Are you really happy if you lose weight with the miracle weight loss pill?

· "I used to be a 'foodie', but now I spend money to buy the things I like to eat, but after seeing them, I feel very annoyed and can't even eat a bite. I get very anxious and feel that I might as well not eat less."

"There are concerns that the presence of these drugs will exacerbate eating disorders and weight shame. It's a world where body anxiety is pervasive and what we need to do is better understand the relationship between health and weight."

After the injection, eating began to become a painful thing.

A young girl walked into the outpatient clinic, sat down and said, "I want semaglutide, please give me one." In the outpatient clinic of Chen Haibing, chief physician of the Department of Endocrinology and Metabolism of the Tenth People's Hospital of Tongji University, such scenes are not uncommon, " Many people just look a little fat, so they don't necessarily need to use semaglutide to lose weight." Chen Haibing said with a helpless smile.

In June 2021, the U.S. Food and Drug Administration (FDA) approved the second-generation glucagon-like peptide-1 receptor agonist (GLP-1RA) developed by the Danish multinational pharmaceutical company Novo Nordisk (NVO.US) Semaglutide (trade name: Wegovy) is indicated for long-term weight management in adults who are obese or overweight with at least one comorbidity. Since then, social media celebrities such as billionaire Musk have also stepped in to "bring goods", and semaglutide has quickly entered the public eye as a "miracle drug for weight loss."

There are also studies proving that semaglutide can reduce the risk of major adverse cardiovascular events, reduce symptoms related to heart failure, and treat non-alcoholic steatohepatitis, etc., adding another edge to the "miracle drug for weight loss".

Novo Nordisk's financial report for the first half of 2023 shows that the sales of its semaglutide products totaled 62.166 billion Danish kroner (equivalent to approximately RMB 64.4 billion), accounting for "half" of total revenue.

Under the leadership of semaglutide, the GLP-1 drug market has a bright future. Debon Securities predicts that the global market size of GLP-1 drugs in the field of type 2 diabetes and obesity will reach US$90 billion in 2030, of which the type 2 diabetes drug market accounts for approximately US$35 billion to US$40 billion, and the weight loss drug market accounts for approximately US$500 billion. billion to US$55 billion.

Capital's enthusiasm has successfully ignited consumers' dreams of "slimming down", but in actual use, "semaglutide" faces many restrictions.

Significant weight loss

Xu Qing, a 23-year-old girl from Chengdu, purchased "Nuoheli" online to lose weight. On JD.com, she chose an officially certified store. As long as she told the prescribing doctor during the online consultation that it was used for weight loss and proved that her body mass index (BMI) was higher than 25, she could buy it for 135 yuan. Xu Qing does not go to the hospital for outpatient consultation because she is a practitioner in the medical industry. "She deals with hospitals every day and is already half a doctor."

"Victoza" is Novo Nordisk's first-generation GLP-1RA - Liraglutide. It is a daily preparation and was approved by the FDA in 2010 for the treatment of type 2 diabetes. The overseas trade name is Victoza, in 2011 Entered the Chinese market in 2016. Another higher-dose version of liraglutide, Saxenda, is the world's first GLP-1RA approved for weight loss. It was approved for marketing by the FDA and the European Food and Drug Administration (EMA) in 2014 and 2015 respectively, but Its weight loss indication has not yet been approved in China.

Xu Qing is 1.6 meters tall and weighed 150 pounds at her heaviest. Since October last year, she has set a weight loss period for herself, hoping to lose 40 pounds by October this year.

At the beginning, she adopted a diet and exercise strategy: eating half a steamed bun for breakfast, vegetables and some high-quality protein for lunch, and not eating a bite at night. When she comes home from get off work, she will go to the gym to take classes, feeling exhausted. She has taken up to 20 classes in a month. After two months of this, I lost 30 pounds. But then the strategy stopped working.

This year, after her weight reached 134 pounds, she started taking liraglutide in early July. In just one month, her weight returned to 119 pounds.

