Is the Way to Someone's Heart Through Their Stomach? The Cardiorenal Paradox of Incretin-Based Hypoglycemic Drugs in Heart Failure

Incretins are endogenous insulin secretagogues that are synthesized in the gastrointestinal tract and released by eating. Incretin mimetics (glucagon-like peptide-1 [GLP-1] receptor agonists) cause prolonged stimulation of the GLP-1 receptor, whereas incretin enhancers (DPP-4 [dipeptidyl peptidase-4] inhibitors) intensify the action of endogenous GLP-1 by blocking its degradation. The responses to these 2 incretin-based classes of drugs are both overlapping and distinct. 1 The supraphysiological stimulation of GLP-1 receptors produced by agonists (eg, exenatide and liraglutide) is greater than that after the modest potentiation of GLP-1 that results from inhibition of DPP-4. Conversely, the actions of DPP-4 inhibitors (eg, sitagliptin and saxagliptin) may be modulated by the augmentation of endogenous peptides in addition to GLP-1.