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"In the past 40 years, the prevalence of obesity in China has increased nearly 10 times. Obesity is the source of all chronic diseases. If obesity is controlled, downstream diseases can be well prevented and treated."

"Improving lifestyle can generally reduce 5%-10% of body weight, and metabolic surgery can generally reduce 25%-30% of body weight. New weight loss drugs can reduce weight by 15%-20%, and some patients can even lose more. But it is impossible to lose weight once and for all with drugs alone. Drugs are just an auxiliary."

On July 19, 2024, Eli Lilly (LLY.US), a multinational pharmaceutical company, announced that the weight-loss version of telportipadine was approved for marketing by the China National Medical Products Administration (NMPA) (trade name: Mufengda), just three weeks after the weight-loss version of semaglutide, which has become popular all over the world as a "weight-loss drug", was launched in China (trade name: Novowin). Both drugs are used for long-term weight management, that is, they are used on the basis of adjusting diet and increasing exercise.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that can activate the GLP-1 receptor, while tepoxetine is a glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist that can activate both the GIP receptor and the GLP-1 receptor. Both reduce food intake, weight, and fat mass by regulating appetite.

A report released by consulting firm IQVIA on February 22, 2024 believes that the arrival of GLP-1 receptor agonists, especially Wegovy (semaglutide injection), marks a turning point in the obesity market as drug intervention achieves meaningful weight loss of 10%-15% for the first time.

Obesity is a big market. According to the IQVIA Institute's 2024 Global Drug Use Report, global obesity spending reached nearly $24 billion in 2023, an increase of more than seven times in just three years. Starting in 2024, the market is expected to accelerate rapidly, reaching a potential value of $131 billion by 2028.

The weight-loss version of semaglutide was launched in the United States as early as June 2021 (trade name: Wegovy), and quickly entered the public eye with the "endorsement" of celebrities such as Tesla CEO Elon Musk (Elon Mask). In 2023, Wegovy's sales were approximately US$4.53 billion, a year-on-year increase of 407%.

Although semaglutide has the momentum to impact the "global drug king", Eli Lilly's tepote is still attracting much attention and is considered to have the opportunity to compete with semaglutide for the throne of the weight loss market because of its impressive data-in multiple clinical trials, the weight loss effect has repeatedly set records. In November 2023, the U.S. Food and Drug Administration (FDA) approved the weight loss version of tepote for marketing (trade name: Zepbound). According to Eli Lilly's 2023 financial report, Zepbound's sales reached US$176 million in less than two months after approval. In the United States, Zepbound is priced at US$1,059.87 per month, which is about 20% lower than Wegovy's price of US$1,350 per month.

There are many pharmaceutical companies that want to get a piece of the $100 billion market. It is reported that there are more than 200 GLP-1 receptor agonists in the world that are in the preclinical to approval stage. According to Endpoints News, a biopharmaceutical industry media, Jim Miller, a biomanufacturing consultant, believes that it may take about three years for the next competitor of Novo Nordisk and Eli Lilly to enter the market. In addition to injections, oral versions of GLP-1 drugs are also on the way.

Obesity has become a global public health issue. In March 2024, the World Obesity Federation released the World Obesity Atlas 2023, which predicts that by 2035, more than 4 billion people will be obese or overweight, accounting for 51% of the world's population. The 2022 edition of the Chinese Dietary Guidelines shows that the proportion of overweight and obese adults in China has exceeded 50%.

What exactly is "obesity"? Is it a disease? How much impact will the launch of new weight loss drugs have on weight loss treatment? On July 31, Professor Li Xiaoying, Director of the Department of Endocrinology at Zhongshan Hospital Affiliated to Fudan University (hereinafter referred to as "Zhongshan Hospital"), accepted an exclusive interview with The Paper. He is also the principal investigator of the clinical trial (SURMOUNT-CN) conducted by Mu Fengda in China. In 2023, he and Professor Ji Linong of Peking University People's Hospital jointly led the establishment of the Endocrinology and Metabolism Obesity Diagnosis and Treatment Alliance, aiming to establish a multidisciplinary obesity diagnosis and treatment team with endocrinology as the main department, and convey the concept of healthy weight management to the society.

