In the endocrine department of the Second People’s Hospital of Guangdong Province, nurses are injecting drugs into type 2 diabetes patients to control blood sugar. Photo/Yali
Reporter Zhang Hua from Yangcheng Evening News
The trend of Musk’s weight-loss drug has blown into China. In recent years, GLP-1 drugs for lowering blood sugar and losing weight have surged in the global market, with the sales of semaglutide skyrocketing from $10.9 billion in 2022 to $21.2 billion in 2023. Many have been eagerly anticipating the approval of semaglutide injectable solution for long-term weight management, which has recently been approved for marketing in China. Over the past 20 years, there have been very few drugs approved for the treatment of obesity in China. Some endocrinology experts believe that this drug may completely change the landscape of obesity treatment.
Currently, in the weight-loss drug arena globally, leading giants like Novo Nordisk and Eli Lilly are in the forefront, with companies like AstraZeneca quickly following suit and developing over a hundred different drugs. So, can losing weight by injections and pills really make you effortlessly slim down?
Trend
New weight-loss drugs are popular worldwide, intensifying competition among pharmaceutical companies
Weight-loss drugs have always been a major focus of research for pharmaceutical giants, especially now as the trend is at its peak.
In fact, weight-loss drug research has not seen much success in the past. Drugs like sibutramine, phenylpropanolamine (causing cerebral hemorrhage), amineptine (causing pulmonary arterial hypertension), and fenfluramine (causing arrhythmia/death) that were approved for treating obesity were globally withdrawn due to severe adverse reactions.
It wasn’t until recent years that the development of safe and effective weight-loss drugs started to see the light. In June 2021, semaglutide, a drug developed by Novo Nordisk, was approved by the FDA for treating common obesity (brand name Wegovy “Nohe Ying”). It was the first new drug approved for controlling common obesity or overweight since 2014. In September 2021, it also received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Currently, Wegovy has been launched in over 10 countries and regions globally.
In April 2021, semaglutide was first approved in China for diabetes patients to control blood sugar, named “Nohetai”. However, amidst its global popularity, many in China have been skirting the rules by using this drug for weight loss.
On June 25, 2021, “Wegovy” was finally approved in China, specifically for use as an adjunct to low-calorie diet and increased exercise for the treatment of obesity (BMI ≥ 30kg/m²) or overweight (BMI ≥ 27kg/m²) in adult patients with at least one weight-related comorbidity, such as abnormal blood sugar, hypertension, abnormal blood lipids, obstructive sleep apnea or cardiovascular disease. Professor Chen Wei from the Clinical Nutrition Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, stated: “Given the very limited number of drugs approved for the treatment of obesity in China over the past 20 years, new medical weight-loss drugs can provide another treatment choice for patients, which has a profound impact on the clinical practice of obesity and related diseases.”
The pricing of Wegovy has not been disclosed yet, while “Nohetai” entered the national medical insurance catalog in the year of its launch in China and also underwent a price reduction earlier this year. The prices in public hospitals for the 1.5ml and 3ml formulations are currently 421.34 yuan/support and 716.28 yuan/support, respectively. However, semaglutide used for weight loss as “Wegovy” is not covered by medical insurance.
Globally, the sale of weight-loss drugs is booming, sparking enthusiasm.
In November 2023, Tirzpatid under Lilly was approved by the FDA for weight loss and officially went on sale in pharmacies in December. In the field of GLP-1 drugs, as Lilly and Novo Nordisk battle it out, no one is willing to miss out on this potentially boundless market, leading more and more pharmaceutical companies to join in. Roche spent $2.7 billion to acquire the diabetes and obesity therapy star company Carmot Therapeutics, AstraZeneca introduced Chieis Bio’s small molecule GLP-1 receptor agonist, Boehringer Ingelheim focused on advancing GLP-1R/GCGR dual-target agonist BI456906, and Merck also positioned its dual-target agonist at GLP-1R/GCGR…
Domestically, the competition in the market is also heating up. Survey data shows that there are over 100 drugs in clinical development stage targeting GLP-1, a weight-loss target in China.
Research
Product efficacy rivals surgical operations, with an average weight loss of 16.8kg in 16 months
Why is losing weight so difficult? The uncertainty lies in efficacy. “In reality, even if you cannot reach normal body weight, effective weight loss, achieving more than 5%, or even over 3% weight loss, can be beneficial,” says Chen Hong, Chief of the Endocrine Department at Zhujiang Hospital of Southern Medical University. This benefit can be seen in various aspects: Firstly, the reduction of chronic diseases, such as a significant decrease in cardiovascular diseases and even tumors; Secondly, life expectancy may increase.
