Drugs Like Ozempic May Have a Shrinking Effect on The Heart

Popular weight loss drugs like Ozempic and Wegovy are showing incredible short-term benefits – from boosted metabolic health to pain relief to addiction and cognitive health.

These are really promising initial signs, but it's important to remember the long-term side effects are still coming to light.

Recently, some experts have raised concerns that novel weight loss drugs – known as glucagon-like peptide-1 (GLP-1) receptor agonists – could be causing significant skeletal muscle loss as well as fat loss. But there's not enough data to say for sure.

Now, researchers at the University of Alberta in Canada have added to the discussion by bringing up a subset of muscles that only exist in the heart.

Cardiac muscles are what keep our hearts pumping blood around our bodies, and yet little research has investigated how these tissues deal with GLP-1 agonists.

For 21 days, researchers at Alberta administered semaglutide – the active ingredient in Ozempic – to both lean and obese mice without diabetes or cardiac dysfunction.

The obese mice lost about 30 percent of their body weight and 65 percent of their fat mass compared to untreated mice.

Among lean mice that were treated with semaglutide, researchers noted a roughly 8 percent reduction in skeletal muscle over the course of three weeks.

While there were no observed changes to heart function or the thickness of heart walls, both groups of mice treated with semaglutide showed decreases in overall heart mass and the individual size of their heart muscle cells.

"Together," the authors conclude, "these data indicate that the reduction in cardiac size induced by semaglutide occurs independent of weight loss."

To explore further, the team of researchers, led by clinical scientist Matthew Martens, turned to human cells. In the lab, when human cardiac muscle cells were treated with semaglutide, they showed significant reductions in size.

The cardiomyocyte area of mice without semaglutide treatment (left) and with semaglutide treatment (right). (Martens et al., The Lancet, 2024)

Given these results, the authors admit it is tempting to speculate that semaglutide is responsible for cardiac shrinkage and atrophy. "However," they note, "we do not observe any changes in recognized markers of atrophy."

The means they cannot be certain semaglutide is causing the atrophy of cardiac muscles, or even if this loss of muscle is a bad thing. In some cases, it could possibly confer benefits.

Nevertheless, the findings among mice and human cells suggest that semaglutide "has the potential to be detrimental in the long term" to heart muscles.

If the findings translate to living humans, then it means people with existing cardiovascular disease or muscle atrophy could be placing their hearts at added risk if they are prescribed semaglutide or similar drugs.

It's unknown whether diet or exercise can offset these potential heart muscle losses, but that is something future research should investigate, as this seems to be the case with skeletal muscle loss.

"We suggest that cardiac structure and function be carefully evaluated in previous and ongoing clinical studies," Martens and his colleagues at Alberta conclude.

The call to action is supported by another recent paper, published in a journal run by the American Heart Association, whose authors argue the effects of GLP-1 agonists on muscle health should be studied in a "more objective and comprehensive" way, especially given "the substantial numbers of patients who will likely be taking these medications well into the future."

The study was published in The Lancet.