Cardiovascular disease is the predominant cause of death in diabetic patients, and yet the cardiovascular benefits of traditional drug treatments for
hyperglycemia have been elusive. Two new classes of diabetic drugs targeting the
glucagon-like peptide-1 (GLP-1)
incretin pathway have emerged. The
GLP-1 receptor agonists reduce
blood glucose levels by stimulating
insulin and inhibiting
glucagon secretion and gastric emptying. Dipeptidyl peptidase-4 (DPP-4) inhibitors prolong the half-life of endogenous
GLP-1 by inhibiting its proteolytic degradation to the metabolite
GLP-1(9-36), thereby increasing
insulin and reducing
glucagon secretion. Here, we review the biology of
GLP-1, including studies of
GLP-1 in animal models and humans with
heart disease. We also highlight the emerging salutary cardiovascular effects of both
GLP-1 and
GLP-1(9-36). Unlike the GLP-1R agonist
Exendin-4, both
GLP-1 and
GLP-1(9-36) exert vasodilatory actions on coronary and peripheral mouse vessels. Importantly, the effects of
GLP-1 on isolated hearts undergoing experimental
ischemia and preconstricted mesenteric arteries were reduced but not abolished by the
DPP-4 inhibitor Sitagliptin. We posit that GLP-1-based
therapeutics represent novel and promising anti-diabetes drugs, the direct cardiovascular actions of which may translate into demonstrable clinical benefits on cardiovascular outcomes.