Li Xiaoying said that the new GLP-1 type weight loss drugs may become the main treatment for obesity in the future, but it is impossible to rely on drugs to lose weight once and for all, and drugs are only a supplement. Such drugs may continue to be in short supply in the future, and the reason why they are so popular is that more people use them for aesthetic reasons rather than for treatment.

The fifth person on the left is Dr. Li Xiaoying. Photo provided by the interviewee

【dialogue】

What is considered obese?

The Paper: As a doctor, what do you understand by obesity?

Li Xiaoying (Director of the Department of Endocrinology, Zhongshan Hospital, Fudan University)：When ordinary people talk about obesity, they mean that the weight exceeds the normal range. Currently, the most commonly used indicator for measuring weight is BMI (body mass index), which is calculated by dividing weight (kg) by height (m) squared. BMI is commonly used because it is relatively easy to obtain and only requires measuring height and weight.

In the West, BMI ≥ 30kg/㎡ is considered obese. Data from Chinese people show that when BMI ≥ 28kg/㎡, the risk of hypertension, diabetes, cardiovascular disease, etc. will increase significantly, so China's obesity standard is BMI ≥ 28kg/㎡. Overweight is a weight between normal and obese. In the West, BMI of 25-30kg/㎡ is considered overweight, and China's overweight standard is BMI of 24-28kg/㎡. Although this method of judging obesity is convenient and simple, more and more people believe that it has some shortcomings and defects in recent years.

What is obesity objectively? In addition to the indicator of weight, the weight of body fat (body fat) is more important. Many athletes are very heavy and look fat, but they have muscles and a low body fat percentage. The body fat of normal men is about 15%-20% of body weight, and that of women is 20%-25%. Exceeding this range is considered obese. Currently, the simplest way to measure body fat is bioimpedance. Fat has different electrical conductivities from other components (different resistance to signal transmission). The approximate proportion of fat can be measured through the bioimpedance method. There are also more accurate methods such as dual-energy x-ray (DEXA). Compared with weight, the acquisition of the body fat indicator is more complicated.

We recommend that if your BMI is overweight or obese, it is necessary to further check your body fat, which may help with subsequent treatment.Generally speaking, BMI and body fat are proportional, and only a small number of people have inconsistent indicators., the doctor needs to analyze how much body fat is in excess before deciding on future treatment.

Another indicator is waist circumference. If the fat is evenly distributed and is under the skin, it is actually some fat that is not harmful. If the fat is in the abdomen, it is medically called increased intra-abdominal fat and increased abdominal circumference, which is central obesity and is more harmful. This is because abdominal fat can produce very bad factors, leading to an increased risk of some diseases. For Chinese men with a waist circumference of ≥90cm and women with a waist circumference of ≥85cm, it means they are centrally obese, and the risk is greater than that of BMI, which is considered overweight/obese.

The Paper: According to the "Dietary Guidelines for Chinese Residents (2022)" released by the Chinese Nutrition Society, the overweight and obesity rate of adult residents in my country has exceeded 50%. On June 26, 2024, the National Health Commission specifically discussed the issue of weight management at a press conference and mentioned the launch of the "Weight Management Year" campaign. How serious is China's obesity problem?

Li Xiaoying: According to epidemiological data, about 14% of people in China are obese and 36% are overweight, but China's population base is very large.Over the past 40 years, the prevalence of obesity in China has increased nearly tenfold.According to the "China Obesity Prevalence Map" ("China Obesity Prevalence and Related Complications: A Cross-sectional Real-World Study of 15.8 Million Adults", published in the academic journal "Diabetes, Obesity and Metabolism" in November 2023), obesity/overweight problems in China are more common among men than women; the obesity/overweight rate in the northern region is higher than that in the southern region, higher in the northeast and northwest, and lower in Guangdong and Fujian; in terms of age, obesity is becoming younger, and the proportion of obesity in children and adolescents is increasing. In the past, there were not many obese patients seen in hospitals because there were no effective drugs. After the emergence of new weight-loss drugs, more and more obese patients come to the hospital.

The Paper: Why do people get fat?

