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International study reveals surprising twist in how diabetes drugs help the heart

• International study, led by researchers in Singapore and Germany, unveils unexpected mechanisms of SGLT2 inhibitors, challenging the assumption that their beneficial, organ-protective effects stem from a diuretic effect.
• Insights suggest the drugs, which have been developed to treat diabetes but are meanwhile widely used for chronic kidney disease and heart failure, trigger ancient and highly conserved evolutionary survival signals that may also contribute to longer healthspans.

SINGAPORE, 27 May 2024 – A randomised, placebo-controlled clinical trial led by a collaboration between Duke-NUS Medical School, National Heart Centre Singapore (NHCS) and Klinikum Nürnberg, Germany, has revealed surprising new insights into how SGLT2 inhibitor drugs, originally developed for diabetes, benefit patients with heart failure. Contrary to common assumptions, these drugs may improve cardiac outcomes and heart health without acting as diuretics.

Heart failure is a condition where the heart cannot pump enough blood to meet the body’s demands, often leading to fluid build-up in tissues and congestion of the blood circulation. This congestion strains the heart and causes symptoms like breathlessness and swelling. Reducing congestion is key to managing heart failure, as it reduces the workload of the heart and thereby eases pumping.

SGLT2 inhibitor drugs are the new blockbuster treatment for chronic heart failure because they very quickly stabilise heart function and reduce hospitalisations and patient deaths. The drugs release more glucose into the urine, and thereby have the potential to pull more fluid from the body into the urine, alleviating the congestion experienced by patients with heart disease. Given this diuretic potential, leaflets accompanying the drugs list dehydration as a common side effect of their use.

However, results from this clinical trial, published in the Journal of the American College of Cardiology, cast doubt on the presumed diuretic action of SGLT2 inhibitors in patients with heart failure.

First author Dr Adriana Marton, Visiting Senior Research Fellow with the Cardiovascular & Metabolic Disorders Programme at Duke-NUS, who kicked-off this pilot study in Singapore, said:

“Many experts who relied on the idea that SGLT2 inhibitors act as diuretic drugs raised their eyebrows when we first reported our data, showing that the body instead activates a very elegant defence mechanism that almost entirely abolishes the potential diuretic effects of these drugs.”  Read more>>

Source: 
https://www.duke-nus.edu.sg/newshub/media-releases/international-study-reveals-surprising-twist-in-how-diabetes-drugs-help-the-heart

https://pubmed.ncbi.nlm.nih.gov/38599715/