Losing weight only to gain it back later. Can weight-loss pills cure "weight rebound"?

Text | Hu Xiangyun

Editor | Hai Ruojing

"This time, it's the country that won't allow you to gain weight."

On March 10th, at the press conference on people's livelihood themes during the Two Sessions of the National People's Congress and the Chinese People's Political Consultative Conference, Lei Haichao, the director of the National Health Commission, emphasized the promotion of a three - year "Weight Management Year" campaign to reduce weight and control chronic diseases. Subsequently, Zhang Wenhong, a member of the National Committee of the Chinese People's Political Consultative Conference, jokingly pointed at a journalist and said, "People with a big belly like you are our main targets." After several rounds of heated discussions, "weight loss" directly topped the Weibo hot search list.

Amid the banter, "weight regain after weight loss" was frequently mentioned by netizens. A review study stated that if obese patients only achieve weight loss through lifestyle changes, most of them will regain about half of the weight they lost two years after successful weight loss. By the fifth year, the regained weight may exceed 80% of the weight they lost.

In the scientific community, this phenomenon is called "metabolic memory," which means that the body will "remember" your weight level and maintain it within a stable range.

To combat this evolved physiological instinct and resist weight regain, the weight - loss field has entered the "second half of the competition." Leading players such as Novo Nordisk and Eli Lilly, as well as many emerging pharmaceutical companies, are trying to solve the problems of "muscle loss" and "weight regain" during the weight - loss process by searching for new drug targets with novel mechanisms and improving the functions of existing products.

In the weight - loss field where "blockbusters" and "miracles" often emerge, semaglutide has already created a myth with annual sales of $28.3 billion. Where might the way out be to break through the dilemma of "weight regain" in the future?

What to do if you lose weight and then gain it back?

"Do you know what intestinal cleansing is?" Abby asked us.

"It involves mixing a vegetable oil with hot water and injecting it into the anus, and then using a set of massage techniques to tap the bladder meridian to help the body expel feces and lose weight. One course of treatment costs 800 yuan per month, but it ultimately leads to intestinal flora imbalance."

The seemingly unreliable intestinal cleansing is just one of the many weight - loss methods Abby has tried. Abby is just over 30 years old, 160 cm tall, and weighs 190 pounds. She has a ten - year weight - loss history. To lose weight and become more beautiful, she has persisted in long - distance running, taken many health supplements claiming to have weight - loss effects, and also obtained regular weight - loss prescriptions from the outpatient department of a professional third - grade class - A hospital.

After uncalculated efforts, Abby has lost weight by ten pounds at a time. At that time, "watching the numbers on the scale keep dropping every day gave a dreamy feeling." However, without exception, the final outcome of the story is that she gained the weight back.

"Weight regain" is a headache for many people trying to lose weight. On Xiaohongshu, overweight friends self - mockingly say that "weight loss is a lifelong task" and "the end of losing weight by starving is weight regain." Even in professional weight - loss clinics, weight regain is an unavoidable topic for doctors. It seems that various weight - loss methods are facing this dilemma, with the only difference being the degree of weight regain.

A doctor who has been engaged in weight - loss work for nearly 20 years explained that weight regain after weight loss is most likely because the previous effective weight - loss method was not scientific, resulting in excessive muscle loss. "For example, losing weight by dieting will most likely lead to weight regain."

At the end of 2024, a study published in the journal Nature also mentioned when explaining "why many people always regain weight after losing weight" that it is because human fat cells have a "memory" of obesity. The experience of obesity can cause changes in a person's epigenome, and epigenetic mechanisms are very important for the development, differentiation, and even identity maintenance of fat cells. Therefore, after gaining weight, the changes in the epigenome leave a long - term "imprint." Once the weight - loss actions (such as dieting, high - intensity exercise, or taking medications) change, it may lead to weight regain.

In other words, weight regain after weight loss may be related to our genes.

Externally, there is a wide variety of existing products for weight loss. For example, GLP - 1 weight - loss drugs represented by semaglutide and tirzepatide; in terms of medical devices, products that have attracted much attention in recent years include gastric balloons and gastric bypass stent systems; among health supplements, there is the "Supermodel Pill" launched by Bloomage Biotechnology in October last year.

