In the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) and EMPA-REG OUTCOME trials, despite enrolled individuals being at very high risk of micro- and macrovascular complications, around 25% of participants were not treated with statins, around 20% were not receiving renin–angiotensin–aldosterone (RAAS) inhibitors and 10–20% were not receiving anticoagulants, in contrast with guideline recommendations [18–21]. This evidence concerns the gene REN and diabetes mellitus.