Among adults with type 2 diabetes and advanced kidney disease, starting an SGLT2 inhibitor is linked to a 6% lower risk of heart failure than starting a GLP-1 receptor agonist, while the risks of...
Mechanism
Synthesis from 1 study
SGLT2 inhibitors make the kidneys flush out more sugar and water, which lowers blood volume and reduces pressure on the heart. This makes it easier for the heart to pump and less likely to fail. GLP-1 agonists don’t do this, so they don’t lower heart failure risk the same way.
Most probable mechanism
When the kidneys filter less sugar back into the blood, more sugar and water leave the body as urine. This lowers the total fluid volume in the blood, which reduces the pressure on the heart and makes it easier for the heart to pump. The heart then uses less energy and is less likely to fail.
SGLT2 inhibitors block glucose reabsorption in the proximal tubule of the kidney, increasing urinary glucose excretion
Increased urinary glucose excretion creates an osmotic gradient that promotes natriuresis and diuresis, reducing plasma volume and venous return
Reduced plasma volume decreases left ventricular filling pressure and cardiac preload
Lower preload reduces myocardial wall stress and oxygen demand in the heart
Reduced myocardial oxygen demand lowers the risk of heart failure decompensation in the setting of chronic kidney disease and metabolic stress
Evidence from Studies
Supporting (1)
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Contradicting (0)
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