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- At the fat level: scientists have found available "controllers" of appetite and blood sugar
At the fat level: scientists have found available "controllers" of appetite and blood sugar
Russian scientists have developed a new group of substances to combat diabetes and obesity. The new compounds work through a receptor that regulates sugar levels and appetite. Unlike well-known foreign drugs of this class, each of the registered molecules has a simpler and more technologically advanced structure, which simplifies its production. It will be possible to make a drug in the form of tablets from new substances, which will be especially important for those who are not comfortable with permanent injections. Read more about how the substances work and whether they can replace the scandalous Ozempic in the Izvestia article.
Appetite and blood sugar control
Scientists at Sirius University of Science and Technology have patented a group of substances aimed at combating type 2 diabetes and obesity. They work with the glucagon-like peptide-1 (GLP—1) receptor, a molecule that helps the body lower blood sugar levels and reduce appetite. When we eat, this receptor turns on itself, but people with diabetes and obesity lack its activity, the university told Izvestia. Therefore, scientists synthesize special drugs — artificial "assistants" that mimic the action of a natural hormone.
Sirius experts drew attention to one of the foreign analogues, the drug danuglipron. It is convenient because it can be taken orally in tablet form instead of injections. However, in clinical trials, patients often experienced nausea, diarrhea, and other stomach and intestinal disorders. Because of this, the developers withdrew the drug from clinical trials. The staff of the Translational Medicine Research Center has proposed a number of new low molecular weight GLP-1 receptor agonists with a structure similar to danuglipron, but representing a completely new type of potential drugs.
In addition, scientists have paid special attention to the convenience and practicality of producing new compounds. They have developed a simplified synthesis scheme that allows for the simultaneous production of several similar molecules, and also includes the stages at which substances that form crystals well are formed. Such intermediates are easier to clean and control their quality — this is especially important during the transition from laboratory synthesis to industrial production. The research was carried out as part of a major project to create drugs against type 2 diabetes and obesity.
At the first stage, the scientists tested their development on cell cultures. The researchers tested how the compounds activate the GLP-1 receptor in cells. The results showed that they really work — they turn on the signal that is needed to reduce sugar and control appetite.
— We are already working on finding an effective candidate within the framework of the proposed chemotype of compounds with high activity combined with low toxicity. If successful, this will allow us to enter preclinical and clinical trials of the drug. If everything goes well, our development can become the basis for a domestic drug available to Russian patients," Roman Ivanov, director of the Scientific Center for Translational Medicine at Sirius University, told Izvestia.
Prospects in the fight against diabetes and obesity
In the course of the research, the first five compounds have already been tested. The scientists wanted to make sure that the new type of compound they had developed actually activated the hormone receptor in cellular tests.
The new Sirius compounds are low—molecular-weight activators of the GLP-1 receptor, the so-called "satiety and sugar sensor", on which modern drugs for the treatment of obesity and type 2 diabetes are based, Albert Rizvanov, head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, told Izvestia.
— Their advantage is in a potential tablet form and a simpler, more technologically advanced chemical structure, which theoretically simplifies large-scale production. If further studies confirm the efficacy and safety, this approach may be suitable for people with type 2 diabetes, obesity or prediabetes. Especially for those who are uncomfortable with injections and need long—term weight and glycemic control support," the expert noted.
As Albert Rizvanov noted, the acclaimed drug Ozempic (semaglutide) is a peptide "twin" of its own hormone GLP—1 and activates the GLP-1 receptor by itself. It does not stimulate hormone production, but mimics its effect.
— Sirius compounds are conceived as non-peptide, low molecular weight agonists of the same receptor. They also act on the GLP-1 receptor directly, but are potentially easier to synthesize and more convenient for oral administration. In fact, the differences are in the chemical nature (peptide vs "small molecule"), routes of administration, and details of the safety profile. At the same time, the "target" and the physiological effect (reduction of sugar, appetite, slowing down gastric emptying) are common," the scientist said.
A similar group of drugs acts on certain GLP-1 receptors, and if the active substance is a protein compound (such as insulin), when ingested, it is destroyed in the gastrointestinal tract and loses activity. It is for this reason that insulin in tablets still does not exist, said Maxim Burikov, head of the Center for Bariatric Medicine at the FMBA in Rostov-on-Don, co-founder of the Slimmer app.
— If we are talking about substances with a simpler molecular structure that also affect receptors, but are not proteins and are not destroyed when passing through the gastrointestinal tract, then theoretically they can act when taken orally. However, their biological activity is usually lower compared to injectable forms," the expert noted.
The emergence of modern domestic safe tableted GLP-1 agonists will increase patient adherence to treatment, and simplification of production technology will make the drug more accessible to the healthcare system, said the Director of Healthcare Economics at R-Pharm.
However, in any case, it is necessary to wait for the testing of candidate compounds on animals and humans, which may take many years, experts noted.
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