Every reporter: Lin Zichen Every editor: Liang Xiao
28-year-old Daming (not his real name) has always had a desire to lose weight. In June 2022, Daming heard from a friend about the "miracle drug" for weight loss - semaglutide.
On the other side of the ocean, the weight loss effect of semaglutide has long been known, and even Musk shared his experience of losing 9 kg a month with the help of Wegovy (semaglutide trade name) on Twitter.
You can "lie down and lose weight" and lose more than ten pounds a month... This hypoglycemic drug, which was originally used for type 2 diabetic patients, has become popular in China as a "diet drug". For Daming, who has not weighed less than 200 pounds since the age of 15, semaglutide is indeed very attractive.
In June 2021, semaglutide was approved for obesity in the United States
Image source: Screenshot of the FDA's official website
On June 25, 2024, the obesity indication of semaglutide was approved in China. However, before this, domestic users had already obtained this drug through various ways (previously, the "Daily Economic News" had published an article entitled ""One injection a week, 20 pounds per month"? CDE has not been released yet! GLP-1 hypoglycemic drugs have become the "underground darling" of dieters).
Unlike many people who are not actually "obese" but "abuse" semaglutide, Daming has a body mass index (BMI) above 30 and is obese. However, before he had time to celebrate his weight loss of more than 20 pounds, thyroid cancer came to his door. In the interview, when it comes to the "miracle drug" for weight loss and its possible side effects, Damin, who claims to be optimistic, becomes very sensitive, "Optimism is all fake" and "If there was a time machine, I would definitely not use semaglutide, nor would I use any diet pills".
Is my cancer related to a "miracle drug" for weight loss?
In August 2023, Daming accepted the annual physical examination arranged by the unit as usual. When undergoing the color ultrasound examination, the doctor said "huh". Subsequently, he was told that his thyroid gland had a "not very good" nodule and that it was more likely to be malignant.
At the time, Daming's mind was a little confused. No one in my family has ever had thyroid cancer, and I have no history of other cancers, and I was only 27 years old at the time, how could I get it? Moreover, in the thyroid examination before obtaining semaglutide, the volume of this nodule was only 0.2cm×0.2cm, which showed that it was benign, why did the nodule increase to 0.5cm×0.5cm after 4 months, and it became malignant?
On June 25, the weight loss indication of semaglutide was approved in China. It has been nearly 1 year since Daming had a thyroidectomy, but he still has a question in his heart: Is his diagnosis of thyroid tumor related to the use of semaglutide?
On the one hand, the degree of malignancy of papillary thyroid carcinoma diagnosed by Daming is relatively low, and it takes several years or even longer for a benign nodule to develop into papillary thyroid carcinoma, while from the two diagnosis sheets, it only takes 4 months for Daming's nodule to develop from benign to malignant.
On the other hand, the FDA (Food and Drug Administration), which was the earliest approver of obesity indications, has its website showing that Wegovy's prescribing information contains a black box warning to inform healthcare professionals and patients of the potential risk of thyroid C-cell (myeloid cell) tumors. The black box warning is still in place late last year after the European Medicines Agency (EMA) released its assessment results confirming that there is no causal link between GLP-1RA (glucagon-like peptide-1 receptor agonist) and thyroid cancer.
司美格鲁肽常见的副作用（side effects）和黑框警告（boxed warning）
Image source: Screenshot of the FDA's official website
The reporter learned that semaglutide had not been approved for weight loss indications in China before, and the relevant information obtained by doctors was very limited, and it could not be directly related to the risk of thyroid cancer.
In this regard, Wu Xueyan, director of the endocrinology department of Peking Union Medical College Hospital, said in an interview with the reporter of "Daily Economic News" that he has not observed cases similar to Daming in clinical practice, but on the basis of the lack of relevant clinical trials, it can neither be ruled out nor determined that Daming's thyroid cancer is related to the use of semaglutide. "It's as if he's drinking water and eating at the same time, and it can't be said to have anything to do with eating or drinking."