Studies show that the average weight loss achieved by controlling diet and moderate exercise is 7%. Chen Hong points out that it is difficult for many obese individuals to lose weight, such as those with obesity genes, a BMI exceeding 40, making it difficult to achieve weight loss through conventional methods, where dietary control is just a drop in the bucket. “Weight loss is a battle of will, and the issue of controlling rebound is also crucial.”
Currently marketed GLP-1 mechanism weight-loss drugs have the allure of achieving weight loss rates almost comparable to weight-loss surgeries. Taking the global large-scale STEP series studies of Wegovy as an example, which included around 25,000 overweight and obese participants, the results showed that the weight reduction of the Wegovy treatment group on average reached 17% (16.8kg), which was sustainable for 16 months. Additionally, it can reduce waist circumference, lower visceral fat, improve blood lipids, delay the progression of prediabetes, etc.
For populations with a large body weight base, drug-induced weight loss is a relatively effective method. What is the principle behind this? Li Ping, Chief of the Endocrinology Department at the Second People’s Hospital of Guangdong Province, tells the reporter that the active ingredient in Wegovy, semaglutide, is a glucagon-like peptide-1 (GLP-1) analog. In terms of the mechanism of action, GLP-1 receptor agonists act by binding to and activating the GLP-1 receptor. GLP-1 receptors are present in several brain regions associated with appetite regulation. In obesity patients, they can help reduce hunger, increase satiety, and reduce food cravings, thereby helping patients reduce caloric intake and lose weight.
“Patients just need to inject once a week, similar to insulin injections for diabetes patients, injecting into the abdomen to control appetite and reduce weight,” Li Ping says. “Currently, Wegovy has not yet entered hospitals, but previously, the weight-loss effects of Nohetai, used for type 2 diabetes, were significant. We have patients who have been using it for six months with stable blood sugar levels, and weight loss of 20-30 kilograms.”
Cost
Significant muscle loss, and once stopping the drug, there might be further weight gain
So, will relying solely on medication be easy to maintain weight in the future? Not necessarily.
Although the weight-loss effects of drugs like semaglutide and other GLP-1 weight-loss drugs are powerful, continuous use is necessary, and there may be a “rebound risk” if the drug is stopped. Li Ping points out that once a drug reaches a certain efficacy, the subsequent weight loss magnitude will become smaller, potentially entering a bottleneck phase. Once the drug is stopped, reverting to previous unhealthy eating habits may lead to even more severe weight gain.
“You cannot rely on weight-loss drugs forever to maintain weight,” says Li Ping.
At the same time, some side effects associated with weight-loss drugs, such as nausea, vomiting, and diarrhea, have also garnered the attention of experts. Li Ping states, “About 10%-20% of patients using GLP-1 weight-loss drugs in our practices cannot tolerate them. Even starting from the smallest dose of 0.25 mg, some patients feel uncomfortable. Also, since injections are required once a week, some patients are afraid of needles.” According to medication compliance studies, fewer than half of diabetes patients using injectable GLP-1 can persist in using it for over a year, and only around 30% can continue usage for over two years.
Of course, for some obese individuals, perhaps injections and these side effects are not considered major issues. More importantly, out of the weight lost, approximately 40% may come from muscle loss, meaning that while losing fat, muscle mass can also decrease. Li Ping explains that ultimately, GLP-1 weight-loss drugs do not primarily reduce weight by metabolizing fat but by controlling a person’s appetite, reducing food intake and gastrointestinal motility to achieve “energy control.”
For middle-aged and elderly individuals, especially those needing to combat aging, reducing muscle mass bears a significant cost. “In fact, this is a clear side effect of simple diet control for weight reduction, such as meal replacements, dieting, etc., which easily lead to losing muscle mass during weight loss. This is why many people, after losing weight, feel loose skin because they lost muscle mass,” says Li Ping.
Professor Mu Yiming from the First Medical Center of the General Hospital of the PLA also pointed out: “Weight management should not merely aim at weight loss. It should also focus on sustaining weight loss after weight reduction and should involve the prevention and improvement of obesity-related risks and complications, metabolic benefits, and long-term health benefits.”
Since muscle loss can increase the risk of cardiovascular diseases and osteoporosis, undoubtedly, a new demand is emerging – lipid reduction combined with muscle gain is becoming the new direction for the development of a new generation of weight-loss drugs or “partners.” For example, Regenco reiterated its plans to enter the weight-loss race in 2024. Through combining trevogruMb and garetosmab in semaglutide, they hope to enhance the quality of weight loss for patients, achieving the effect of weight loss without losing muscle.
