If exercise isn’t exactly your favourite way to spend your free time, the idea of getting some of its benefits from a pill probably sounds pretty appealing.
And while we’re a long way from replacing workouts with medication, scientists have developed a pill designed to mimic one of the biological effects of exercise – and it has now completed its first trial in humans.
The drug, called ENV-308, is designed to mimic the effects of a molecule produced by the body during intense exercise. Early results are intriguing, particularly because its developers hope it could eventually help people manage their weight while preserving muscle mass.
Naturally, that raises comparisons with GLP-1 medications such as semaglutide and tirzepatide. But ENV-308 is at a very early stage of development, and we don’t yet know whether it actually helps people lose weight.
So, how does this so-called ‘exercise pill’ work – and could it eventually offer an alternative to GLP-1s? Here’s what experts say.
Meet the experts: Christine Bonarrigo, PharmD, weight management clinical pharmacist at Tufts Medical Center; Dr Paul Sack, endocrinologist at MedStar Health; Dr Mir Ali, medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in California.
What has the ENV-308 trial found so far?
The news comes from results of a Phase 1 clinical trial involving 88 healthy adults.
Crucially, this trial wasn’t designed to determine whether ENV-308 helps people lose weight. Instead, researchers were primarily assessing the drug’s safety and tolerability.
The company reported that participants tolerated the medication ‘well’, with what it described as an ‘exceptional’ gastrointestinal safety profile. That’s particularly notable given that nausea, vomiting and other gastrointestinal side effects can occur with GLP-1 medications.
None of the participants experienced serious side effects or stopped taking the medication during the trial.
Researchers also looked at ENV-308’s effect on leptin, a hormone released by fat cells that plays a role in appetite regulation. People with obesity often have chronically elevated leptin levels, and the trial found that ENV-308 reduced circulating leptin.
However, it’s important not to read too much into that result. The findings don’t show that ENV-308 causes weight loss or improves leptin sensitivity.
The company hopes the medication could eventually help people maintain weight loss while preserving muscle mass, but that has yet to be demonstrated in humans.
How does the ‘exercise pill’ ENV-308 work?
ENV-308 is designed to mimic the effects of a molecule called Lac-Phe, which the body produces during intense exercise and after eating.
Lac-Phe has been linked with appetite suppression, but the molecule is cleared too quickly by the body in its natural form to be useful for weight loss or weight maintenance.
ENV-308 aims to recreate some of those effects in a once-daily oral medication.
Calling it an ‘exercise pill’, then, requires a pretty substantial caveat: it isn’t designed to reproduce all the benefits of exercise. Rather, it targets one biological pathway associated with intense exercise.
How is ENV-308 different from GLP-1 medications?
ENV-308 and GLP-1 medications work through very different biological pathways.
‘GLP-1 medications such as semaglutide and tirzepatide act on incretin pathways that regulate appetite, blood sugar, and digestion,’ explains Bonarrigo. ‘ENV-308 is an investigational oral drug designed to mimic Lac-Phe, a signalling molecule produced by the body after intense exercise.’
The pathway targeted by ENV-308 is ‘very different’ from that targeted by GLP-1s, says Dr Sack.
And there’s another major difference: the amount of evidence we have.
‘It has only been shown to cause weight loss without losing muscle mass in animal studies,’ says Dr Sack.
So while the early safety data is encouraging, it’s far too soon to know how ENV-308 will compare with existing weight-loss medications.
‘The recent Phase 1 results provide encouraging preliminary safety and tolerability data, but we don’t yet have human data showing how much weight ENV-308 can help people lose,’ says Bonarrigo.
Could ENV-308 help preserve muscle during weight loss?
Potentially – but again, this hasn’t yet been demonstrated in humans.
ENV-308 is being developed for people with obesity, and Dr Ali says it could potentially prove useful for those who want to lose a significant amount of weight but are concerned about muscle loss or gastrointestinal side effects.
But it may not necessarily compete directly with GLP-1 medications.
‘It seems that it’s more designed to complement GLP-1s or maybe for maintenance after weight loss,’ Dr Ali says.
Further clinical trials will be needed to determine whether ENV-308 actually produces meaningful weight loss in people with obesity, whether it helps preserve muscle mass and how its effects compare with existing treatments.
When could ENV-308 become available?
Not anytime soon.
While the idea of getting some exercise-like effects from a pill is understandably appealing, ENV-308 remains at a very early stage of clinical development.
‘We don’t even know what the weight loss effects or changes in muscle mass will be in obese individuals,’ says Dr Sack.
Even if future clinical trials are successful, Dr Ali says it will likely be ‘years’ before the medication becomes available to the general public.
For now, then, there’s no pill that can replicate the wide-ranging benefits of physical activity. Exercise remains important not only for weight management, but for cardiovascular fitness, strength, bone health and brain health – benefits that ENV-308 hasn’t been shown to reproduce.
Korin Miller is a freelance writer specializing in general wellness, sexual health and relationships, and lifestyle trends, with work appearing in Men’s Health, Women’s Health, Self, Glamour, and more. She has a master’s degree from American University, lives by the beach, and hopes to own a teacup pig and taco truck one day.
Carina Hsieh, MPH, is the deputy features editor of Women’s Health. She has more than a decade’s worth of experience working in media and has covered everything from beauty, fashion, travel, lifestyle, pets, to health.
She began her career as an intern in the fashion closet at Cosmopolitan where she worked her way up to Senior Sex & Relationships Editor. While covering women’s health there, she discovered her passion for health service journalism and took a break to get her Masters in Public Health. Post-grad school, she worked as a freelance writer and as The Daily Beast’s first Beauty, Health, and Wellness Reporter.
Carina is an alum of the Fashion Institute of Technology and the Yale School of Public Health. She and her French Bulldog, Bao Bao, split their time between Brooklyn and Connecticut. She enjoys reformer Pilates, (slow) running, and smelling the fancy toiletries in boutique fitness class locker rooms.