ArticleEpidemiology (Cambridge, Mass.)2023
Evaluating Metformin Strategies for Cancer Prevention: A Target Trial Emulation Using Electronic Health Records.
Article in Epidemiology (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Association Between Metformin Use and Risk of Lung Cancer in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.Cancer reports (Hoboken, N.J.) · 2026 · on this mapPooled it
- Review
- Effectiveness of Metformin in Preventing Colorectal Cancer Among Japanese Patients With Type 2 Diabetes: A Target Trial Emulation.Pharmacoepidemiology and drug safety · 2026Article
- Evaluating the Impact of Putative Metformin Targets on Cancer Outcomes: A Drug-Target Mendelian Randomization Study.Diabetes, obesity & metabolism · 2026Article
- Effect of Metformin on the Risk of Post-COVID-19 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- The Ideal Trial: Defining Causal Estimands that Balance Relevance and Feasibility in Target Trial Emulations and Actual Randomized Trials.Epidemiology (Cambridge, Mass.) · 2026Review
- Design and Implementation of Observational Studies Emulating a Target Trial.JAMA network open · 2026Article
- Pharmacological mechanisms and clinical impacts of antidiabetic drugs on colorectal cancer risk: a systematic review.Frontiers in pharmacology · 2026Review
- Risk of major adverse cardiovascular events with aripiprazole versus olanzapine, quetiapine, and risperidone in severe mental illness: a target trial emulation.Nature communications · 2025Article
- Article
- Emerging uncertainty on the anti-aging potential of metformin.Ageing research reviews · 2025Review
- Repurposing Metformin in Precision Oncology: Mechanistic Insights, Biomarker-Guided Strategies, and Translational Imperatives.Medicina (Kaunas, Lithuania) · 2025Review
- Article
- Peri-operative anti-inflammatory drug use and seizure recurrence after resective epilepsy surgery: Target trials emulation.iScience · 2025Article
- Effect of leukotriene receptor antagonist use on the future risk of Parkinson's disease in older patients with asthma.Brain communications · 2025Article
- A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.Cancers · 2024Review
- Why is target trial emulation not being used in health technology assessment real-world data submissions?Journal of comparative effectiveness research · 2024Article
- Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.International journal of cancer · 2024Article
- Does metformin really reduce prostate cancer risk: an up-to-date comprehensive genome-wide analysis.Diabetology & metabolic syndrome · 2024Article
- Patients with oral tongue squamous cell carcinoma and co‑existing diabetes exhibit lower recurrence rates and improved survival: Implications for treatment.Oncology letters · 2024Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMetformin users appear to have a substantially lower risk of cancer than nonusers in many observational studies. These inverse associations may be explained by common flaws in observational analyses that can be avoided by explicitly emulating a target trial.
methodsWe emulated target trials of metformin therapy and cancer risk using population-based linked electronic health records from the UK (2009-2016). We included individuals with diabetes, no history of cancer, no recent prescription for metformin or other glucose-lowering medication, and hemoglobin A1c (HbA1c) <64 mmol/mol (<8.0%). Outcomes included total cancer and 4 site-specific cancers (breast, colorectal, lung, and prostate). We estimated risks using pooled logistic regression with adjustment for risk factors via inverse-probability weighting. We emulated a second target trial among individuals regardless of diabetes status. We compared our estimates with those obtained using previously applied analytic approaches.
resultsAmong individuals with diabetes, the estimated 6-year risk differences (metformin - no metformin) were -0.2% (95% CI = -1.6%, 1.3%) in the intention-to-treat analysis and 0.0% (95% CI = -2.1%, 2.3%) in the per-protocol analysis. The corresponding estimates for all site-specific cancers were close to zero. Among individuals regardless of diabetes status, these estimates were also close to zero and more precise. By contrast, previous analytic approaches yielded estimates that appeared strongly protective.
conclusionsOur findings are consistent with the hypothesis that metformin therapy does not meaningfully influence cancer incidence. The findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.