Weight-loss drugs lower impulse to eat – and perhaps to exercise too

Semaglutide – the drug in medications like Ozempic and Wegovy – causes mice to exercise less. The finding suggests these weight-loss medications may reduce people’s motivation to work out.

Semaglutide helps treat type 2 diabetes and obesity by mimicking a hormone called GLP-1, which regulates blood sugar and suppresses appetite. GLP-1 also dampens activity in the brain regions involved in reward processing and cravings. This may explain why people on semaglutide-based medications don’t find eating as rewarding or pleasurable as they did before taking the drugs. Also, it is probably why some studies have indicated semaglutide might help treat substance use disorders as well.

Ralph DiLeone at Yale University and his colleagues wanted to know whether semaglutide affects other rewarding behaviours too, such as exercise – which is known to improve mood and memory. So they treated seven mice with semaglutide and an equal number with a placebo for a week and measured how far the animals ran on an exercise wheel each day.

On average, those treated with semaglutide ran about half the distance of those given a placebo, suggesting they may have a lower motivation to exercise.

To further validate this, the researchers treated a separate group of 15 mice with semaglutide and another equal-sized group with a placebo for five days and explored their willingness to exercise on a wheel. However, this time, the exercise wheel periodically locked up while the animals were running on it. To unlock it, the mice had to press a lever with their nose. Each time the wheel locked, it became progressively more difficult to unlock, requiring the mice to press the lever additional times. “Eventually they quit,” says DiLeone, who presented these findings at a Society for Neuroscience meeting in Chicago on 7 October. “We call that their break point, and it gives us a surrogate for how motivated they are to access running wheels.”

The maximum number of times mice treated with semaglutide pressed the lever was, on average, 25 per cent less than that of animals in the control group. The researchers repeated the experiment with obese mice and found similar results.

Together, these findings suggest that semaglutide-based medications such as Ozempic or Wegovy may reduce motivation to exercise, similar to how they reduce cravings for food or drugs. However, there hasn’t been any evidence indicating that this is the case in people, says DiLeone. This may be because most data on Wegovy and Ozempic comes from people enrolled in weight loss programmes that include exercise, he says.

Still, these findings underscore the potential of these drugs to interfere with positive behaviours, not just negative ones.“[This] data suggests there are still motivated behaviours that may be altered [with semaglutide] that we haven’t asked about yet,” says Karolina Skibicka at The Pennsylvania State University.