To provide genetic validation for repositioning of metformin in cancer prevention, we assessed genetically proxied effects of putative metformin targets on cancer outcomes using a drug-target Mendelian randomization (MR) design.<h4>Materials and methods</h4>We identified genetic proxies of 11 metformin targets (PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, ETFDH, GPD1, SLC47A1 and ACACB) based on their associations with tissue-specific gene expression, overall/sex-specific HbA1c and type 2 diabetes. This evidence concerns the gene ETFDH and cancer.