Ozempic Next: 4-in-1 Weight Loss Breakthrough
- Weight loss drugs like ozempic and Wegovy are used by over 15 million adults in the U.S., or 4.5% of the population.
- Now Tufts researchers led by Krishna Kumar, Robinson Professor of Chemistry, have designed a new, next-generation compound with hopes that it could be more effective with fewer side...
- While weight loss drugs currently on the market and in advancement target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat,...
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Next-Generation Obesity Drug Targets Fourth Hormone for Enhanced Effectiveness and Reduced Side Effects
(Last Updated: October 26,2023)
Weight loss drugs like ozempic and Wegovy are used by over 15 million adults in the U.S., or 4.5% of the population. Despite their effectiveness, they have drawbacks.Their effect may not last after discontinuing use, and side effects including osteoporosis and muscle loss have raised concerns about long-term harms. They also induce nausea, which can make it challenging to stay the course of treatment.
Now Tufts researchers led by Krishna Kumar, Robinson Professor of Chemistry, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society.
While weight loss drugs currently on the market and in advancement target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could possibly further enhance the control strategy.
“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”
How the Drugs Work
After we eat a meal, our gut and brain trigger a hormonal “fuel gauge” that regulates levels of glucose and tells us when we have had enough to eat.
The hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Ozempic uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.
but GLP-1 also acts directly on the brain, making us feel full after having a meal, and it slows down the rate that the stomach contents are emptied into the intestines, creating a more evenly paced release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.
It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”
A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both – what’s called in drug development a chimera. That drug, called Mounjaro or zepbound (the brand names for tirzepatide), has the added benefit of substantially reducing nausea. As a more tolerable treatment, it may overtake Ozempic in the weight loss market.
“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raise