Effects of Empagliflozin on Gut Microbiota in Heart Failure with a Preserved Ejection Fraction: The Design of a Pragmatic Randomized, Open-Label Controlled Trial (EMPAGUM)

Abstract

Although empagliflozin has been recommended for individuals with heart failure, its effects on heart failure with preserved ejection fraction (HFpEF) remain uncertain from a physiopathological standpoint. The metabolites produced by gut microbiota have been shown to have a crucial role in the development of heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT2) have been shown to change the make-up of the gut microbiota in rodent studies. There is mixed evidence from similar studies investigating whether or not SGLT2 can affect the microbiota in the human gut. This trial is a pragmatic, randomized, open-label controlled study with empagliflozin as an intervention. We will enroll 100 patients with HFpEF and randomly assign them to one of two groups to receive either empagliflozin or a placebo. Patients in the Empagliflozin group will be given 10 mg of the drug daily, while those in the Control group will not be given empagliflozin or any other SGLT2. The purpose of the trial is to validate the changes that occur in gut microbiota in patients with HFpEF who take empagliflozin and to investigate the function of gut microbiota and their metabolites in the process.

Gut microbiota: a potential new regulator of hypertension

“…When the intestinal barrier function is normal, the intestinal permeability is low, which can effectively inhibit the leakage of intestinal pathogens, intestinal endotoxin, and other substances into the body. Abnormal changes in intestinal permeability and structural damage to the intestinal mucosa lead to the translocation of bacteria and toxic products into the blood circulation, causing the development of systemic inflammation ( 17 ). Chronic inflammation can perpetuate the hypertensive state, exacerbate hypertensive target organ damage, and promote the development of resistant hypertension ( 18 ).…”