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
The Endocrine Society obesity statement: health comes first, not just the number on the scale
The new Endocrine Society obesity statement sketches out the future of obesity treatment. The society itself is the large international organization of physicians and researchers who specialize in hormones. Its central message is simple: we should measure treatment success in health, function and quality of life. In other words, the kilograms lost are only part of the picture.
The statement summarizes what we already know and which questions are still open. In addition, it defines the research that is still missing, so that doctors can match each person with the treatment that is right for them.
What the statement says, and who is behind it
The journal Endocrine Reviews published the scientific statement on September 9, 2026. Eight experts wrote it. According to the society’s announcement, Prof. Daniel Drucker of Mount Sinai Hospital in Toronto led the team. Drucker is one of the pioneers of research on the hormone GLP-1.
At the heart of the statement are the new medications, which build on hormones the gut releases in response to eating. They include semaglutide, the active ingredient in Wegovy and Ozempic. They also include tirzepatide, the active ingredient in Mounjaro. Today, these drugs allow some patients to lose 20% to 25% of their body weight. That is why it matters to understand what happens in the body during weight loss, and how to improve body composition and health.
Obesity is a biological disease, not a matter of willpower
Obesity is a chronic disease. Genetics, the brain, hormones, metabolism and the environment all influence it. According to the statement, the body actively regulates how much fat it stores, and where, throughout life.
The brain is the chief manager of this regulation. It decides how much fat to keep, and it uses hunger, fullness and energy expenditure to do so. Moreover, more than 75% of the genes linked to obesity are active mainly in the central nervous system.
When people lose weight by dieting alone, the body works to return to its previous weight. Appetite rises and energy expenditure falls. Scientists call this response metabolic adaptation. The researchers note that in humans, it stems mainly from increased appetite and less from a slower metabolism.
How the new medications change the picture
The new medications work differently. According to the model in the statement, they lower the fat target that the brain defends, so the body moves toward the new target. As a result, during the weight-loss phase, hunger, food cravings and food noise all decrease. Food noise means the intrusive, persistent thoughts about food.
Even so, the researchers admit that the mechanism is still not fully understood. It is not clear which brain cells are responsible for the benefit, and which for side effects such as nausea. If the two effects come from different cells, future drugs might not require gradual dose increases.
Why the same drug works differently in each person
Response to treatment varies widely between people. According to the statement, this variability looks similar across very different treatments: a low-carbohydrate diet, tirzepatide and gastric bypass surgery. In each of them, the standard deviation is 10% to 12% of body weight. Standard deviation is a statistical measure of how widely results spread around the average. Put simply, the differences between people are large with every treatment method.
However, genetic tests cannot currently predict who will respond to which drug. The goal for the future is precision medicine. That means identifying subtypes of obesity and developing markers that predict the response to each treatment. According to the statement, this is still an aspiration.
Endocrine Society obesity statement: measuring success in health
Today, regulators approve an obesity drug mainly based on average percentage weight loss. The researchers argue that in the era of powerful medications, this measure is no longer enough. The reason is simple: different organs and conditions respond to different degrees of weight loss.
- A loss of 2% to 5% can already improve blood sugar levels and lower triglycerides, a type of blood fat.
- With a loss of 5% to 10%, improvements in quality of life and physical function appear.
- A loss of 10% to 15% is usually necessary for a meaningful improvement in sleep apnea and knee osteoarthritis.
Body mass index (BMI) is also limited, because it does not measure the amount of fat or where it sits. Therefore, the statement recommends also looking at the waist-to-height ratio. It also recommends assessing body composition: fat, muscle and bone.
Treatment targets, as in any chronic disease
The vision is to set treatment targets. For example, in diabetes, doctors aim for a glycated hemoglobin (HbA1c) below 6.5%. Similarly, in obesity, it may become possible to aim for a target based on health outcomes. I expanded on this idea in my article on treat-to-target dosing with GLP-1 medications.
The statement cites an example from a study presented at the European Congress on Obesity in 2024, based on medical records from the UK. After weight loss, a BMI of 27 and/or a waist-to-height ratio of 0.53 or below went along with a low risk of type 2 diabetes, high blood pressure, joint osteoarthritis and atherosclerotic heart disease.
The Endocrine Society obesity statement: three phases of treatment
Accordingly, the statement proposes dividing drug treatment into physiological phases:
- The weight-loss phase: the drug lowers the brain’s fat target, and weight falls toward it. During this phase, appetite is especially low.