28-year-old Shen Ping also used liraglutide and lost more than ten kilograms in a month. But one needle a day was too painful for him, and he only lasted three months. Shen Ping works in the media industry and is sometimes so busy that he forgets to take injections. Since he often travels on business, it is troublesome to carry it with him. Liraglutide needs to be kept refrigerated, so he bought a small portable refrigerator for this purpose.

Shen Ping is 1.78 meters tall and weighed nearly 300 kilograms at his peak. In the first half of 2022, Shen Ping suffered from obesity at work and was determined to put into practice the "weight loss" he often talked about. At that time, he happened to meet an endocrinologist and learned that there was a drug called semaglutide that only required one injection per week and had significant weight loss effects. He immediately became interested.

Novo Nordisk has three semaglutide products, namely Ozempic, a hypoglycemic injection for the treatment of type 2 diabetes, Wegovy, an injection for the treatment of type 2 diabetes and weight loss, and Wegovy, an injection for type 2 diabetes and is expanding into weight loss. Rybelsus, an oral tablet for severe indications. Currently, only Ozempic has been approved for import and marketing in China, with the trade name "Novota".

Shen Ping has been suffering from hyperinsulinemia for seven or eight years and takes metformin to maintain blood sugar balance. Hyperinsulinemia, in which insulin levels in the blood are above the normal range, is a major cause of the disease. Insulin resistance is a major cause of the disease. Insulin resistance refers to the reduced ability of insulin, the hormone that regulates blood sugar levels, to cause blood sugar imbalance and lead to type 2 diabetes. In June 2022, he was prescribed semaglutide through his medical insurance. A small size (1.5ml: 2.01mg) tube costs about 500 yuan, and a large size (3ml: 4.02mg) tube costs more than 800 yuan.

Taking 1 mg of semaglutide every week and combining it with 2-3 times of strength training, Shen Ping's weight has now dropped to about 250 kilograms, and his goal is to control it to less than 200 kilograms.

"Film and television migrant worker" Zhao Yun is 28 years old. He suffered from type 2 diabetes early and started taking semaglutide on the advice of his doctor. Zhao Yun was on a business trip for a long time, and his work and rest were reversed. Once he got busy, he couldn't even think about eating all day long. Three years ago, she was diagnosed with insulin resistance and weighed 130 pounds at the time. Zhao Yun is less than 1.6 meters tall. When she first graduated, she weighed only 92 pounds.

After taking metformin and pioglitazone, her weight quickly dropped to 108 pounds. After maintaining it for a period of time, she stopped pioglitazone on the advice of her doctor, but still needed to take metformin. Because she was too busy at work, she neglected to take medicine for a while, causing her weight to return to 120 pounds. In early July this year, she went to the Bariatric Department of Peking University First Affiliated Hospital for an examination and was diagnosed with type 2 diabetes.

The doctor told her that she was in the early stages of diabetes, and although it was not guaranteed to be reversible, she could use semaglutide to lower her blood sugar and take metformin as daily maintenance in the future. The first thing to do is to lose weight, with the goal of being under 100 pounds. The doctor explained: "By reducing to a relatively reasonable weight, you can reach a more appropriate BMI, and your blood sugar may be stabilized."

In an interview with The Paper, Zhao Yung had just finished three injections of semaglutide and his weight had dropped to 113 pounds.

Can you lose weight by lying down?

After the injection, Shen Ping felt that his appetite had dropped significantly, and he especially hated greasy food. He used to like fried chicken, but now he feels disgusted when he smells fried food. "I feel like it has a smell and I can't stand it." He used to like to eat fried chicken. Make an appointment with a friend for afternoon tea, order a cup of coffee and eat a piece of cake. Now he stays away from cake.

Shen Ping has been using semaglutide for more than a year. He feels that he has gradually entered a state where he doesn't want to eat. "This shows that the weight loss effect has been achieved." He said.

