Drug mimics a hormone you make when you push hard at the gym – early results suggest it could help to keep weight off after stopping GLP-1s.
There’s a hormone your body releases when you go hard on a run or push through a tough set at the gym. It’s called Lac-Phe, and scientists only pinned down what it actually does back in 2022, when Stanford’s Jonathan Long and his team traced it to the way intense exercise suppresses appetite. It’s one of the molecular reasons a hard workout can leave you less hungry, not more.
The problem: your body clears Lac-Phe out of your system almost as fast as it makes it. That made it useless as a medicine, at least until now.
Enveda, a Colorado-based biotech company, has built a pill called ENV-308 designed to mimic what Lac-Phe does in the body, but in a form that sticks around long enough to actually work as a once-daily treatment [1]. The company just reported its first human safety results, and they’re the kind of quietly good news that tends to matter a lot down the line.
The GLP-1 problem nobody’s fully solved
To understand why this pill matters, you have to understand the hole it’s trying to fill. GLP-1 drugs have become the biggest story in weight management in years, with roughly 1 in 8 U.S. adults reportedly using them. But most people who start GLP-1s for weight loss stop within a year. And when they stop, the weight tends to come back – often faster than it would after a non-drug weight-loss program, according to a recent University of Oxford analysis.
Researchers are now looking closely at whether that yo-yo cycle of losing and regaining is itself a risk factor for heart and metabolic problems. That’s the gap ENV-308 is aiming at: not replacing GLP-1s, but helping people hold onto the benefits after they stop taking them.
The Phase 1 trial enrolled 88 healthy volunteers, and the headline result was tolerability. Nausea and vomiting are the most common reasons people quit GLP-1 medications, and ENV-308 came through with what the company describes as an exceptional gastrointestinal safety profile – no serious side effects, no one dropping out because of how it made them feel.
The trial also tracked leptin, a hormone made by fat cells that tells your brain how much energy is stored on board. In obesity, leptin levels often run high while the brain quietly stops listening to the signal, a state researchers call leptin resistance. In this trial, ENV-308 lowered circulating leptin, with the biggest drops in people whose levels were highest to begin with, a signal that the drug is doing something real in the body’s energy-sensing system, not just passing through.
Enveda’s CEO, Viswa Colluru, put the bigger idea simply, saying that many of the benefits of exercise “can be traced back to chemical messengers that are released in the body.”
“ENV-308 is our attempt to put the chemistry of exercise into a daily tablet, and to offer a sustainable and convenient solution that synergizes with people’s daily habits and supports them on the path to long-term health,” he said.
One trial participant, a Massachusetts IT engineer in his 50s who’s been on GLP-1s for two years, described the trade-off many patients quietly live with.
“I’ve had to work hard to see the gains I have had on the GLP-1s, including putting up with the side effects and changing my lifestyle, but I’m worried about what will happen when I stop taking them,” the participant said.
What comes next, and why it’s worth watching
Because this first trial was run in healthy volunteers, it wasn’t designed to measure weight loss itself. That’s the job of the Phase 2 trial Enveda is planning next, specifically in people who’ve stopped or are planning to stop GLP-1 therapy.
Animal studies already hint at something promising: ENV-308 preserved lean muscle during weight loss and prevented rebound weight gain after treatment stopped, without the muscle loss that’s become one of the quieter concerns around GLP-1 use.
Weight loss alone was never really the goal for anyone serious about aging well. Losing lean muscle along with fat, then regaining it all in a yo-yo pattern, may do more long-term metabolic damage than staying at a stable, slightly higher weight. If a daily pill can help lock in the gains people fight hard for on GLP-1s, without the cycle of loss and regain, it’s not just a weight-loss story. It’s a shot at making metabolic health durable, decade over decade, which is the entire point of longevity medicine in the first place.