MOSCOW, December 28, Tatyana Pichugina. Science reports a real medical breakthrough: GLP-1 agonists, approved for the treatment of type 2 diabetes, were found to lead to noticeable weight loss. Elon Musk admitted that he lost weight this way. Research has revealed a number of other beneficial properties of these drugs. understands how strong the evidence is and what the side effects of this therapy are.
The Mystery of Insulin
In the 1980s, a young endocrinologist from Canada, Daniel Drucker, came to Harvard to study incretin hormones, produced in the intestinal mucosa and brain. He soon discovered that glucagon-like peptide-1 (GLP-1) stimulates insulin production.
This hormone, together with glucose-dependent insulin-like peptide (GIP), is released after eating. They encourage cells to break down glucose from food. Decomposition products are deposited in muscles and fatty tissues. At the same time, glucose synthesis in cells is also suppressed. As a result, blood sugar levels decrease.
Insulin is produced in the beta cells of the pancreas. If this does not happen, type 1 diabetes occurs, which requires hormone injections.
Type 2 diabetes is when cells lose sensitivity to insulin. This requires hypoglycemic drugs.
Drucker's discovery paved the way for the development of new drugs for type 2 diabetes. Several patents were issued, but the prospects for commercialization seemed illusory.
“The pharmaceutical industry was underdeveloped. Few people were involved in technology transfer at universities,” Drucker recalled.
It was almost 20 years later that the first drug that mimicked GLP-1, exenatide, was approved. The basis was a peptide from the venom of the Arizona serpentine tooth. Then liraglutide came along. There are now several GLP-1 agonists on the market, bringing scientific fame to their developers and huge profits to their manufacturers.
Side effect
In the 1990s it was found that injections of GLP-1 into the brain mice reduce appetite. Tests were carried out on 20 healthy men. Those who received the drug intravenously ate a more modest lunch after a large breakfast than those who received the placebo. It looked encouraging.
In 2014, the United States approved liraglutide from the Danish company Novo Nordisk, intended for diabetics, for the treatment of obesity. However, it has not gained popularity because it must be administered twice a day. In 2016, a long-acting drug, semaglutide (Ozempic), was introduced to the market. One injection per week is enough. This medicine, under the commercial name Vegovi, was approved for use in obese patients in 2021. And recently it was added tirzepatide, an analogue of two hormones at once — GLP-1 and GIP, developed, like exenatide, by the American company Eli Lilly.
An experiment was conducted in 2021. Almost two thousand volunteers with a body mass index of 30 or more who did not have diabetes were injected with semaglutide once a week. All followed a low-calorie diet and were physically active. After 68 weeks, they lost an average of 15 kilograms. Side effects include nausea and diarrhea.
As you know, those who have lost weight usually regain their weight quickly. According to the Maccabi Health Service in Israel, the effect lasts for three years. These findings are based on observations of 23 thousand diabetics who took the drug for at least two years. The study was supported by the pharmaceutical manufacturer.
On the other hand, scientists from Canada have found that GLP-1 agonists increase the risk of gastrointestinal diseases. Pancreatitis — by nine percent, intestinal obstruction — by 4.22, gastroparesis — by 3.6. It's not much, but it's something to keep in mind.
«It is vital that people take these drugs only as prescribed by a doctor and are treated under the supervision of specialists,» emphasizes physiologist Simon Cork from Anglia Ruskin University in an interview with Science Media Center.
Nevertheless, an unhealthy excitement arose in society, which was facilitated by Elon Musk and tiktokers. According to Science, 1.7% of the population in the United States takes this type of drug. A shortage has formed, and counterfeits have already appeared.
Meanwhile, the risks have not been properly studied, there is no data on patients with a body mass index of 27 and below, which is not yet classified as obesity.
In Australia, where semaglutide was approved in September 2022, there are numerous cases of overdose, which often result in hospitalization. In November, a 56-year-old woman who was prescribed the drug for obesity died. Doctors deny that this was the cause of death, relatives are sure of the opposite.
And then it suddenly turned out that these drugs have a positive effect on other body systems.
In November, the New England Journal of Medicine, a major medical journal, published the results of a clinical trial (funded by Novo Nordisk) showing a significant reduction in the risk of death from cardiovascular disease. 17 thousand people with obesity and heart problems, but without diabetes, took part. Therapy lasted an average of 34 months.
Another study from the US showed that GLP-1 agonists reduce the likelihood of colorectal cancer. The discoverer of the drug, Dan Drucker, is actively researching its anti-inflammatory effects.
«GLP-1 agonists also reduce the complications of chronic metabolic disorders. We know this from clinical studies, but we do not understand the mechanism,» the scientist admits.
«There are still more questions than answers,» concludes Holden Thorpe, editor-in-chief Science magazine. But he adds: it looks like this is a “real breakthrough.”
Strictly as prescribed
«Semaglutide is a truly unique drug. We have been using it for more than five years, so it is unlikely that this is the discovery of the year. It has been sufficiently studied,» says the doctor in a conversation with — Guta Clinic endocrinologist, candidate of medical sciences Tatyana Gudozhnikova.
According to her, the drug is highly specific to the level of glucose in the blood — when the norm is reached, the sugar no longer drops. Therefore, it was approved for patients with obesity, but without diabetes.
The medicine is used by injection once a week. It reduces the feeling of hunger, increases the absorption time of food in the stomach and intestines, and reduces insulin resistance. And the mass of adipose tissue decreases.
Abroad, Gudozhnikova continues, the drug is included in long-term research programs such as SUSTAIN, PIONEER, STEP, where it is tested on volunteers with placebo groups for control.
«The Russian company Geropharm announced the creation analogue of semaglutide. It will go on sale after all the necessary studies are completed,» the expert notes.
The drug is suitable for many patients, but self-medication is dangerous.
“Sometimes it is recommended by fitness trainers and online consultants. This is fraught with serious consequences for the endocrine system and the entire body,” warns Gudozhnikova.
Only an endocrinologist can determine whether this drug is needed. Before prescribing therapy, the doctor will evaluate the condition of the thyroid gland, insulin resistance, and look for plaques in the vessels. That is, he will conduct a full examination.
The main contraindications include: ketoacidosis, pregnancy, a history of medullary thyroid cancer, renal failure (GFR less than 15), chronic heart failure of the fourth degree.
Weight loss therapy lasts from six months to a year under the supervision of a physician. . You need to undergo tests periodically.
Possible side effects are nausea, bloating, loose stools, headache, dizziness. If they occur, a doctor’s consultation and treatment adjustment are necessary.
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