However, the efficacy of semaglutide will gradually weaken. After observing his condition, Shen Ping found that one injection of semaglutide was effective for about 5 days, and on the 7th day, he needed another injection.

"After taking the medicine for half a year, I obviously felt that my weight loss was getting slower and slower." Shen Ping remembered that at the beginning of the injection, he could lose four or five kilograms a week, but later he could only lose one or two kilograms a week. During this period, he also regained weight. When he returned home during the Spring Festival, he ignored his words and gained 10 pounds even though he took injections on time.

"I am now considering continuing to take injections. By the second half of this year, the oral version of semaglutide may be on the market. I will give it a try then," Shen Ping said.

Xu Qing takes an injection of liraglutide every day before going to work. She is full after taking a sip of water when she goes out in the morning. "I can sit still for the whole day, and I am not greedy until I get home from get off work. I have completely lost interest in eating."

Seems like losing weight is easy? She didn't think so. At first, she had severe gastrointestinal reactions: vomiting, bloating, burping, diarrhea, and not wanting to eat a meal for two days. After a period of time, she gradually adapted to it, but eating was still a painful thing: after the effect of the medicine wore off, she would start to feel hungry, and she would feel full after one bite. When she was not hungry, she would feel like vomiting when she saw food. The cycle goes back and forth.

"I used to be a 'foodie', but now I spend money to buy what I like to eat, but after seeing it, I feel very annoyed and can't even take a bite. I get very anxious and feel that I might as well not eat less," Xu Qing said.

Similar to Shen Ping's feelings, the effect of liraglutide on Xu Qing is not stable and sustained. At the beginning, Xu Qing used a dose of 0.6 mg each time. When she took the second injection, she felt that the drug was not as effective, so she increased the dose to 1.2 mg. Weight loss is also slowing. More than a month ago, Xu Qing's weight basically maintained a trend of losing 2 pounds a week. After a month and a half, she could only lose more than 1 pound a week, or basically the same.

Xu Qing wants to lose weight to 110 pounds through liraglutide, and then continue taking orlistat to maintain it. If the target weight is not reached by mid-October, she will stop the injections and think of other solutions. "If liraglutide fails, I may give semaglutide. Start with the less effective ones first to build up tolerance." .”

During the first two weeks of Zhao Yun's use of semaglutide, the dose was 0.25 mg each time, and was increased to 0.5 mg in the third week. At first, like Xu Qing, she had severe physiological reactions: she woke up every morning with panic and nausea. When I see food, especially greasy food, I feel nauseated and retching. When I feel hungry, I don't want to eat anymore after four or five mouthfuls. After digestion, I start to have diarrhea.

The vicious cycle is not just physical. Zhao Yun's work requires a high degree of concentration, but when her blood sugar rises, she becomes very tired, and it becomes very difficult to maintain energy. The pressure is great, and her sleep time is greatly compressed, making her even more tired. The physical discomfort after the injection made her work status even more "offline", and the deterioration of her work status virtually increased her psychological pressure. "I feel extremely broken. If I hadn't been sick, I wouldn't have suffered this because of weight loss," she said.

The number on the scale was going down, but Zhao Yun wasn't happy. "It's good to lose weight. I can wear clothes that I couldn't wear before. But losing weight is not my goal. I feel that my thinness is unhealthy and it is the result of physical discomfort. Restoring health is more important."

GLP-1 drugs have been used clinically for 10 years

GLP-1 is an incretin secreted by the human body itself. It can "intelligently lower blood sugar". That is, GLP-1 only exerts its blood sugar-lowering effect when blood sugar is high. When blood sugar is normal or low, it will not lower blood sugar. It exerts a hypoglycemic effect and avoids the occurrence of hypoglycemia. At the same time, it also increases the feeling of fullness and delays gastric emptying. However, GLP-1 can only exist for a few minutes before being degraded and cannot be used directly as a drug. So researchers structurally modified GLP-1 to form GLP-1RA.

