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Weight loss drugs such as Ozempic and Wegovy, known for their action as GLP-1 receptor agonists, are hailed for their immediate effects on metabolic health. However, recent studies reveal adverse effects on cardiac muscle mass, although the long-term implications are still unclear. This discovery, however, raises questions about the safety of these treatments for people suffering from cardiovascular disease.
GLP-1 receptor agonists, such as semaglutide, mimic a hormone that stimulates insulin production, thereby reducing blood sugar and appetite. They are approved for treating type 2 diabetes and helping with weight management, while providing significant cardiovascular benefits, including reducing the risk of major cardiovascular events. However, little research has looked at the impact of these drugs on heart tissue, which is made up of specific muscles essential for pumping blood.
It was therefore relevant, given the increasing use of this type of medication, to explore why this research is lacking and to attempt to fill these gaps. In this sense, the University of Alberta, which recently conducted a study aimed at administering semaglutide to healthy and obese mice, revealed a notable decrease in the mass and size of cardiac muscle cells. Although this phenomenon was observed without alteration of overall cardiac function, the study does not indicate whether or not this absence of alteration is maintained in the long term.
Unexpected effects
The results of this experiment on mice were corroborated by tests in vitro on human cells, where a similar reduction in cardiomyocyte size was observed. These results indicate a specific effect of semaglutide on cardiac cells, independent of weight variations. This raises concerns about the potential long-term effects in humans, where such a reduction could prove detrimental, especially for people suffering from existing cardiovascular conditions.
On the left, cardiomyocytes from the left ventricle of mice that did not receive semaglutide treatment. Right: cardiomyocytes from semaglutide-treated mice. © Martens et al., The Lancet, 2024
Experts from the American Heart Association therefore emphasize the need for rigorous evaluation of the effects of GLP-1 agonists on muscle health. They call for more objective studies to fully understand the impact of these drugs on cardiac structure and function, as indicated by research conducted by the organization recently published in their journal Circulation.
Although reduction in cardiac mass may be beneficial in the presence of pro-hypertrophic stimuli, it could have negative consequences in the absence of these factors. Future research could therefore focus on assessing whether interventions such as diet or exercise can compensate for these losses, as appears to be the case for skeletal muscle mass, the researchers say.
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Towards a better understanding of risks
Overall, the results suggest that people with muscle atrophy or cardiovascular disease may be at increased risk with the use of drugs like Ozempic. Therefore, the researchers advocate in their paper that it is essential to carefully evaluate cardiac structure and function in current and future clinical studies to ensure the safety of treatments.
While GLP-1 drugs continue to attract interest for their metabolic benefits, caution remains necessary, and additional research is needed to ensure that these treatments do not compromise patients’ overall health.
