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102 Several works have reported that the levels of eNAMPT, mostly in adipose tissue but also in plasma, correlate with the levels of inflammatory cytokines

instead, the multisystem pathologic processes that are associated with this condition have long been well established as drivers of its clinical presentation and outcomes.470 One could argue that the success of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and now of GLP-1RAs, suggests that metabolic abnormalities play an important role in driving HFpEF.470 SGLT2 inhibition is also known to benefit patients with heart failure and a reduced ejection fraction.471 The mechanisms by which SGLT2 inhibitors treat heart failure include lowering blood glucose levels by inhibiting the SGLT2 protein in the renal tubules and reducing glucose reabsorption in the tubules.472 Promoting the urinary excretion of sodium and water reduces fluid retention and hypervolaemia, thereby reducing the load on the heart.473 It also improves myocardial energy metabolism, increases fatty acid oxidation in the myocardium, and improves myocardial energy supply.474 Moreover, these agents reduce the risks of myocardial inflammation and fibrosis and improve cardiac structure and function.475 By the way, a clinical study published in Nature Metabolism detailed the effects of semaglutide and dapagliflozin (an SGLT2 inhibitor) on blood sugar control in patients with T2DM of different pathophysiological types.476 It was found that semaglutide performed better than dapagliflozin in reducing HbA1c levels.476 The study results suggest that semaglutide may be a more suitable choice for patients with severe insulin deficiency, while dapagliflozin might be effective for a broader range of patients with metabolic abnormalities.476 If SGLT2 inhibitors and GLP-1RAs are effective in patients with heart failure (regardless of whether the ejection fraction is reduced or preserved), the commonalities between the two types of heart failure may be greater than is often thought

Kjellberg J, et al

He advises taking a magnesium supplement (such as magnesium citrate or oxide) in the evening at a dose starting around 300 milligrams with a full glass of water before bed to help stimulate a bowel movement the next morning

And it seems that GIP, we can either agonize it or antagonize it