Thus, there is no reason to suspect that controls would have had longer records than cases, possibly accounting for the decreased risk associated with long-term exposure to metformin observed in our study. There were, however, cases and controls in that study with long-term exposure to various other oral hypoglycemic drugs that were not associated with the risk of breast cancer. It seems implausible that the exposure opportunity was equal between cases and controls for all other hypoglycemic drugs while it differed only for patients with long-term use of metformin, the group of patients yielding the only decreased relative risk estimate in our analysis. Thus we believe that there was no evidence for exposure opportunity bias in our study, and the speculation by Suissa and Azoulay about what in theory may or may not have happened is not founded.

There are particular methodological concerns in studies of drugs in relation to diabetes where published guidelines prescribe a stepwise treatment approach usually starting with metformin. In such studies, matching cases and controls on length of diabetes history invariably matches on duration of diabetes treatment, which will bias the observed measure of association toward no effect. Suissa and Azoulay commented on selected results from our studies without providing scientific evidence for a significant role of differential exposure opportunity bias. Furthermore, they ignored (null) results from the same studies that did not fit their assertion, raising the question of whether their choice of articles and findings to review was perhaps subject to its own bias.

Acknowledgments

No potential conflicts of interest relevant to this article were reported.

  • © 2013 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

References

  1. ↵
    1. Suissa S,
    2. Azoulay L
    . Metformin and the risk of cancer: time-related biases in observational studies. Diabetes Care 2012;35:2665–2673
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Bodmer M,
    2. Becker C,
    3. Meier C,
    4. Jick SS,
    5. Meier CR
    . Use of metformin and the risk of ovarian cancer: a case-control analysis. Gynecol Oncol 2011;123:200–204
    OpenUrlCrossRefPubMed
    1. Bodmer M,
    2. Becker C,
    3. Meier C,
    4. Jick SS,
    5. Meier CR
    . Use of metformin is not associated with a decreased risk of colorectal cancer: a case-control analysis. Cancer Epidemiol Biomarkers Prev 2012;21:280–286
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Bodmer M,
    2. Becker C,
    3. Meier C,
    4. Jick SS,
    5. Meier CR
    . Use of antidiabetic agents and the risk of pancreatic cancer: a case-control analysis. Am J Gastroenterol 2012;107:620–626
    OpenUrlCrossRefPubMed
  4. ↵
    1. Bodmer M,
    2. Meier C,
    3. Krähenbühl S,
    4. Jick SS,
    5. Meier CR
    . Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 2010;33:1304–1308
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Diabetes Care: 36 (6)

In this Issue

June 2013, 36(6)
  • Table of Contents
  • About the Cover
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Comment on: Suissa and Azoulay. Metformin and the Risk of Cancer: Time-Related Biases in Observational Studies. Diabetes Care 2012;35:2665–2673
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Comment on: Suissa and Azoulay. Metformin and the Risk of Cancer: Time-Related Biases in Observational Studies. Diabetes Care 2012;35:2665–2673
Michael Bodmer, Susan S. Jick, Christoph R. Meier
Diabetes Care Jun 2013, 36 (6) e85; DOI: 10.2337/dc12-2693

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Comment on: Suissa and Azoulay. Metformin and the Risk of Cancer: Time-Related Biases in Observational Studies. Diabetes Care 2012;35:2665–2673
Michael Bodmer, Susan S. Jick, Christoph R. Meier
Diabetes Care Jun 2013, 36 (6) e85; DOI: 10.2337/dc12-2693
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Acknowledgments
    • References
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Comment on Khunti et al. Clinical Inertia in People With Type 2 Diabetes: A Retrospective Cohort Study of More Than 80,000 People. Diabetes Care 2013;36:3411–3417
  • Response to Comment on Khunti et al. Clinical Inertia in People With Type 2 Diabetes: A Retrospective Cohort Study of More Than 80,000 People. Diabetes Care 2013;36:3411–3417
  • Comment on Lázaro-Martínez et al. Antibiotics Versus Conservative Surgery for Treating Diabetic Foot Osteomyelitis: A Randomized Comparative Trial. Diabetes Care 2014;37:789–795
Show more Online Letters: Comments and Responses

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.