Li Xiaoying：First of all, life is getting better and better. Weight, especially the increase in body fat, is related to energy storage. When the energy intake is greater than the energy consumed, weight will increase. The energy intake is relatively easy to calculate, and the energy consumed is divided into several aspects: physical activity consumption accounts for about 30%, daily consumption (such as eating itself requires energy consumption) accounts for about 10%, and the remaining 60% is basal metabolism, that is, the minimum energy consumption required for the human body to maintain life activities in a quiet state. Our lives have changed dramatically in the past 40 years. The Chinese people's carbohydrate intake has decreased, but the intake of calories and fat has increased. On the other hand, our activities have decreased, more people work indoors, and most people choose to drive, take the subway, or ride an electric car to travel, and very few people walk or ride a bicycle.Lifestyle is the primary influencing factor of obesity, and the other is genetic factors.

New GLP-1 anti-obesity drugs are changing weight loss treatment

The Paper: How are GLP-1 drugs used clinically?

Li Xiaoying: In the past, a series of GLP-1 drugs were all indicated for diabetes. They have very good blood sugar lowering effects, but the weight loss effects are not that good. This is because these drugs were developed for diabetic patients at the time.For example, the maximum dose of semaglutide used in hospitals in the past was 1.0 mg, which is the dose that has a blood sugar-lowering effect. Although it has shown a weight loss effect in some diabetic patients, it is not a dose for weight loss.In June this year, the 2.4mg weight-loss version of semaglutide was launched in China. On July 19, Eli Lilly's Mufengda was launched in China. They are the real GLP-1 drugs for weight loss.

The Paper: Will they change the landscape of clinical weight loss treatment?

Li Xiaoying: Definitely. The main means of treating obesity clinically now are to improve lifestyle, i.e. control diet and increase exercise, and metabolic surgery. There are many other therapies, but the actual weight loss is limited.Improving lifestyle can generally reduce 5%-10% of body weight, and metabolic surgery can generally reduce 25%-30% of body weight. Metabolic surgery is surgery after all, and the number of people who use it is limited. The new weight loss drugs can reduce weight by 15%-20%, and some patients can even lose more. The original weight loss drugs can reduce about 7%-10% of body weight, which is similar to the effect of improving lifestyle. Therefore, strong and effective weight loss drugs should become the main treatment for obesity in the future.

This means that more patients will come to the hospital in the future, because whether buying in the hospital or in the pharmacy, a hospital prescription is required. This brings up another question, which department of doctors should be found to prescribe medicine? It must be the endocrinology department, because the endocrinology department is most familiar with obesity and its complications, and GLP-1 drugs. Therefore, in the future, weight loss treatment will be led by the endocrinology department, with doctors, nutritionists, and health managers participating together.

We are now entering a transitional period for obesity management. The National Health Commission has proposed launching a "Weight Management Year" campaign, which shows that obesity is taken very seriously. The number of chronic diseases has increased too much in recent years. The so-called chronic diseases are diabetes, hypertension, cardiovascular disease, tumors, fatty liver, etc.Obesity is the root cause of all chronic diseases. If obesity is controlled, downstream diseases can be well prevented and treated.Under this premise, Zhongshan Hospital took the lead in establishing the Endocrinology and Metabolism Obesity Diagnosis and Treatment Alliance, and united the endocrinology departments of hundreds of hospitals in China to promote the extensive construction of weight loss clinics and standardize the diagnosis and treatment of obesity in medical institutions, including intervention methods, follow-up, etc. Now 32 hospitals have joined the alliance, and there will be 100 by the end of this year, and there may be 300 next year, and it will gradually expand.

The Paper: Both NovoInc and Mufengda prescribe medications based on BMI. As mentioned earlier, BMI is not a perfect indicator. Do doctors need to do more assessments on patients when prescribing medications?

Li Xiaoying: When prescribing medication to patients, BMI is the first consideration. We also use medical history and laboratory tests to determine whether the patient has comorbidities. Doctors also need to determine whether the patient's BMI and body fat are consistent. If they are consistent, body fat measurement is not necessary when prescribing, but rather supplementary. We recommend that weight loss clinics opened by the Department of Endocrinology include body fat measurement, because hospital specialists should be more standardized than social institutions.

The Paper: Now many online pharmacies can also prescribe this type of medicine.

Li Xiaoying：This type of medicine requires a prescription. If a patient goes to a pharmacy to buy medicine without seeing a doctor, there is a certain risk. If a person's BMI is normal or even below the standard, and he/she still goes to the pharmacy to buy medicine to lose weight, the pharmacy does not know whether he/she is fat or thin, and gives him/her medicine, which will further aggravate his/her weight loss and cause him/her anorexia.

