Source: Pixabay
Written by Zhou Yebin
"One injection a week, easy to lose ten pounds". Since last year, a diet loss needle has begun to become popular around the world, and it has not only been sought after by Chinese social media netizens, but also celebrities such as Elon Musk have publicly come forward to endorse it. Musk claimed on social media that he lost a full 30 pounds (about 13.6 kilograms) through Wegovy (generic name simeglutide injection) and intermittent fasting.
This kind of Internet celebrity weight loss injection, which is actually a hypoglycemic injection, is currently approved in China for only type 2 diabetes, but according to many domestic media reports, due to the crazy robbery of weight loss groups, diabetic patients often lack medicine.
Past life of slimming needles
This slimming needle is an analogue of the natural hormone secreted by the body, glucagon-like peptide-1 (GLP-1). GLP-1 was first noted to stimulate the pancreas to secrete insulin while inhibiting glucagon production that is opposite to insulin. This effect is the "heavenly choice" drug for type 2 diabetes.
GLP-1 drugs can be as popular as they are now, and it is by no means the result of honestly sticking to the acre of type 2 diabetes - what everyone is talking about now is weight loss injections, not hypoglycemic injections.
So how did GLP-1 become a weight loss weapon again? Type 2 diabetes is a metabolic disease (type 1 diabetes is an autoimmune disease) and is often associated with obesity, lack of exercise and other factors. Therefore, the subjects recruited in the clinical trials of type 2 diabetes drugs are often obese patients, which makes hypoglycemic drugs a "smooth" thing in observing "weight loss".
However, hypoglycemic drugs do not necessarily lose weight, in fact, many diabetes drugs will gain weight.
However, GLP-1 drugs are very different from previous hypoglycemic drugs. In the clinical trial of type 2 diabetes, a number of GLP-1 drugs lived up to expectations, and the drug group showed different degrees of weight loss compared with the control group.
For example, in a clinical trial of type 2 diabetes in which the average baseline weight of a subject was about 99.3 kg, a dose of 1 mg per week was used, and an average weight loss of 5.7 kg after 40 weeks.
In addition to semeglutide, a variety of GLP-1 drugs have shown weight loss in clinical trials of type 2 diabetes, which has led some doctors to use some GLP-1 off-label (i.e., beyond approved drug indications) to help people lose weight or control weight.
Switching to weight loss was a blockbuster
It is difficult to lose weight, which almost no one has objections, but it is even more difficult to make an effective weight loss drug.
Orlistat, a more widely used weight loss drug, as a lipase inhibitor, can inhibit the absorption of fat, and in multiple clinical trials, after one year of use, subjects lost 2-3 kilograms compared with the control group. It should be known that the BMI of weight loss pills is often more than 30, the weight of 100 kg is average, and 2-3 kg is really a difference that can only be seen with a magnifying glass.
There is a "clinically significant weight loss" criterion in medicine, which refers to a weight loss of 5%. 5% may not seem like much, but many diet pills still cannot cross the mountain in most obese patients under the addition of exercise and diet control.
The safety profile itself is very good, and many subjects have achieved significant weight loss in clinical trials of type 2 diabetes. Therefore, some GLP-1 drugs that lose more weight began to be sent to the battlefield of weight loss - directly recruiting obese patients without type 2 diabetes to do clinical trials, to see if diabetes is good, whether it is a diet drug.
The first to start was liraglutide, and the results were a blockbuster. In a 2009 clinical trial published in The Lancet, in subjects with BMI30-40, injecting 1.2, 1.8, 2.4 and 3.0 mg of liraglutide per day in the context of exercise and dietary control, with an average weight loss of 4.8, 5.5, 6.3 and 7.2 kg at 20 weeks, compared with placebo losing only 2.8 kg, compared with the aforementioned orlistat 4.1 kg.
And to achieve clinically meaningful weight loss, that is, the proportion of subjects who lost 5% of weight, the placebo group was 30%, orlistat 44%, and what was 3mg liraglutide? 76%！
These are 20 weeks of data, and later studies showed the weight loss ability of liraglutide over a longer time frame, such as a clinical trial of more than 3000 people (baseline average weight of about 106 kg) showed that 62.3% of 3mg liraglutide users who followed 56 weeks (more than one year) lost more than 5% of their weight loss, and lost more than 10% of their weight up to 33.9%, with an average weight loss of 9.2%.
With amazing weight loss effects, in 2014, the FDA approved liraglutide to help obese patients lose or control weight, which is also the first weight loss injection. (Note: Liraglutide was approved for diabetes in China in 2011, only one year later than the FDA, but there is no indication for obesity in China; The original drug began to enter medical insurance in 2017, the patent has expired, and the first biosimilar of liraglutide in China was approved on March 30. ）
Don't watch liraglutide rub the predecessors of diet pills such as orlistat on the floor, but compared to the new generation of GLP-1 drugs, it is not a thing. In the phase III clinical trial to study the effect of weight loss, the average weight loss range was 14.9% in 68 weeks, with more than 80% of subjects losing more than 5% and 30.9% of subjects losing more than 20%.
