An experimental injection helped participants in a large study lose much more weight than with obesity drugs already available on the market, Eli Lilly, the product’s manufacturer, announced on Thursday (21).
Among the heaviest patients in the clinical trial, the results were comparable to those observed with bariatric surgery. bypass gastric, today the only really effective treatment for most cases of severe obesity.
The drug, called retatrutide, appears to be the most potent yet in a wave of injections and pills that are transforming the treatment of obesity — to the point that some participants in other studies report that they stopped using it because they felt they were losing too much weight.
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If the effect of the medicine does not diminish over time and if the results in practice reproduce what was seen in the clinical study, it could expand what is understood today as the potential of a drug for weight loss.
Eli Lilly released the findings in a press release. The results have not yet been peer reviewed or published in a scientific journal.
The drug’s potent effects, however, come at a cost. At higher doses, it often causes gastrointestinal side effects that are so bothersome that some patients give up treatment.
According to Eli Lilly, 11% of participants who received the highest dose dropped out of the study because of adverse effects — a higher proportion than that observed with less potent obesity drugs already available.
All of these drugs tend to cause nausea, vomiting, diarrhea and constipation, but, in general, serious conditions are rare.
Eli Lilly has not yet applied for regulatory approval, but the drug is already generating enormous interest.
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As reports about the good results of Lilly’s studies spread, some Americans started turning to the internet to buy “pirated” versions from China — which has worried doctors and researchers, alarmed by the fact that these patients are not being monitored and could suffer harm.
If approved, the retrofit will enter an increasingly competitive market. Still, some doctors believe that it can be especially useful for heavier patients, who need to lose more weight and are resistant to bariatric surgery.
The results released by Eli Lilly come from a randomized study with 2,339 obese or overweight people. Those who received the highest dose of the drug lost, on average, 70 pounds (about 32 kilograms), or 28 percent of their body weight, after 80 weeks of treatment, the company said.
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Among the heaviest participants, the loss was even greater. Patients with a body mass index (BMI) above 35 — a range considered moderate or severe obesity — were evaluated after two years.
During this period, those who took the highest dose lost, on average, 85 pounds (about 38.5 kilograms), or 30.3% of their body weight. For comparison, patients undergoing gastric bypass usually lose between 30% and 35% of their weight in two years.
Weight loss with retatrutide exceeds what is generally observed with the two most popular injections against obesity today: Zepbound, from Eli Lilly itself, and Wegovy, from Novo Nordisk.
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These medications help people lose about 20% of their body weight over a similar period of time. Oral versions provide a more modest loss, of 12% to 14% of weight.
For the 24 million Americans classified as severely obese — a BMI of at least 40 — this is not enough.
To reach a weight considered healthy, they need to lose 36 to 45 kilos, says endocrinologist and obesity specialist Carolyn Apovian, from Harvard Medical School.
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Bariatric surgery is often capable of producing this effect. But it has always been a difficult option to accept, and the emergence of effective anti-obesity medications has made the procedure even less attractive for many patients. Demand for bariatric surgery has been falling as the drugs gain popularity.
Eli Lilly is betting that retatrutide can offer an alternative for these very heavy patients — an audience that, in fact, was the initial target for the drug’s development.
The company’s scientific director, Daniel Skovronsky, says he imagined that the medicine would be more interesting precisely for those who need to lose large amounts of weight. But when analyzing the results, he realized that the appeal may be broader.
The unexpected happened at the lowest dose tested. More people taking a placebo dropped out of the study due to perceived side effects than those taking the active drug, says Skovronsky.
With this lower dose, participants lost about 19% of their body weight — a result similar to that of the maximum dose of Zepbound. However, the retrofit seemed to be surprisingly well tolerated.
Like Wegovy and Zepbound, retatrutide is administered by weekly injection, with a gradual increase in dose, which helps to reduce gastrointestinal effects.
The medicine is a type of “turbocharged GLP‑1”, belonging to the class of drugs that revolutionized the treatment of diabetes, obesity and other conditions.
It acts on three hormones related to the control of appetite, energy balance and metabolism: GLP‑1 (target of Wegovy and Zepbound), GIP (also target of Zepbound) and glucagon, a hormone that neither Wegovy nor Zepbound modulate.
It is still unclear to researchers why targeting these three hormones generates a greater effect than that obtained with medications that act on just one or two.
Endocrinologist Ania Jastreboff, an obesity expert at Yale and principal investigator of the study, says the results are “very impressive, without a doubt.”
But he emphasizes that obesity is a chronic disease and that, more important than the number of kilos lost, are “the effects on the person’s health throughout their life”.
For Eli Lilly, the return is an opportunity to continue surfing the wave of weight loss medicines. The company’s sales soared thanks to Zepbound, for obesity, and Mounjaro, for diabetes. Last year, the company became the first in the healthcare sector to reach a market value of US$1 trillion.
In 2024, Lilly sued the American regulatory agency (FDA), alleging that the agency improperly classified retatrutide as a traditional medicine, and not as a biological product. The dispute, still pending in court, revolves around a highly technical issue: how many amino acids the retatrutide molecule has in its chemical structure.
If the drug is reclassified as a biologic, it could mean billions of dollars more for Eli Lilly, as it would make it harder for competitors to enter and allow it to charge higher prices for longer than would be possible under the current classification.
c.2026 The New York Times Company
