Researchers at Tufts University have developed a promising new weight loss drug designed to provide more effective results with fewer side effects. The drug, which targets multiple hormone receptors, could offer a solution to the long-standing limitations of current weight loss medications. These medications, including popular drugs like Ozempic and Wegovy, have been effective for many users, helping them lose weight and improve metabolic health. However, they come with significant drawbacks, such as nausea, muscle loss, and osteoporosis, along with the risk of regaining weight after discontinuation.
The Tufts team, led by Krishna Kumar, a Robinson Professor of Chemistry, has focused on improving these treatments by targeting additional hormone receptors involved in appetite regulation and glucose metabolism. Their research, published in the *Journal of the American Chemical Society*, introduces a drug that combines elements of four key hormones. This new compound aims to deliver enhanced weight loss results while minimizing common side effects.
Currently available weight loss drugs, such as those based on GLP-1, target hormones that regulate glucose levels and hunger. GLP-1 helps control blood sugar by stimulating insulin production and making users feel full after meals. However, these drugs require weekly injections and often induce nausea, leading to high rates of treatment discontinuation. Other medications like tirzepatide, which combines GLP-1 with another hormone, GIP, have shown promise by reducing nausea and improving weight loss outcomes. But even these drugs do not achieve the same level of weight loss seen with bariatric surgery, which can result in up to 30% weight loss.
The Tufts team’s new drug goes a step further by incorporating a third hormone, glucagon, which increases energy expenditure, raises body temperature, and suppresses appetite. The combined effects of GLP-1, GIP, and glucagon lead to greater weight loss, as demonstrated by early clinical trials of a drug called retatrudide. The research team is now focused on adding a fourth hormone, peptide YY (PYY), to the mix. PYY, which also reduces appetite and may aid in fat burning, could further improve weight loss outcomes by targeting four distinct hormone receptors.
By addressing multiple hormonal pathways at once, the Tufts researchers hope to achieve more consistent results across patients, overcoming individual variations that may limit the effectiveness of current treatments. The ultimate goal is to create a drug that can rival the success of bariatric surgery without the need for invasive procedures. Early trials suggest that the new compound could offer up to 24% weight loss, surpassing the typical 6-15% weight loss achieved with existing GLP-1 drugs.
The team’s work marks a significant step forward in the quest for more effective and sustainable weight loss solutions. With ongoing research and development, this new approach could provide a valuable alternative for people struggling with obesity, offering a less invasive and more accessible option to achieve long-term weight management and reduce the health risks associated with excess weight.
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