On the other hand, this type of drug may cause serious gastrointestinal reactions. Some people may experience nausea, vomiting, and diarrhea, but the patient may not know this. Therefore, the use of this type of drug requires the doctor's judgment. The doctor should explain to the patient the possible side effects and many issues that need to be paid attention to during the medication process. For example, this type of drug should be injected at a small dose and gradually increased. Some patients are not aware of this and take the maximum dose at once, which can cause very serious side effects.

There is no one-size-fits-all way to lose weight

The Paper: GLP-1 drugs are very popular now, and everyone thinks they are "magic drugs for weight loss." Is there a "magic drug" for weight loss?

Li Xiaoying: It is not a miracle drug, that is a bit exaggerated.In the nearly 100-year history of weight loss drug research and development, there has indeed never been a weight loss drug as effective as today's drugs.I can't say it's a miracle drug, but for obese people, I think it has a "magical" effect - it has a good weight loss effect, relatively speaking, no particularly serious side effects, and currently it's safe. It's not clear exactly where it works and what the specific principle is, so there's a sense of mystery. It's not a permanent way to lose weight, and once you stop taking it, you'll rebound. So patients who use this type of drug must combine diet and exercise control to maintain the weight loss effect, especially during the drug withdrawal phase.It is impossible to lose weight once and for all by relying on medication alone. Medication is only an auxiliary.

The Paper: GLP-1 drugs, represented by semaglutide, are so popular around the world that they are in short supply. In the past, some unscientific weight loss methods have also been popular, such as drugs for clearing the intestines and removing stool, liposuction for weight loss, and there are many promotional information on the Internet similar to 7-day fast weight loss. Why can these unscientific weight loss methods be popular for a long time? Is the reason behind these phenomena that people have too strong an aesthetic awareness of the body?

Li Xiaoying: In the past, drugs officially approved by the Food and Drug Administration could not achieve rapid weight loss. Those so-called rapid weight loss drugs were based on these drugs and added some other ingredients. Strict dietary control can help you lose weight quickly, such as the ketogenic diet, where the daily carbohydrate intake accounts for less than 10% of the total energy intake, but it is unlikely to be sustainable and long-term use may not be beneficial to health. Medically, rapid weight loss is not accepted. Usually, losing one kilogram a week is enough, becauseRapid weight loss not only reduces fat, but also muscles.

Semaglutide is popular, but many people cannot get the drug because many people use it from an aesthetic perspective rather than from a disease treatment perspective.Obesity was not considered a disease for a long time, and the World Health Organization officially defined it as a disease in 1997.In real life, if a person's BMI reaches the standard of obesity, but his blood pressure, blood lipids, and blood sugar are all normal, and he can eat, drink, and sleep, is this a disease? If it is not a disease, why should he be treated? Because although these indicators are normal, this person is actually facing extremely high health risks.

Obesity is usually classified clinically. Those with at least one abnormal metabolic indicator are classified as pre-obesity, but not clinical obesity. Clinical obesity definitely needs treatment, while pre-obesity requires preventive treatment. According to the principle of supply and demand, drugs should first be provided to obese patients with comorbidities, followed by obese people with disease risks, and finally to people with aesthetic needs. However, the number of such people is large, which occupies resources.

The Paper: Previously, there was a shortage of semaglutide and telportide both at home and abroad, and Novo Nordisk and Eli Lilly have been expanding their production capacity. Has the domestic shortage situation been alleviated? What are your concerns or hopes for the future clinical application of GLP-1 drugs?

Li Xiaoying: Currently, Novowin and Mufengda have been approved for marketing in China, but they are not yet available in the Chinese market, so there is no shortage. Previously, semaglutide, which was used to lower blood sugar, was sometimes available for diabetic patients. In the future, weight loss versions of the drug may also face shortages because they are produced abroad, and the demand for weight loss is too great, but the production capacity is limited.

In the future, when they are truly applied in clinical practice,First, we hope that patients who need these drugs most can get them. In addition, this type of drug has not yet been included in the medical insurance. If the drugs used by those who need them the most are included in the medical insurance, their problems can be solved. This type of drug is relatively expensive. Some people who are in urgent need of the drug may not be able to afford it, while some people who do not need the drug so much are using it. This situation may continue to exist in the future. In addition,This type of medicine should be prescribed by a doctor and should not be easily prescribed in pharmacies or medical beauty institutions.