- The plateau phase: weight stops falling on a given dose. This is not a sign that the drug has stopped working, but rather a new balance.
- The maintenance phase: treatment holds that balance for years. Sometimes it needs adjusting, because obesity can progress over time.
Most studies to date lasted about a year to a year and a half. Consequently, they mainly describe the weight-loss phase. We know much less about the plateau and maintenance phases, and this is one of the gaps the statement seeks to close.
Endocrine Society obesity statement: does every patient need the maximum dose?
Today, doctors raise the dose up to the maximum tolerated dose, as in the clinical trials. According to the researchers, this approach is almost unique to obesity among chronic diseases. At times, it leads to intolerance and excessive weight loss. For this reason, they call for studies on the lowest effective dose, that is, raising the dose only until the patient reaches a health target.
Early data already support this direction. In the SURMOUNT-MAINTAIN trial, patients switched to tirzepatide 5 mg a week after the weight-loss phase. After 112 weeks, they were at a 16.6% loss from the start of the study, compared with 21.9% on the maximum dose and 9.9% on placebo. Meanwhile, in the ATTAIN-MAINTAIN trial, patients switched from injections to the daily pill orforglipron (Foundayo). Those who switched from tirzepatide kept 74.7% of their weight loss, and those who switched from semaglutide kept 79.3%.
On the other hand, stopping treatment usually leads to weight regain. Blood pressure, blood fats and blood sugar also rise again. According to the statement, this is what happens when people stop treatment for any chronic disease.
Benefits beyond weight: heart, sleep and liver
In recent years, these medications have also received approvals beyond obesity. In 2024, the FDA approved semaglutide to reduce major cardiovascular events, and tirzepatide for sleep apnea. A year later, in 2025, the FDA also approved semaglutide for metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis.
Heart: the SELECT trial enrolled 17,604 people with heart disease and overweight or obesity, but without diabetes. Over an average follow-up of 39.8 months, a major cardiac event occurred in 6.5% of those on the drug, compared with 8.0% in the placebo group. In addition, 16.6% stopped the drug because of side effects, compared with 8.2%. You can read more in my article on the SELECT trial and heart protection.
Sleep: the SURMOUNT-OSA trials enrolled 469 people with obesity and moderate to severe obstructive sleep apnea. Tirzepatide reduced the number of breathing pauses per hour of sleep, body weight and blood pressure.
Liver: in the ESSENCE trial, liver inflammation resolved without worsening of scarring in 62.9% of those on semaglutide, compared with 34.3% on placebo. According to the statement, a further analysis of the trial points to a liver benefit that does not depend on weight loss alone.
Muscle, bone and lifestyle
Large weight loss also includes a loss of lean tissue. The statement stresses that there is currently no agreement on the best way to measure muscle, fat and bone in the clinic. So it calls for developing low-cost, accurate tools. Also, in SELECT, researchers saw more hip and pelvic fractures among women over 75 who received the drug. I covered the practical side in my article on preserving muscle mass during weight loss.
The medications do not replace a healthy lifestyle. Instead, the statement calls for studies on how to combine drugs with nutrition and physical activity, both in the weight-loss phase and in the maintenance phase.
The Endocrine Society obesity statement on long-term safety
The most common side effects are gastrointestinal, such as nausea and vomiting. Because of them, doctors raise the dose gradually. In addition, rapid weight loss by any method raises the risk of gallstones. The statement also lists rare effects, such as ischemic damage to the optic nerve (NAION).
Use of these drugs is expanding and sometimes continues for years. Hence, the need for long-term safety data is growing. According to Drucker, the field needs large, long and diverse studies, as well as broad use of real-world data.
Bottom line: the Endocrine Society obesity statement
The statement makes it explicit that it is not intended to guide treatment. Instead, it defines what we know, where knowledge is missing and which studies will move the field forward. According to reports, the society plans to publish a clinical guideline on drug treatment for obesity in 2027.
The Endocrine Society obesity statement marks a shift from a focus on weight alone to treating a complex chronic disease. Today, the key question is no longer just “How much did you lose?” but “How much did your health, function and quality of life improve?” In the future, we will also measure success in less heart, liver and kidney disease, better sleep and preserved muscle and bone.
The information in this article is general and does not replace personal medical advice. Please make any dose change, switch between drugs or decision to stop treatment together with your treating physician.
References
Endocrine Society Scientific Statement provides research roadmap for what’s next in obesity science
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity
Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis
Scientific statement to researchers: Look at obesity outcomes beyond weight loss
