For millions of people battling obesity, medications like Ozempic, Wegovy, and Trulicity have delivered hope. However, this hope often lasts only as long as the injections continue. Once the drugs stop, many patients see the pounds return. A new treatment could alter that cycle by addressing weight loss at its source, researchers say.
At this year’s European Association for the Study of Diabetes meeting in Vienna, scientists from Resalis Therapeutics presented early findings. The company is a biotech firm in Turin, Italy. Their first-in-class drug candidate, RES-010, targets metabolism itself. Unlike GLP-1 receptor agonists, which suppress appetite and slow digestion, RES-010 works differently.
“RES-010 works by reprogramming how cells handle fat and energy,” said Riccardo Panella, co-founder and CEO of Resalis. “Instead of reducing appetite, it changes the way in which the body uses fats. It boosts the production and activity of mitochondria, the ‘batteries’ that power cells. It also helps convert white fat, which stores energy, into brown fat, which burns it.”
A Different Approach
Ozempic and other GLP-1 drugs mimic a natural hormone that triggers a sense of fullness. Once patients stop using them, the hormone effect fades. This often leads to weight regain. A 2022 study in Diabetes, Obesity and Metabolism found that people who discontinued semaglutide regained two-thirds of the weight they had lost within a year.
RES-010 is different. It is an antisense oligonucleotide: a synthetic genetic strand designed to block a molecule known as miR-22. Scientists believe miR-22 acts as a master controller of obesity-related processes. These include fat metabolism, mitochondrial regulation, and the storage and remodeling of fat tissue.
In animal trials, mice given weekly injections of RES-010 for five months lost 12% more weight than untreated mice. Both groups ate the same number of calories. In non-human primates (monkeys and related species), the drug reduced fat mass (body fat) by 15% with only a 1% loss in lean mass (muscle and bone). By comparison, primates on semaglutide lost a similar amount of fat but also lost 8% of their muscle and bone tissue.
Maintaining lean mass, especially skeletal muscle, supports strength, stamina, and blood sugar management. Loss of lean mass can be detrimental.
Durability of Weight Loss
Perhaps most striking was what happened after the drugs were stopped. Animals given semaglutide alone regained the weight they had lost once treatment ended. But when semaglutide was paired with RES-010, weight loss remained stable — even after both medications were discontinued.
That finding suggests RES-010 may address a major criticism of the current generation of weight-loss drugs. These drugs often cause weight to rebound. By targeting metabolic pathways instead of appetite, scientists believe the drug could help patients achieve more durable results.
Clinical Trials Underway
RES-010 entered Phase 1 human trials in the Netherlands in November 2024. Results are expected in early 2026. While the study is still in its early stages, Resalis remains optimistic about its potential. “Because it acts on fundamental pathways, weight regain is less likely,” Panella said.
Still, experts caution that animal studies do not always translate to humans. “The idea of preserving lean mass while reducing fat is very appealing. But until we see long-term human data, we won’t know if the benefits hold up,” said Dr. Ania Jastreboff, an obesity medicine specialist at Yale School of Medicine, who was not involved in the study.
Editorial Perspective
The emergence of RES-010 highlights a turning point in the fight against obesity. The rapid adoption of GLP-1 drugs has demonstrated that medical treatments can significantly impact the landscape of weight loss. But their limitations are now equally clear. If RES-010 or similar therapies prove successful, discussions around obesity may shift from short-term appetite suppression to long-term metabolic reprogramming.
The outlook is currently cautiously optimistic. While GLP-1s have significantly impacted obesity care, new approaches may ultimately enable not only weight loss but also longer-lasting results for patients.
