The architecture of HF therapy recently went on a pillar building mode .Some are strong and evidence based , still, few of the pillars are still shaky. We know the terrain for pillar building in HFpEF is much more difficult . Now, Tirzepatide seems to be a God-made molecule. It is found to be useful in HFpEF. This study (Krüger N, et al Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 ) is from Boston, Massachusetts, adding some credibility. Read yourself and to see whether it is really sturdy or shaky pillar.
The Gut-Heart connection
There is not much connection really. We want to connect it through Semaglutide and Tirzepatide through its antidiabetic and anti-obesity properties .How does this gut hormonal agents work in HF ? These drugs are analogues of glucagon-like peptide or gastric inhibitory polypeptide. These drugs can be called intestinal sedatives, slow down gastric emptying, reduce appetite, and hence weight loss and also diabetic control. They are secreted from K and L cells of the intestine.
The K cell the L cell (Kuhre RE, 2021 )
Glucose dependent insulinotropic polypeptide (GIP) is secreted from K cells, which are predominantly found in the duodenum, whereas glucagon-like peptide-1 (GLP-1) is secreted from L cells, which increase in numbers in the distal intestine. Both cell types are so-called open enteroendocrine cells with direct contact to the intestinal lumen, allowing sampling of the chyme and regulate food movement and modulate insulin secretion.
Final message
Weight reduction and diabetes control are indeed vital cogs in the management of both HFrEF as well as HFpEF (more so in the latter). There are number of simple, cheap and less-glamorous ways available to reduce weight.
At any point of imagination, Tirzepatide (Mounjaro) can not claim to be an anti-cardiac failure medication. Even SGLT-2 is just a glorified glycosuric drug, stealing the credit from diuretics .
It is important to realsie, as per our past track record, the side effects of all these weight losing drugs, would knock our doors, only after a year or two.
Reference
Dr.S.Venkatesan MD 