By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
New obesity treatment targets: a shift in thinking
New biological obesity treatment targets are changing the way researchers think about care. In the past, the main goal was weight loss alone. Today, research asks much deeper questions: how to preserve muscle, how to quiet food noise and how to prevent weight regain. At the European Congress on Obesity (ECO 2026), researchers presented a series of early developments that may shape the future of the field.
It is important to say this up front: researchers carried out most of these studies in cells and animals. So they point to a direction, not a treatment you can get. Even so, they teach us a lot about the disease itself. Obesity is a biological disease that involves the brain, muscle, liver, gut and fat cells.
Can you lose weight without losing muscle?
Drugs such as tirzepatide and semaglutide lead to impressive weight loss. However, part of that loss comes from lean body mass, not only from fat. For this reason, researchers are looking for ways to protect muscle during treatment. I have written about practical ways to do this in my article on preserving muscle during weight loss.
One intriguing direction is blocking a protein called USP19. This protein is active in muscle under stress and promotes its breakdown. In a study in mice lacking USP19, researchers found less fat and a high proportion of lean mass. In addition, these mice gained less weight on a high-fat diet and had better insulin sensitivity.
At the congress, presenters shared data on ALM-601, a pill that blocks USP19. According to the presenters, in obesity models, combining it with tirzepatide nearly doubled weight loss. Moreover, the loss came almost entirely from fat, while muscle mass and strength held steady. If these results hold up in humans, this could especially help older adults, patients after bariatric surgery and people with sarcopenia, the loss of muscle mass and strength.
Obesity treatment targets: amylin returns to the stage
In recent years, most of the attention has gone to GLP-1. At the congress, however, researchers also presented data on another family: drugs that mimic amylin. Amylin is a natural hormone that the pancreas releases together with insulin. It affects satiety, the pace of stomach emptying and metabolic balance.
Some drugs in this class, such as cagrilintide, act on both amylin receptors and calcitonin receptors. A preclinical study has already shown that the balance between these receptors affects the outcome. The study presented at the congress tested whether a selective amylin drug is better at preserving lean mass. Surprisingly, the researchers found no meaningful difference between the two approaches. On the other hand, they noted that activating calcitonin receptors may benefit bone health.
The olive as inspiration for a future drug
One of the most intriguing studies looked at elenolic acid, a natural compound from the olive. It forms when oleuropein breaks down as the fruit ripens. In a study published in 2022, the compound stimulated the release of GLP-1 and PYY, two satiety hormones from the gut.
Mice with obesity that received the compound for two weeks cut their food intake by about 21%. In addition, fasting blood sugar returned to normal, and body fat percentage dropped. At the congress, researchers also reported improvement in fatty liver, and an effect similar in some measures to that of liraglutide. Still, this is a very early stage. Olive oil or a supplement is no substitute for treatment.
Can we prevent weight regain? New obesity treatment targets in fat cells
Weight regain after stopping medication is one of the field’s central problems. Here, presenters offered a novel idea: not just shrinking fat cells, but causing them to undergo apoptosis, or programmed cell death.
Its developer originally designed the compound CBL-514 to reduce localized fat. According to the company, it works through the DYRK1B pathway. Data presented at the EASD meeting in September 2026 showed a reduction in deep abdominal fat in small phase 2 trials. Furthermore, in rats that received the compound together with tirzepatide, weight regain after stopping treatment was much smaller. The hypothesis is simple. If the number of fat cells is smaller, the body has a harder time rebuilding its fat mass.
The microbiome, gut bacteria and metformin
Doctors have used metformin to treat diabetes for decades. Now, studies are revealing surprising ways it works in the gut. At the congress, researchers presented work showing that the drug changes not only the makeup of the bacteria, but also their behavior. Specifically, it reduces how far bacteria penetrate the gut’s mucus layer.
This finding connects to an earlier lab study in which E. coli bacteria sensed metformin as a repellent and moved away from it. The drug also slowed the bacteria’s movement. Together, these findings strengthen the understanding that obesity and diabetes also involve the gut, the immune system and the microbiome.
The brain, food noise and computer models
Another fascinating area is computer modeling of how semaglutide acts in the body and brain. Researchers at Eindhoven University of Technology built a simulation that combines digestion, metabolism and the brain. According to the model, the drug weakens the dopamine response to eating. In other words, each meal is less rewarding, and the urge to keep eating drops.
According to the model presented at the congress, the drop in reward-system activity appears early, even before satiety peaks. This may explain why many patients report fewer intrusive thoughts about food, or “food noise,” even before major weight loss. In the future, we may tailor treatment to a brain, metabolic and behavioral profile, not just to BMI.
What do these obesity treatment targets mean for you?
These new obesity treatment targets are not drugs you can get today. Most will take years to reach large human trials, and some will never get there. Therefore, the right treatment today relies on proven tools: effective medications, a protein-rich diet, strength training and close medical follow-up.
At the same time, the trend is clear. The next generation of treatments aims for high-quality weight loss, with less muscle loss, less hunger and less regain. It also aims for good metabolic health and function that lasts for years. If you would like to discuss which options fit you today, you are welcome to contact my clinic.
The bottom line on obesity treatment targets
The main message from these studies is that obesity is not just a matter of excess calories. It is a biological disease that involves the brain, muscle, liver, immune system, microbiome and fat cells. New obesity treatment targets let us see the disease in all its complexity. Ultimately, we will not measure the future of obesity medicine only in kilograms. Instead, we will measure it by our ability to live healthy, active, full lives for years to come.
The information in this article is general and does not replace personal medical advice.
References
CBL-514 injection reduces visceral and subcutaneous fat in trials
Metformin Alters the Chemotaxis and Flagellar Motility of Escherichia coli
