Variable effects of anti-diabetic drugs in animal models of myocardial ischemia and remodeling: A translational perspective for the cardiologist

Diabetes and heart failure are very prevalent, and affect each other's incidence and severity. Novel therapies to reduce post-myocardial infarction (MI) remodeling that progresses into heart failure are urgently needed, especially in diabetic patients. Clinical studies have suggested that some oral anti-diabetic agents like metformin exert cardiovascular protective effects in heart failure patients with diabetes, whereas other agents may be deleterious. In the current review, we provide an overview of the cardio-specific effects of oral anti-diabetic drugs in animal models of acute MI, post-MI remodeling, and heart failure. Metformin has consistently been shown to ameliorate cardiac remodeling after ischemia/reperfusion (I/R) injury, as well as in several models of heart failure. Sulfonylurea derivatives are controversial with respect to their direct effects on the cardiovascular system. Thiazolidinediones protect against myocardial I/R injury, but their effects on post-MI remodeling are less clear and clinical studies raised concerns about their cardiovascular safety. Glucagon-like peptide-1 analogs have potential beneficial effects on the cardiovascular system that require further confirmation, whereas the results with dipeptidyl peptidase-4 inhibitors are equivocal. Current clinical guidelines, in the absence of prospective clinical trials that evaluated if certain oral anti-diabetic agents are superior over others, only provide generic recommendations, and do not take into account interesting experimental and mechanistic data. The available experimental evidence indicates that some anti-diabetic agents should be preferred over others if cardio-protective effects are warranted. These experimental clues need to be confirmed by clinical trials.