This is not over, liraglutide and semeglutide are both developed by Novo Nordisk, and there is also a pharmaceutical company in the GLP-1 field that also has a prominent position - Eli Lilly. In July 2022, Eli Lilly announced the results of its phase III clinical trial of its new generation GLP-1 drug tirsepatide (tirzepatide) for the treatment of obesity: three doses, 5mg, 10mg and 15mg, 72 weeks of follow-up time, baseline weight of about 105 kg, average weight loss distribution of 15%, 19.5% and 20.9%.
Weight loss results obtained by bariatric surgery, including gastric bypass surgery, are also an average weight loss of 25-30% within 1-2 years. More than one-third of participants in the high-dose tisipatide group lost more than 25% of their weight, comparable to bariatric surgery.
Tesiparatide and semeglutide are not the same as their predecessors, they are double agonists, not only an analogue of GLP-1, but also similar to another hormone, GIP. The drug is currently only approved by the FDA for diabetes, but the industry believes it will soon be approved for the treatment of obesity.
What are the risks of diet shots?
The overall safety profile of GLP-1 drugs is very good, which is why they have been developed as weight loss shots. However, this does not mean that drugs such as semeglutide are risk-free for anyone to use, or that there are no adverse reactions worthy of vigilance.
All GLP-1 drugs mention a scary-looking risk: thyroid C cell growth or cancer. Many people may also be dissuaded by the risk of this type of cancer, but this is a phenomenon observed in rat models, and there is no evidence that GLP-1 drugs increase thyroid C-cell carcinogenesis after clinical trials or marketing. As a precaution, GLP-1 is not currently recommended for people with a family history of a few endocrine-related cancers, such as medullary thyroid cancer. But for most people, the scariest cancer sounds like it's not a danger to worry about when using diet shots.
In addition, acute pancreatitis has occurred in users during the use of GLP-1 drugs. However, it is doubtful whether these drugs actually increase the risk of acute pancreatitis. However, acute pancreatitis is very dangerous, so pay attention to whether there are relevant signs when using slimming injections.
There is also a common adverse reaction of weight loss injections, the mechanism of GLP-1 weight loss is not to increase the body's energy consumption, but to reduce energy intake by increasing satiety and delaying the emptying of food in the digestive tract. It is precisely because of this mechanism that common adverse reactions include nausea, vomiting, constipation or diarrhea, which are closely related to eating and digestive tract activity. In phase III clinical trials such as semeglutide for the treatment of obesity, nausea, vomiting, constipation and diarrhea occurred in 44.2%, 24.8%, 23.4% and 31.5% of subjects, respectively.
Another common side effect that easily causes panic but has little effect once the user notices it is an increase in resting heart rate. This is due to the fact that GLP-1 receptors are also present in the heart, and the resting heart rate increases by an average of 1-4 beats per minute with GLP-1 drugs. This can raise concerns about whether the risk of heart disease increases in the long term. However, in clinical trials of diabetes and obesity, GLP-1 drugs have shown cardiovascular disease benefits, not increased risks. Therefore, at least in the applicable population, no harm has been shown.
In fact, the overall safety of GLP-1 drugs is very good, the use of weight loss injections, individuals should pay attention not to extremely rare serious adverse reactions, but how to face the gastrointestinal side effects of such drugs due to the mechanism of action.
Who is exploring their bodies?
Many people may wish to get a shot when they read this, not asking for a 20% reduction, and a 5% reduction is also good. This kind of weight loss also triggers a topic that we must pay attention to in the face of weight loss injections - how to rationally view the role of such drugs and avoid abuse.
It can be said to be a revolutionary breakthrough for obesity treatment. When it comes to weight loss, we all think of controlling diet and increasing exercise, commonly known as "control your mouth and open your legs". But in reality, not only are these two extremely difficult to achieve, but the actual weight loss effect that most obese patients can obtain may also be average.
Refer to the control group in the phase III clinical trial of semeglutide and tisiparatide obesity. The two phase III clinical trials were conducted on the basis of diet control and increased exercise, which means that both the control and medication groups reduced caloric intake and increased physical activity.
Moreover, the dietary control and increased exercise in these clinical trials are regularly individualized auxiliary support provided by professional nutritionists or health counselors, and are designed to be 150 minutes of physical activity per week, combined with a daily calorie intake of 500 calories less than estimated at the time of the trial. In real life, most people will not have such good counseling support, and second, diet control and increased exercise may not be able to achieve the above level.
But this revolutionary weight loss effect also brings some irrational expectations. To analyze the weight loss effects of any GLP-1 drug, we must pay attention to whether the people targeted by such drugs are really obese or generally overweight.
