Could an Exercise Pill Replace Workouts? A Look at Exercise Mimetics

What if taking a daily pill could boost your metabolism, help you shed pounds and extra fat, and improve your endurance — basically, all the perks of training for a marathon but without the blisters, sore muscles, or even running a single mile? 

Enjoying the health benefits of exercise without breaking a sweat may sound too good to be true, but a new class of drugs called exercise mimetics may transform the way we approach exercise and weight loss in the not-too-distant future.

Although the drugs are still in the early stages of development, many experts believe that within the next five years, exercise mimetics may be able to treat overweight and obesity, type 2 diabetes, and the muscle loss that comes with getting older.

But unlike GLP-1 weight loss medications such as Ozempic, exercise mimetics don’t impact digestion or reduce appetite. Instead, they boost metabolism in the same way that training for a marathon would.

How Do Exercise Mimetics Work?

When you exercise, your body starts adapting to the stress of the increased activity, setting off a series of events. Your muscles and bones get stronger, and the muscles require increased energy (in the form of calories) so you can continue to exercise, says Thomas Burris, PhD, a professor and researcher at the University of Florida College of Pharmacy in Gainesville. This is where exercise mimetics are a game-changer: According to Dr. Burris, they “turn on” some of the same genes that get activated during exercise.

Burris led research on one of the most promising in the new class of drugs, SLU-PP-332, in a September 2023 study published in The Journal of Pharmacology and Experimental Therapeutics. The study examined the effects of the exercise mimetic in mice. Results showed the drug targets a group of proteins in the body called estrogen-related receptors, which are more active when people exercise. But in this case, it’s the drug — not exercise — that causes increased energy expenditure (calorie burning) in tissues like muscles, the heart, and the brain, says Burris.

A Closer Look at SLU-PP-332

When mice are treated with SLU-PP-332, the effect on their metabolism is similar to what we see in people when they’re fasting or exercising — and they lose a significant amount of weight, says Burris.

In the study, mice with obesity were all exercised and fed the same amount, but the mice who were treated with the drug twice a day for one month lost 12 percent of their body weight and gained 10 times less fat compared to the untreated mice.

“The drug leads the body to use more energy/calories than what it would normally burn without the drug. You see this with athletes who consume a lot of calories but still lose weight. It’s not just because they are burning a lot of calories during their workouts — it’s that they’re burning a lot more calories in their downtime, too,” says Burris.

In addition to reducing the amount of obesity, the drug leads to better overall metabolic health, including improvements in type 2 diabetes by improving insulin sensitivity, he adds.

Will Exercise Mimetics Work on Humans?

Although the drug has been successful in mice, the question remains as to whether it will work on humans, says Burris. “We won’t know for certain until we do it, but when we look at the set of genes that are turned on, this is the same set of genes that are turned on in humans. The thought is that these effects would carry over and translate into humans.”

Researchers are optimistic about the results so far, and Burris and his team hope to start testing their drug on humans within the next two years. 

Potential Benefits and Risks of Exercise Mimetics 

The health benefits of exercise mimetics aren’t limited to their impact on overweight or obesity or even metabolic health in general, because the effects of exercise reach every organ and system in the body, says Anthony Hannan, PhD, professor and researcher at the Florey Institute of Neuroscience and Mental Health at the University of Melbourne in Australia.

“We hope that exercise mimetics may help in many of the ways that exercise can, including actions on the muscles, heart, brain, and bones,” says Dr. Hannan.

Hannan has co-authored research that explores the possibility of someday leveraging exercise mimetics to improve brain function and treat central nervous system disorders such as dementia. 

Exercise mimetics could also be used to treat the muscle loss — and the accompanying risks — that naturally occur with aging. “If you’re sedentary, especially as you age, there’s a risk of injury when you try to be more active. But if the muscle has more endurance because of taking the exercise mimetic, we suspect that the chance of an injury or fall or something like that would probably be reduced,” Burris says, adding that more research is needed to confirm that theory. 

Is there a downside to exercise mimetics? The potential risks of the drugs are still being explored. One concern is that a drug-induced “metabolic overdrive” for long periods of time could have unintended — and negative — health effects and eventually make it harder for muscles to repair and regenerate.

Could a Pill Ever Replace Exercise?

“Exercise pill” skeptics point out that there is no single “exercise gene” or pathway and that physical activity leads to a multitude of direct and downstream benefits that could never be replicated by a single drug.

Burris agrees that even though exercise mimetics can provide many benefits, they can’t do it all. “For example, weight-bearing exercise (such as dancing, hiking, jogging, or tennis) can cause an increase in bone density, which helps prevent fractures, especially in older adults. Right now there isn’t any data that would suggest that exercise mimetics would be able to achieve these same benefits,” he says.

The drugs wouldn’t be able to replicate hours spent pumping iron, either. “On their own, the drugs wouldn’t lead to the appearance of bigger muscles — they mimic the effects of endurance exercise, not resistance exercise,” says Burris.  

New Drugs Could Motivate People to Be More Active

Rather than completely replacing physical activity, exercise mimetics could provide some motivation for people who have a hard time exercising and/or lack endurance, says Burris.
 
“Imagine if a treatment existed that gave a big boost of extra endurance. How many more people might be willing to go out and do something? It could help remove some barriers if a person could go out and have a nice long walk and not feel winded or have tired muscles afterward,” he says.

 
Editorial Sources and Fact-Checking 

• Billion C, Schoepke E, Avdagic A, et al. A Synthetic ERR Agonist Alleviates Metabolic Syndrome. The Journal of Pharmacology and Experimental Therapeutics. September 22, 2023.
• Gubert C and Hannan AJ. Exercise Mimetics: Harnessing the Therapeutic Effects of Physical Activity. Nature Reviews Drug Discovery. June 8, 2021.
• Hawley JA, Joyner MJ, and Green DJ. Mimicking Exercise: What Matters Most and Where to Next? The Journal of Physiology. November 20, 2019.