Weight Loss Drug Shrinks Heart Muscle in Mice and Human Cells

Weight loss drugs like semaglutide may shrink heart muscle as well as waistlines, according to a study from the University of Alberta.

The research, published in JACC: Basic to Translational Science, found that the popular drug decreased heart muscle mass in lean and obese mice as well as in lab-grown human heart cells.

Semaglutide can cause muscle loss

Virtually no drug comes without side effects. The weight loss drug semaglutide, also known as Ozempic®, successfully helps people lose body weight. But this comes at the cost of side effects such as nausea and gastrointestinal problems.

However, reports suggest semaglutide may have other side effects, including the loss of skeletal muscle. Up to 40% of drug-induced weight loss is actually muscle loss, according to a Lancet study published in November.

This rate of muscle loss is much higher than what would occur with a calorie-reduced diet or through the normal aging process, spelling potential future health issues such as decreased immunity, increased infection risk and poor wound healing.

In a new study, researchers using experimental mouse models to investigate muscle loss discovered that heart muscle also shrank in animals taking semaglutide, but without negatively impacting heart function.

Changes in heart mass, but not function

The researchers used a mouse model of obesity by feeding male mice a high-fat, high-sucrose diet over several weeks before switching to a “standard” mouse diet to simulate how someone may reduce their calorie intake.

They then treated mice with semaglutide or a control. After 3 weeks, the drug-treated mice lost ~30% of their body weight and ~65% of their fat mass compared to the non-treated mice.

However, their hearts did not fare so well. The semaglutide-treated mice lost a significant amount of mass in their left ventricles – the heart’s main pumping chamber that sends oxygen-rich blood to the rest of the body – as well as their overall heart weight. The overall surface area of their heart cells was also reduced.

The heart’s pumping ability and how well the heart relaxes and fills with blood between beats were unaffected, suggesting that heart function was unaffected by this short treatment period.

Mouse experiments also showed negative effects of semaglutide on skeletal muscle in lean mice – there were no overt changes in their body weight, but they lost 8.2% of skeletal muscle mass over the same 3-week treatment period. They also saw similar changes consistent with the obese mice – i.e., reduced left ventricular mass and overall heart weight as well as no change in pumping ability.

Experiments on lab-grown human heart cells found that the cells’ surface area decreased after 24 hours of semaglutide treatment, consistent with the mouse study. Nevertheless, more research is necessary to see if the drug also decreases heart mass in humans.

Implications may go further than just weight loss

Muscles release signal molecules called myokines that help support the immune system to fight infection – meaning muscle loss isn’t just about losing physical strength, but our wider health as well.

Loss of skeletal muscle can also worsen health conditions like sarcopenic obesity, where individuals have a high amount of body fat with low skeletal muscle mass. This could have such knock-on effects as increasing cardiovascular disease and mortality rates.

Overall, the paper’s findings may therefore serve as a cautionary tale for people taking the drug who are not classed as obese or who do not have cardiovascular disease, as some effects may emerge with longer-term use.

The researchers recommend that these findings should be confirmed in patients taking semaglutide and similar drugs, especially given the growing number of people receiving them, suggesting “cardiac structure and function be carefully evaluated in previous and ongoing clinical studies.”

Reference: Martens MD, Abuetabh Y, Schmidt MA, et al. Semaglutide reduces cardiomyocyte size and cardiac mass in lean and obese mice. J Am Coll Cardiol Basic Trans Science. doi: 10.1016/j.jacbts.2024.07.006