However, these products basically achieve weight loss by increasing satiety and suppressing appetite. Therefore, after stopping the medication, the original suppression mechanism no longer exists, the appetite will gradually recover, and the weight may also rebound. In 2023, a study published in the Journal of the American Medical Association stated that among the subjects who stopped taking tirzepatide after 36 weeks, their weight increased by an average of 14% within the subsequent 52 weeks (about 1 year), while the subjects who continued to take the medication lost 5.5% of their weight.

In essence, these existing products are like plug - and - play wireless network cards. They can control weight by affecting the appetite of people trying to lose weight at the moment, but it is difficult to fundamentally solve the problem of metabolism, resulting in "weight loss" always cycling between success and failure.

Recently, the media outlet "Medical Community" conducted a survey. Among more than 300 doctors in China who had received obese patients recently, 70% of them believed that "easy weight regain after weight loss" was the most important issue to be addressed in the future diagnosis and treatment of obese patients. Based on their experience, more than half of the patients experienced weight regain after stopping the medication due to problems such as lifestyle habits and non - standardized medication use.

To combat "weight regain," rely on black technology or on oneself?

In the already - competitive weight - loss drug and device field, solving the problem of "weight regain after stopping medication" is one of the clear directions for pharmaceutical companies to upgrade their products and compete in the fierce market. Whether exploring new drug targets or designing drug combination methods, large - scale companies are still increasing their investment in the research and development of weight - loss black technology.

A person from a GLP - 1 new drug company introduced that the muscle mass of the human body directly affects the basal metabolic rate. Therefore, if weight loss through medication is accompanied by muscle loss, it may lead to a decrease in the basal metabolic rate, which in turn will exacerbate weight regain after stopping the medication. Therefore, in recent years, some companies focusing on the research and development of weight - loss drugs have been actively emphasizing the benefits of "weight loss and muscle gain" of their products during the clinical trial process.

For example, Alnylam, a well - known small - nucleic - acid pharmaceutical company in the United States, is developing an RNAi therapy that can be used in combination with semaglutide. Existing pre - clinical data show that this therapy can "reduce more fat while preserving muscle mass and reduce weight regain after stopping semaglutide."

Large companies with mature products have also made corresponding arrangements. As early as 2023, Eli Lilly spent $1.9 billion to acquire Versanis Bio, an innovative pharmaceutical company focusing on cardiovascular and metabolic diseases, and obtained a monoclonal antibody product targeting the activin type 2 receptor (ActRII). The potential function of this target is precisely to make fat "disappear" and increase muscle mass. In a phase 2 clinical trial for obese patients with type 2 diabetes, this product can cause patients to lose about 22% of their fat while increasing their fat - free body weight by 4.5%.

In addition, searching for new targets that are expected to surpass GLP - 1 and achieve "weight loss without rebound" has also become the goal of pharmaceutical companies in the competition.

The British company NodThera claims to have found a new idea for weight loss through anti - inflammation. Although the progress is still in the early stage, it has caught the attention of Novo Nordisk. In 2018, Novo Nordisk helped it raise nearly $100 million for product development, and in 2022, it directly spent $700 million to acquire a product pipeline of NodThera.

However, the path for new drugs from clinical trials to the market is long, and many people who need to lose weight do not necessarily need to take medications. In contrast, "controlling diet" and "exercising regularly" for regular weight loss are the suggestions of more doctors.

"Accurate assessment, scientific diet, and choosing appropriate exercise methods," the aforementioned weight - loss doctor believes that scientific weight loss can help the body enter a healthy and stable state. "First, eat regularly. Losing weight by dieting usually leads to weight regain. Second, ensure the intake of high - quality protein in the diet and maintain a balanced diet. Third, cooperate with resistance exercises to stimulate muscle growth and retention."

Through this method, "even if you don't gain muscle, you won't lose muscle," which helps to alleviate the problem of weight regain. "Rapid and repeated weight loss is likely to harm the body. It is more reasonable to directly carry out long - term weight management. For example, the treatment cycle for weight management I design for some patients can reach more than 20 months. The process involves investigating the causes of obesity, designing weight - loss strategies, such as combining medication, diet, and exercise, and long - term maintenance after successful weight loss," said the weight - loss doctor.

After trying many reliable and unreliable weight - loss methods, Abby also realized that the most important things in weight loss are actually "persistence" and "changing lifestyle."

"I can't lose weight from 190 pounds to 120 pounds by inertia. At 190 pounds, I might just want to overeat late at night after work. On the other side of the time axis, at 120 pounds, I must have different eating habits, work styles, and life rhythms. Perhaps only by 'erasing' a part of the 190 - pound self can I achieve change."