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Now Tuffs researchers, led by Krishna Kumar, a professor of chemistry Robinson, designed a new complex of the next generation in the hope that it will be more effective with less side effects, which they report in a paper in Journal of the American Chemical Society.

While weight loss medications are currently in the market and in the development goal, two, or even three hormonal receptors related to the representation of glucose and the desire to eat, the TUFTS team set a fourth goal that can enhance the control strategy.

“Obesity is associated with more than 180 cases of different diseases, including cancer, cardiovascular diseases, bone arthritis, liver disease and type 2 diabetes, and affects more than 650 million people all over the world,” Kumar said. “What drives us is the idea that we can design a single drug to treat obesity and mitigate simultaneously from the risk of developing a long list of health problems that society suffers from.”

How do drugs work

After we eat a meal, our intestine and brain provokes the hormonal “fuel scale” that regulates glucose levels and tells us when we have enough to eat.

The Betheed 1 (GLP-1) is launched for hormones to help stimulate the production of insulin and absorb glucose in the muscles and other tissues. With the presence of the cells now loaded with fuel, the level of glucose in the blood is due to normal. OzemPIC GLP-1 is used with slight adjustments to increase its availability in the bloodstream. Its success in controlling the blood glucose level to the American Diabetes Association pushed its recommendation and other GLP-1 drugs as new injection treatments for diabetes, before insulin.

But GLP-1 also works on the brain directly, which makes us feel full after eating a meal, and slows down the rate in which the stomach contents are emptied, which creates more dangerous than nutrients and glucose in the bloodstream. For this reason, it has also become very common as a treatment for weight loss.

It is still not a perfect drug weight loss strategy. Kumar said: “The biggest problem with the GLP-1 drugs is that they should be injected once a week, and they can stimulate a strong feeling of nausea,” Kumar said. “Up to 40 % of people who use these medications surrender after the first month.”

The second hormone that was launched after eating is an insulin -based peptide (GIP). It also makes us feel completely after the meal. GLP-1 is very similar, so instead of managing two properties, the researchers created one peptide that includes structural elements of both-the so-called AH CIMERA development. This medicine, which is called mounjaro or Zepbound (brand names for Tirzepatide), has an additional benefit to reduce nausea significantly. As a more tolerance treatment, OzemPIC may surpass the weight loss market.

Kumar said: “Then there is a third hormone, Glucagon.” “Ironically, it actually increases glucose in the blood, but at the same time increases the spending of energy in the cells of the body, raising the body temperature, and leading to the suppression of appetite.” By adding glucagon to the mixture, the GLP-1 and GIP ends with a neutralization of its glucose effect, leaving the remaining functions of all three hormones that work together to enhance weight loss.

Glucagon is also similar in the structure of the GLP-1 and GIP, so the developers of the drugs have created an illusion with one that merges the elements of all three hormones, which can be recognized by their three separate receptors. This medicine, which is called Retatrudide, is currently present in clinical trials that indicate the largest weight loss (up to 24 %) compared to the original GLP-1 (6-15 %).

Going to the gold standard weight loss with a fourth goal

Kumar said: “The goal of people is trying to shoot him is obesity.” This surgical procedure greatly reduces the size of the stomach, which can achieve long -term weight loss of up to 30 %. “For individuals with persistent obesity and potential deadly conditions, it becomes necessary but invasive treatment.”

Current weight loss medications are still injected by this golden standard, and thus TVTS chemists focus on the redesign of drugs that can correspond to the results of weight loss by 30 %.

“There is another hormone that we wanted to bring to complete the quadruple weight control,” said Treistan Dennsor, a student of high studies at Kumar Laboratory and the author of the study. “It is called YY (PYY). This molecule is also excreted by the intestine after we have a meal, and its task is to reduce appetite and slow down the process of emptying food from the stomach, but through different mechanisms from GLP-1 or GIP. It may also be involved in burning” fat “directly.”

PYY is a separate category of hormones that are not related to the first three hormones, so mixing its structure in a fantasy peptide that also mimics the GLP-1, GIP and Glucagon was not easy. Instead, the Tuffs team managed to join two parts of peptide from one side, which led to the establishment of a new clinical candidate “Tetra-Funical”.

“One of the restrictions imposed on current drugs is that individual contrast, including how people express targeted receptors or respond to their corresponding hormones, can lead to the results of weight loss less than patients in many patients,” said Martin Pinporen, a visit to the chemistry department. “By hitting four different hormonal receptors at the same time, we hope to improve the average opportunities for this difference towards the goal of achieving a more comprehensive and more consistent effectiveness.”

“The second issue is that patients tend to be overweight after stopping the drugs currently available GLP-1,” said Pinporen, who notes that lifestyle changes should be complementary to drug therapy. This approach of only two types will not support and maintain the target weight, but it may also help in maintaining the mass of bone and muscles.

“Recent studies indicate that the recovery of weight after drug stop is delayed with the latest and most effective GLP-1 simulation,” he said. “It extends from this observation, one can speculate that the multi -project, similar to the one we discovered, can make us closer to the level of obesity surgery for permanent weight loss.”