Weight -loss drugs such as ozapic and vegovi are used by more than 15 million adults or 4.5% population in the US. Despite their effectiveness, they have shortcomings. They may not have an effect after stopping use, and side effects, including osteoporosis and muscle loss, have increased concerns about long -term damage. They also inspire nausea, which can make it difficult to persist during treatment.

Now the researchers of Tufts led by Robinson Professor of Chemistry, Krishna Kumar have designed a new, next generation complex with hope that it can be more effective with less side effects, which they report in a paper Journal of the American Chemical Society,

While weight loss drugs are currently related to glucose metabolism and desire to eat in the market and in the growth target, the Tufts have identified a fourth target that can potentially further enhance the control strategy.

Obesity is associated with over 180 different disease conditions, including cancer, heart disease, osteoarthritis, liver disease and type 2 diabetes, and affects over 650 million people worldwide. The one who drives us is that we can design the same drug to treat obesity and at the same time reduce society to reduce the risk of developing a long list of health problems. ,

Krishna Kumar, Robinson Professor of Chemistry, Tufts University

How to work drugs

When we eat, our intestine and brain triggers a hormonal “fuel gauge” that controls glucose levels and tells us that when we have enough to eat.

Hormone Glucagon-Sete peptide 1 (GLP-1) is released to help encourage the production of insulin and help in the muscles and other tissues. Now with fuel -filled cells, the level of glucose in the blood becomes normal. Ozapic Uses GLP-1 with minor amendments to increase its availability in the bloodstream. Its success in controlling blood sugar has inspired the American Diabetes Association to recommend it and other GLP -1 -based drugs as a new first line injection treatment for diabetes, beyond insulin.

But GLP-1 also works directly on the brain, which makes us feel complete after meals, and it slows down the rate that the stomach contents are emptied into the intestines, leading to more equally release of nutrients and glucose. Therefore, it has also become extremely popular as a treatment for weight loss.

This is still not a perfect drug strategy for weight loss, though. Kumar said, “The biggest problem with GLP -1 drugs is that they have to be injected once a week, and they can inspire the very strong feeling of nausea.” “40% of people using these drugs accept defeat after the first month.”

A second hormone released after meals is insulinotropic peptide (GIP) dependent on glucose. It makes us feel complete even after meals. GIP looks like GLP-1, so instead of administering two drugs, researchers created a peptide that incorporates structural elements of both, both called drug development A chimera. The drug, which is called Maunjaro or Zepbound (brand name for tirzepatide), has an additional advantage of reducing nausea. As a more tolerable treatment, it can overtake the ozmpic in the weight loss market.

“And then a third hormone, glucagon,” said Kumar. “Contrariously, it actually increases blood sugar, but at the same time increases the cost of energy in the body’s cells, increases body temperature, and suppresses hunger.” By adding glucagon to the mix, GLP -1 and GIP neutralized their glucose -growing effects, leaving the remaining functionalities of all three hormones working together to increase weight loss.

Glucagon is also the same in the composition of GLP -1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognized by their three different receptors. This drug, called retortrudide, currently is in clinical trials that indicate more obtained more than the original GLP -1 drugs (6–15%) than the weight loss (up to 24%).

Going to the gold standard of weight loss with a fourth goal

Kumar said, “The goals that people are trying to shoot is bariatric surgery.” It is a surgical process that reduces the size of the abdomen, which can achieve long -lasting weight loss by up to 30%. “For persons with persistent obesity and potentially affiliated conditions, it becomes an essential but aggressive treatment.”

Current injectable weight loss drugs still decrease with that gold standard, so the tufts chemists focus on a drug redigation that can match the result of weight loss 30%.

“There is another hormone that we wanted to bring to complete a weight control quartet,” said a graduate student at Kumar Lab and prominent writer of the study, Triston Dinsmore, “said Triston Dinsmore, a graduate student at Kumar Lab and lead author of the study. “It is called peptide yy (Pyy). This molecule is also secreted by the intestine after eating food, and its work is to reduce hunger and slow down the process of emptying the food from the stomach, but through various mechanisms compared to GLP-1 or GIP. It can also be included in ‘burning of fat’ directly.

The Pyy is from a separate and structurally unrelated class of hormones compared to the first three, so it combines its structure in a cimely peptide that also mimics GLP-1, GIP and Glucagon. Instead, the Tufts team was capable of joining the two peptide segment end-end, making a new ‘Tetra functional’ clinical candidate.

“One of the boundaries of current drugs is that individual differences, possibly involving how people express target receptors or respond to their respective hormones, may be less than the results of the desired weight loss in many patients,” Martin Beenborn said, visited a scholar in the Chemistry Department. “By killing four separate hormone receptors at the same time, we expect to improve the possibility of average of such variation towards the goal of achieving more and more consistent overall effectiveness.”

“Another issue is that patients have to gain weight after closing the currently available GLP -1 related drugs,” beinborn said, who notes that lifestyle changes should ideally be a complement for drug treatment. This two-dimensional approach will not only support and support someone’s targeted weight, but can also help preserve bone and muscles.

“Recent studies indicate that the weight rebound after the dissolution of the drug is delayed with new, more effective GLP -1 mimatics,” he said. “Extending this observation, one can guess that multi-chims on the lines of one found by us can reach us close to permanent weight loss bariatric surgery standard.”