The “star” semaglutide is not the first GLP-1 drug. Chen Haibing introduced that GLP-1 drugs have been used clinically for more than 10 years. According to her recollection, the GLP-1RA initially used was the imported drug Bymida (exenatide) developed by the multinational pharmaceutical company Eli Lilly (LLY.US), which was used to control postprandial blood sugar. She remembered very clearly that there was once a patient who was very sensitive to this drug. He took it for three months and lost 40 to 50 pounds. But it requires two injections a day, which is inconvenient.

Exenatide did not occupy a high market share, but after it, three generations of GLP-1 “drug kings” emerged, namely liraglutide, dulaglutide and semaglutide.

Semaglutide was initially approved by the FDA in December 2017 for blood sugar control in patients with type 2 diabetes. In the SUSTAIN series of studies, semaglutide defeated other anti-diabetic drugs such as exenatide and liraglutide, and showed superiority in reducing the weight of subjects. The STEP1 study provides more definite evidence of its weight loss effect. After using Wegovy for 68 weeks, trial participants lost an average of 14.9% of their weight.

Chen Haibing told The Paper that semaglutide became "popular" after it was approved for weight loss indications abroad. Before it entered the country, many people had already asked about it. Since then, its scope of use has expanded beyond the group of diabetic patients. Many people who want to lose weight have found the drug through various channels, and then shared it through social media, making it further "out of the circle".

Today, semaglutide faces many domestic and foreign competitors. Eli Lilly’s Tirzepatide (trade name: Mounjaro) attracts the most attention. In July this year, the results of a phase 3 clinical study showed that tilpotide could cause trial participants to lose an average of 21.1% of their weight after 12 weeks and an average of 26.6% of their weight within 84 weeks. "There are still many domestic GLP-1 drugs on the way, many of which are specifically targeted at weight loss indications." Chen Haibing said.

 

GLP-1RA has been approved for marketing. The content of the chart is compiled by ThePaper Technology based on public information.

According to Chen Haibing, currently, GLP-1 drugs are generally used clinically for obese patients with type 2 diabetes. "The price of semaglutide is relatively expensive, and most people with diabetes can just use metformin. For some people whose blood sugar is not particularly easy to lower, and who are combined with cardiovascular diseases, such as those who have had cerebral infarction, myocardial infarction, or are obese or fat. Patients with liver, proteinuria, renal impairment, etc. will benefit more from using this type of drug."

She also pointed out that this is an empirical choice, and the instructions for semaglutide do not limit it to obese people. “In our daily work, we usually use the drug in the mouth.” In addition, it is not All GLP-1 drugs have cardiovascular protective effects. Currently, only liraglutide, semaglutide, and dulaglutide have been shown to reduce cardiovascular events.

Although the weight loss effect is good, we still need to treat it rationally

Chen Haibing said that GLP-1 drugs have a good weight loss effect, but they cannot be abused. "Nowadays, everyone seems to want to use this type of drug. I think we should treat it rationally and not follow the trend."

In fact, GLP-1 drugs are not effective for everyone. On August 2, local time, an article titled "Four Key Questions About the New Wave of Anti-Obesity Drugs" published by Nature pointed out this point: "A small number of people are taking GLP-1 There is very little weight loss with the drug, and the reasons for this are not yet fully understood."

Chen Haibing said that some people are not sensitive to this type of drug, which may be related to the genetic polymorphism of the GLP-1 drug receptor. According to her, the Tenth Hospital has launched a genetic test related to the efficacy of GLP-1 drugs, priced at 360 yuan. “If the genetic test shows that the patient is not sensitive to GLP-1 drugs, there is no need to waste money.”

Under the brilliance of the “magic pill for weight loss”, the risk of side effects cannot be ignored. For example, semaglutide can cause adverse reactions, most commonly nausea and vomiting, which may occur in about 8% of patients

Discontinue medication. After stopping taking semaglutide, people have to face the fact that their weight will rebound. If they want to maintain their weight loss results, they may need long-term or even lifelong medication.