Wu Xueyan said that thyroid nodules are very common. 99% of thyroid nodules are benign, less than 1% of thyroid nodules are malignant, and more than 95% are papillary carcinomas, which is an indolent cancer, and the number and size of thyroid nodules vary regardless of whether the patient is taking semaglutide or not. Medullary thyroid carcinoma originates from thyroid C cells and may be affected by GLP-1 agents, which need to be treated with caution until further in-depth observation confirms.
The side effects are not clear, and off-label drugs still need to be vigilant
Judging from the timeline, Daming started using semaglutide 3 months before the physical examination of the unit. For the next month or so, he injected semaglutide 0.25ml per week at the dose prescribed by the doctor. Daming lost more than 20 pounds of weight, and the effect far exceeded the data of "6% weight loss in 12 weeks" and "17% to 18% weight loss in 68 weeks" in clinical trials.
In fact, there is also a break during the medication of Daming. The reason why he did not take the medication continuously like other users was because he found that "lying thin" was not so comfortable. Damien said that because of the loss of hunger, he often forgot to eat and weakened, and if he returned to three meals, he was prone to nausea and vomiting. In addition, intermittent migraines also affect my work status.
In fact, this is the most common adverse reaction (gastrointestinal side effects such as nausea, vomiting, diarrhea, abdominal pain, loss of appetite, dyspepsia, etc.) that are written into the GLP-1 drug label. In addition to these, according to the statistics of the reporter of "Daily Economic News", the side effects of semaglutide have been confirmed to involve gastrointestinal diseases such as gastric paralysis, intestinal paralysis, intestinal obstruction, malnutrition or fatigue syndrome, and unproven potential associated diseases include pancreatitis, cholelithiasis and cholecystitis, renal failure, complications of diabetic retinopathy, medullary thyroid cancer (MTC), etc.
In addition, a study published May 22 in the International Journal of Impotence Research, a sub-journal of Nature, also showed that non-diabetic men who took semaglutide were more likely to develop erectile dysfunction.
Wu Xueyan told the "Daily Economic News" reporter that the industry's understanding of drugs often lags behind clinical practice, and at present, everyone's understanding of semaglutide is insufficient, and some serious adverse reactions may take time to verify. For example, GlaxoSmithKline's diabetes drug "Vindia" was approved for marketing in 1999, and was withdrawn from the market after nearly 10 years because it would increase the likelihood of heart disease by 28%~39%.
Therefore, although the indications for semaglutide are constantly expanding, the prescription of semaglutide needs to be extremely cautious for people who lose weight other than the legally approved indications. Wu Xueyan said that he does not advocate off-label medication. Many patients swear that they "bear their own risk" when they first use it, but if the patient has serious side effects or even sudden death during the medication, and thinks that the disease is related to the medication. At this time, regardless of whether the disease is related to medication or not, because the doctor's prescription is off-label and does not fall under the category of "compassionate medication", the doctor and the hospital may get into legal disputes.
In addition, it is important for the doctor to fully inform the patient about the side effects and contraindications of the drug during the prescribing process. Daming remembers that the doctor prescribed semaglutide and Chinese medicine to help him lose weight. But in fact, according to the FDA's official website, semaglutide should not be used in combination with herbal products used for weight loss.
Image source: Screenshot of the FDA's official website
Can't escape the rebound of weight loss, some studies say that 2/3 of the weight regains after stopping the drug
At present, the number of obese people is increasing. A March 4 report by the World Obesity Federation predicts that the economic cost of global overweight or obesity could reach $4.32 trillion by 2035, equivalent to 3% of global gross domestic product, if governments fail to take effective containment or prevention measures.
In this context, it is not difficult to understand the explosion of semaglutide. In 2023, the sales of Novo Nordisk's star product will reach 145.811 billion Danish kroner (about 21.201 billion US dollars), a year-on-year increase of 88.78%, accounting for 62.78% of total revenue. Among them, Wegovy's revenue was 31.343 billion Danish kroner, or about 4.557 billion US dollars, a year-on-year increase of 407%.
