The landscape of novel antidiabetic drugs in diabetic HFpEF: relevant mechanisms and clinical implications

Figures

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  Fig. 1. The pathophysiology of DM with HFpEF. DM patients are accompanied with endothelial function injury, abnormal fatty acid metabolism and dysregulation of glucose metabolism. Among them, endothelial function injury leads to coronary microvascular dysfunction, myocardial fibrosis and sustained increase of ventricular filling pressure; abnormal fatty acid metabolism contributes to myocardial lipotoxicity, oxidative stress, and mitochondrial dysfunction; dysregulation of glucose metabolism results in an increase in reactive oxygen species (ROS), the activation of inflammatory pathways and reduction of cardiac energy efficiency, which ultimately prompts the development of HFpEF

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  Fig. 2. The mechanisms of novel antidiabetic drugs in diabetic HFpEF via inflammation, oxidative stress and lipotoxicity. Novel antidiabetic drugs could reduce inflammation, oxidative stress, apoptosis and lipotoxicity, by activating several signaling pathways, including AMPK/mTOR, AMPK/PGC-1α, Sirt1/AMPK, or by inhibiting certain signaling pathways, such as JAK/STAT, RhoA/ROCK, mTOR/HIF-1α and ROCK/PPARα pathway, ultimately improving diabetic HFpEF

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  Fig. 3. The relevant mechanisms of the novel antidiabetic drugs in diabetic HFpEF through mitochondrial dysfunction, autophagy and ferroptosis. Novel antidiabetic drugs mitigated mitochondrial dysfunction and ferroptosis, as well as promoted autophagy by activating Xc−/GSH/GPX4 axis and SIRT3-mediated autophagic pathway, or by inhibiting TGF-β/Smad pathway, ultimately improving diabetic HFpEF