However, the safety of long-term use of GLP-1 drugs remains to be tested. In May this year, the EMA issued a thyroid cancer risk warning for both semaglutide and tilpotide. On October 5, a study published in the Journal of the American Medical Association (JAMA) showed that weight loss and hypoglycemic drugs such as Wegovy and Ozempic may increase the risk of gastric paralysis, pancreatitis, intestinal obstruction, and biliary tract disease in non-diabetic patients. risks of. In March this year, the EMA also issued a safety warning that three patients who used Ozempic and Saxenda to lose weight were prone to suicide and self-harm.

"This type of drug has the risk of promoting the occurrence of thyroid cancer, so a thyroid ultrasound is needed to check for the presence of thyroid nodules. Related blood tests are also needed because it may induce pancreatitis. Many people have gastrointestinal reactions after taking the drug , such as nausea, vomiting, etc., thought to be side effects of the drug, but in fact it may be pancreatitis." Chen Haibing said.

Out of stock is also a problem. Starting in the first half of 2022, the Australian Therapeutic Goods Administration (TGA), FDA, and EMA have successively issued shortage warnings for semaglutide. The shortage of Wegovy has prompted many American obese patients to turn their attention to diabetes drugs, causing Ozempic and Saxenda to also fall into shortages. In July this year, the FDA stated that tilpotide, which has not been approved for weight loss indications, also experienced intermittent shortages.

In Chen Haibing’s impression, the ten hospitals in the past were allocated at least 50 doses of semaglutide every month, which would be gone in two or three days, so the hospital was out of medicine most of the time. Starting from the second half of 2023, the situation will improve.

Chen Haibing believes that the enthusiastic pursuit of semaglutide has led to a shortage of medical resources to a certain extent. "The dose for weight loss is greater than the dose for type 2 diabetes. As the domestic indication for weight loss has not yet been approved, the needs of type 2 diabetes should take priority over the needs of beauty."

"March and April this year were the most painful period. The whole Shanghai was out of medicine, and many of them were bought by scalpers. Medicines that originally cost 400-500 yuan were sold for 900-1,000 yuan, and medicines that originally cost 850 yuan were sold for 1,500 yuan. ." Shen Ping experienced this round of "drug withdrawal" personally. In order to get semaglutide, he had to go far away and went to Fengxian and Lingang.

In fact, not every hospital can prescribe semaglutide for hyperinsulinemia. “Some hospital systems can only prescribe semaglutide for type 2 diabetes. Whenever I encounter a situation where hyperinsulinemia cannot be prescribed, I ask the doctor to diagnose type 2 diabetes. Shen Ping said that he has a small wish: "I hope more patients with hyperinsulinemia can use this drug."

Behind the craze for "miracle weight loss pills", a key question is, what is "obesity" or "overweight"? Currently, the body mass index (BMI) is commonly used internationally to measure the degree of fatness and thinness of a human body. Its calculation method is weight (kg) divided by the square of height (meters). According to the standards set by the World Health Organization (WHO): a BMI between 18.5 and 24.9 is within the normal range, greater than 25 is overweight, and greater than 30 is obese. China's BMI classification is slightly different: a BMI between 18.5 and 24 is normal, a BMI between 24 and 28 is overweight, and a BMI greater than 28 is obese.

Wegovy also states on the instructions that it is suitable for obese patients with a BMI ≥ 30 kg/㎡, or overweight patients with a BMI ≥ 27 kg/㎡ and at least one comorbidity.

In the aforementioned Nature article, Sarah Nutter, a psychologist and obesity stigma researcher at the University of Victoria in Canada, said: “There are concerns that the presence of these drugs will exacerbate eating disorders and weight shame. This is a place where body anxiety has no place. In a world that is no longer around, what we need to do is better understand the relationship between health and weight." Geoff Ball, a clinical researcher on childhood obesity at the University of Alberta in Canada, also said: "Health exists in people of all sizes. There is no right weight."