Evaluating the Impact of Putative Metformin Targets on Cancer Outcomes: A Drug‐Target Mendelian Randomization Study
Authors' conclusion
Metformin may prevent colorectal cancer via the AMPKγ1 (PRKAG1) target based on genetic evidence, supporting the evaluation of metformin use in colorectal cancer prevention using randomised controlled trials.
Study context
- Population
- Genetic proxies of 11 metformin targets based on associations with tissue-specific gene expression, overall/sex-specific HbA1c and T2D; five major cancers
- Comparison
- Genetically proxied putative metformin targets vs cancer outcomes
- Outcome
- Cancer risk (five major cancers)
Methodological detailsconventional Mendelian randomization (MR) of HbA1c with cancer (inverse variance method), sensitivity analyses, false discovery rate correction for multiple comparisons
- Conventional MR of HbA1c with cancer (inverse variance method)
- Sensitivity analyses
- False discovery rate correction for multiple comparisons
Main finding
As reported in the abstract
PRKAG1: colorectal cancer, OR per mmol/mol reduction in overall HbA1c (95% CI 0.63-0.87; p = 0.001); consistent in sex-specific analysis
0.74
GPD1: no significant association, OR
1.00
95% CI 0.74–1.36p = 0.98
Further findings
Conventional MR: HbA1c and cancer
- OR per mmol/mol (95% CI 0.99-1.02); PRKAG1 effect unlikely mediated by HbA1c reduction
- 1.01
Original publication
Evaluating the Impact of Putative Metformin Targets on Cancer Outcomes: A Drug‐Target Mendelian Randomization Study. Diabetes Obes Metab. Published 27 February 2026. doi:10.
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