Without sweating: Scientists have developed a "fitness pill" that makes the body react as if it were exercising

Will it be possible in the future to take in a pill some of the metabolic changes that occur in the body following physical activity? A new experimental drug, which has entered human trials for the first time, is trying to do exactly that. Although the initial results are very preliminary and do not prove that the drug causes weight loss, they provide a glimpse into one of the most intriguing approaches to developing the next generation of metabolic drugs.

Biotechnology company Enveda reported positive results from a Phase 1 trial of ENV-308, an experimental drug given as a daily pill and designed to mimic the activity of a substance the body produces in response to intense physical activity. So far, 88 healthy volunteers have participated in the trial, which was primarily intended to test safety, tolerability, and how the drug behaves in the body.

The long-term goal is particularly intriguing: to test if the drug could in the future help people maintain weight loss after stopping treatment with GLP-1 family drugs, such as Wegovy and Mounjaro.

What does our body produce during a workout?

At the center of the story is a substance called Lac-Phe. It is a molecule that has become a focus of research in the field of metabolism in recent years. It is created in the body, among other things, following intense physical activity and also after eating.

Studies in animals have shown that Lac-Phe is capable of suppressing appetite and reducing obesity, thereby suggesting a possible biological mechanism through which physical activity affects metabolism. The problem is that the natural molecule is cleared from the body quickly and therefore is not suitable as a drug on its own.

Researchers developed ENV-308 with the goal of mimicking the effects of Lac-Phe, but in the form of a molecule that can be taken daily in a pill. The drug was identified using an artificial intelligence-based system developed by the company to find biologically active molecules that exist in the body and in nature.

But it is important to emphasize: this is not a "fitness pill" — it does not replace physical activity, and it has not been proven to provide all the benefits of exercise.

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The first human trial

88 healthy adults participated in the Phase 1 trial. At this stage of drug development, researchers are not yet trying to prove that it causes weight loss or prevents obesity. The main goal is to check if the drug is safe, how the body reacts to it, and how it is absorbed and cleared.

According to data published by the company, the drug was well tolerated across all dose ranges tested. No serious adverse events, treatment discontinuations, or dose interruptions were reported. The researchers particularly emphasize the gastrointestinal tolerability profile.

This point is interesting against the backdrop of GLP-1 drugs, where nausea, vomiting, and other gastrointestinal phenomena can make treatment difficult for some patients.

However, it is very early to compare the treatments. ENV-308 was tested at this stage on healthy volunteers and in a relatively small study, so it is not yet known how it will behave in people with obesity or metabolic diseases and with prolonged use.

The hint that came from the satiety hormone

Alongside safety, researchers looked for initial signs that the drug indeed affects metabolic pathways. One of them came from a hormone called leptin.

Leptin is secreted by fat cells and transmits information to the brain about energy stores in the body. In people with obesity, leptin levels are sometimes chronically high, but the brain responds to it less, a condition known as leptin resistance.

In the trial, a decrease in leptin levels in the bloodstream was observed following treatment, with the largest decreases seen in participants whose leptin levels at the start of the study were higher relative to their gender. The company is planning further studies to clarify what the change means and whether it indeed indicates a metabolic effect with clinical significance.

The big goal: what happens after stopping GLP-1?

One of the biggest problems of the weight-loss drug era is maintaining the result. After stopping treatment, many patients regain weight, and some of the improvement in metabolic markers may disappear. Here, the developers hope to find a role for ENV-308.

In animal studies, the drug helped maintain weight loss after stopping weight-loss treatment and even preserve lean body mass during weight loss. Preclinical trials also raised the possibility of combining it with GLP-1 drugs. But all these findings still need to stand the test that really matters: humans.

The company is now planning a Phase 2 trial in which it will be tested whether ENV-308 is indeed capable of helping maintain weight and metabolic benefits in people who stop GLP-1 treatment. Only in the next studies will changes in weight, body composition, and other metabolic markers also be examined.

And this is also the most important caveat to the tempting headlines about "physical activity in a pill": in the current trial, it was not tested at all whether ENV-308 causes weight loss. The participants were healthy, and the study was designed to test safety, not efficacy. If the next studies are successful, the drug could represent a new approach: not to replace physical activity, but to use knowledge about the chemistry that the body itself produces as a result of it to develop a new metabolic treatment. At the current stage, this is an intriguing scientific possibility, not a therapeutic promise.