Whether it is semeglutide with a weight loss of 15% or ticipatide with a weight loss of 20%, their phase III clinical trials are based on BMIs above 30 or 27, as well as underlying diseases related to overweight. The actual recruited subjects, the average weight is about 105 kg, the average waist circumference is about 114 cm, the average BMI is about 38, more than 94% of the subjects have a BMI of more than 30, and even nearly one-third of the subjects have a BMI of more than 40. It can be said that these subjects do face the health threat of obesity and there is a need to lose weight, that is, there is a medical need for weight loss.
In people who are not so heavy, weight loss injections may not be able to replicate the results of phase III clinical trials, and one injection will lose 15% of body weight.
China has not yet approved any GLP-1 drugs for weight loss, and it is not uncommon to discuss weight loss injections and purchase weight loss injections online.
And in real life, the audience of Internet celebrity weight loss injections is a big fat person who is forty or fifty years old and sick? Or young people who are overly anxious about body shape due to social prejudices? In the reports of Internet celebrity slimming injections, you can often see the description of planting a large number of grass on social platforms such as Xiaohongshu and B station. Based on the main user population attributes of these platforms alone, there is not much intersection with the clinical trial population of drugs such as semeglutide. How significant is it for young people who are relatively healthy and are not considered obese or severely obese? There are many reasons for us to be suspicious.
How many of the semeglutide slimming injections that have become Internet celebrities are given to people with real medical weight loss needs?
From the perspective of weight loss, the reference to the most weight-losing tisiparatide in lighter diabetic patients achieved much smaller weight loss than obesity patients, those who just want to make themselves better looking ordinary people may not be able to get the desired results.
Moreover, the weight loss effect of drugs such as semeglutide increases with the dose. China has not approved these high-dose GLP-1 drugs for weight loss. The highest dose approved for semeglutide in China is only 1mg, which is much lower than the 2.4mg of Wegovy approved for weight loss abroad. Relying on the low-dose version of diabetic patients to lose weight will have a limited effect: 1 mg of semeglutide can lose less than 6% of weight at 40 weeks in diabetic patients with an average weight of 99.3 kg. Take the hypoglycemic injection of diabetic patients as an Internet celebrity weight loss injection, I am afraid that the effect will not be as good as the hype on the Internet.
Slimming injections such as semeglutide can bring long-term weight loss gains, but there is a premise here, that is, to use it all the time. Like in clinical trials, after using the 2.4mg slimming version of semeglutide for one year, the drug was stopped for one year, and the weight lost by the previous injection returned two-thirds. People who are not obese, people who do not really affect their health because of obesity, are they really willing to get injections for a long time - weight loss injections are not cheap, or are they just a few injections in the end, and they are short in life for a few days or months?
More importantly, people who do not have obesity in medicine, even if they lose a few pounds of weight through weight loss needles, can they have health benefits? For these already healthy people, has the digestive discomfort caused by weight loss injections become an unnecessary "sin"? Even the increase in basal heart rate requires greater vigilance?
Just as we cannot ignore the health threats posed by obesity, we cannot ignore the body anxiety that is so common in today's society. Movies, fashion magazines, advertisements, and even social media often convey us body images that are not necessarily healthy or even unrealistic. In recent years, eating disorders such as anorexia have also increased rapidly in China, and the mechanism of action of GLP-1 drugs happens to reduce appetite and delay the emptying of the digestive tract. When diet shots enter the field of vision of young people affected by body anxiety along with various herbs, will they bring a serious risk of completely deviating from the original intention of these drugs?
Whether used to lower glucose or lose weight, GLP-1 drugs are prescription drugs that need to be judged and guided by a medical professional. With all kinds of hype on the Internet, what we see is that diabetics are beginning to have difficulty obtaining drugs that are essential for them (them), and at the same time, many people who do not need drugs such as semeglutide to lose weight spend a lot of money on their bodies without any medical guidance.
In the face of the growing problem of obesity, we need to make GLP-1 drugs such as semeglutide a weight loss needle to help some truly obese patients. But we can't get lost in the anxiety of body shape caused by social prejudice, and let body image, which has nothing to do with health, kidnap the weight loss needles that should be used to treat obesity.
Bibliography:
1.https://www.ncbi.nlm.nih.gov/books/NBK551568/
2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520185/
3.https://www.novomedlink.com/diabetes/products/treatments/ozempic/efficacy-safety/ozempic-and-weight.html
4.https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.119.041022
5.https://pubmed.ncbi.nlm.nih.gov/19853906/
6.https://www.novomedlink.com/obesity/products/treatments/wegovy/efficacy-safety/clinical-trial-1-results.html
7.https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
8.http://www.xinhuanet.com/politics/2020-12/23/c_1126896810.htm
9.https://www.ncbi.nlm.nih.gov/books/NBK551568/
10.https://pubmed.ncbi.nlm.nih.gov/32103407/
11.https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
12.https://www.sixthtone.com/news/1007576
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