However, studies have shown that users are prone to weight regain after discontinuation of semaglutide. In April 2022, a study published in the journal Diabetes, Obesity and Metabolism showed that after stopping the use of semaglutide drugs such as Wegovy and Ozempic, two-thirds of the weight lost after one year of use would grow back.
On February 19, 2024, researchers from the University of Copenhagen published a paper in the journal eClinicalMedicine, a journal affiliated with The Lancet, also showed that within one year after the discontinuation of GLP-1 weight loss drugs, the previous weight loss usually regained more than two-thirds, but people who exercised during treatment with GLP-1 weight loss drugs did not have the same weight regain tendency after stopping the drug.
These studies suggest that while semaglutide has a significant effect on weight loss, weight management needs to be considered in addition to pharmacotherapy.
At present, Daming's weight has rebounded back to 200 pounds. After half a year of recuperation after surgery, he decided to return to the weight loss strategy of "eating less and moving more", and admitted that the main reason for his previous weight loss failures was that he did not recognize the health hazards of obesity and was not self-disciplined enough, which may be the reason why many people choose to lose weight through semaglutide.
"My life hasn't changed much now, and sometimes I forget that I've had cancer. But if my family wants to use semaglutide, I will definitely not approve of it. Daming told reporters that if there was a time machine, he would definitely not use semaglutide, nor would he use any diet pills.
Not being able to gain muscle and not being happy, losing weight too quickly beware of these consequences
In March, Wegovy was approved by the FDA for a new indication to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and obesity or overweight. At the same time, more indications such as non-alcoholic steatohepatitis (NASH), neurological diseases (such as Alzheimer's disease, Parkinson's), and polycystic ovary syndrome (PCOS) are still under observation in clinical trials.
Wu Xueyan was not surprised by this. He told reporters that many diseases of modern people are related to obesity, and most of these indications are related to obesity. For example, in patients with non-alcoholic fatty liver disease, the liver is enlarged by fat like foie gras, obesity is formed by the accumulation of fat in the subcutaneous and internal organs, and the fat of obese people is accumulated in all organs of the body, of course, including the liver, the central factory of fat processing.
Wu Xueyan believes that in addition to reducing the number of surgical procedures such as "gastric incision", the application of semaglutide in weight loss may affect many industries, such as triggering changes in people's diet and exercise habits, and the sales of home ventilators (obese people are more likely to have sleep apnea) may also decline.
So, can semaglutide completely eliminate people's obesity anxiety?
"Good grades are the result we want to pursue, but helping children with homework and helping children do their homework is definitely different." Wu Xueyan made a vivid analogy, using diet pills to lose weight is like writing homework for children, but exercise to lose weight is like tutoring children to do homework, in the process of exercise, fat is converted into muscle, weight may not drop quickly, but it can speed up blood circulation, enhance cardiopulmonary function, stimulate the body's internal production of growth hormone and endorphins, so as to delight the mood and enhance the immune system.
On the contrary, weight loss pills not only do not "gain muscle", but also cause the user to lose muscle volume, sagging skin, and even cause dull skin.
"Many people are losing weight now, but in fact, Chinese often say 'take care' when they are separated." Wu Xueyan reminded that losing weight too quickly is not good for the body, and body fat is like Dongting Lake, which plays the role of "buffering the water level of the Yangtze River". For example, lipopolysaccharide is a toxin produced by bacteria that have died of gram-negative bacteria, which can enter the human bloodstream through the intestines, and normally the fat captures and dilutes it. But if a person loses weight too quickly (losing more than four or five pounds a month), then the harmful substances stored in the fat will be released, beyond the upper limit of the body's processing, and it will cause unexpected damage to the heart, liver, kidneys and even other organs.
"A big reason for obese people (obesity) is that they eat too much, eat too well, and have too much energy. Rather than promoting diet pills, the public should be reminded to relax while keeping their mouths shut and moving their legs. Wu Xueyan said.
National Business Daily