Wegovy, eat your heart out. In a new research paper, scientists say they’ve discovered a naturally occurring hormone that might help people lose weight while avoiding the side effects commonly associated with semaglutide (the active ingredient in Ozempic and Wegovy) and similar drugs.
A team of researchers at Stanford Medicine conducted the study, published last week in the journal Nature. With the help of artificial intelligence, the team identified a previously unknown peptide that appeared to safely reduce the appetite and weight of mice and miniature pigs without causing nausea or other gastrointestinal symptoms. More studies will be needed to verify the molecule’s safety and effectiveness in people, but the findings provide a tantalizing preview into what could be the future of obesity treatment.
The emergence of semaglutide and similar drugs in recent years has been truly revolutionary for the field of obesity medicine. These medications, also used for type 2 diabetes, have proven to be far more effective at helping people lose weight than diet and exercise alone, with results ranging from 15% to 20% lost weight in clinical trials. Semaglutide works by mimicking GLP-1, a hormone that helps regulate our appetite and metabolism, among other functions (some drugs like tirzepatide mimic both GLP-1 and other related hormones).
As groundbreaking as these drugs are, they are known to commonly cause annoying GI symptoms, and may rarely cause more severe complications like gastroparesis (stomach paralysis). Scientists have also been working to find and develop newer generation drugs that could provide even greater weight loss or offer other conveniences, such as being available as a pill. In that vein, the Stanford Medicine researchers devised a novel strategy to find their drug candidate.
Many hormones in the body are activated only when their precursors are cleaved by specific enzymes. These precursors are called prohormones, and the family of enzymes that chop them up are called prohormone convertases. The researchers looked at one of these enzymes, prohormone convertase 1/3, which is known to help produce GLP-1. They decided to see if they could find other useful hunger-related hormones naturally produced by the enzyme. To greatly speed up this discovery process, they developed a computer algorithm (nicknamed Peptide Predictor) to narrow the list of potential molecules that fit their criteria.
This screening found an initial batch of 373 prohormones that could yield some 2,700 different peptides (peptides are often the building blocks of larger proteins, but they can have their own distinctive functions in the body). From there, the researchers tested 100 peptides they knew or suspected could affect the brain’s hunger drive (including GLP-1 for comparison). And ultimately, they identified one molecule that appeared to be particularly promising, a 12 amino acid-long peptide called BRINP2-related peptide, or BRP.
The scientists then tested BRP on lab mice and miniature pigs (minipigs are thought to closely resemble people metabolically). They found that a single dose of BRP greatly reduced the appetite of both animals in the short term, sometimes by as much as 50%. And obese mice given BRP significantly lost weight over a two-week span, with most of this weight being stored fat.
Further experiments showed that BRP’s hunger-reducing effects on the brain don’t involve the GLP-1 receptor at all, and it simply didn’t cause the animals to experience the GI symptoms commonly associated with Ozempic-like drugs. The dosed animals also didn’t experience changes to their movement, level of anxious behavior, or water intake, suggesting that BRP can be safely tolerated when taken as a drug.
“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues. That’s why Ozempic has widespread effects including slowing the movement of food through the digestive tract and lowering blood sugar levels.” said study senior researcher Katrin Svensson, an assistant professor of pathology at Stanford, in a statement from the university. “In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
The team’s findings are, of course, preliminary at this point. It will take plenty more time and research, including early successful clinical trials in humans, before BRP should be seen as the next big thing in obesity treatment. But the team’s discovery is the latest to suggest that semaglutide has truly sparked a sea change in obesity treatment. There are now dozens of experimental drugs in the pipeline that are threatening to rival or even surpass Ozempic/Wegovy, including different formulations of semaglutide. For their part, Svensson and her colleagues have already filed patents on BRP, and she has co-founded a company that she hopes will develop the molecule for clinical use.
No drug comes without side effects, but the future of obesity treatment could someday involve a lot less nausea.
