Whereas GLP-1 agonists reduced the risk of myocardial ischemia and heart failure in the early studies [43, 44], no reduction in heart failure risk was observed in the HARMONY [24], EXSCEL [25], LEADER [26], ELIXA [27], or SUSTAIN-6 [28] trials despite the substantially lower HbA1c concentrations in the treatment group than in the placebo group. This evidence concerns the gene GCG and myocardial ischemia.