New Antihyperglycemic Drugs and Heart Failure: Synopsis of Basic and Clinical Data

Figure 2

Interactions of antidiabetic drugs with cardiomyocytes: the well-established downstream mechanism of GLP-1 receptor agonists alters intracellular Ca²⁺ transients via a PKA-dependent activation of L-type Ca²⁺ channels and Epac2-dependent activation of the ryanodine receptor. For empagliflozin, potential downstream mechanisms are still unknown, yet there is strong evidence that the Ca²⁺ homeostasis is influenced. Possible downstream mechanisms of DPP-4 inhibitors are also still unknown. The wide interactions with cardiomyocytes via miscellaneous second messengers are not shown. (Na⁺-ch: voltage gated sodium channel, K⁺-ch: voltage gated potassium channel, Ryr; ryanodine receptor, NCX: sodium-calcium exchange pump, and NKA: sodium-potassium exchange pump).