In a groundbreaking discovery, Stanford researchers have identified a naturally occurring molecule that mimics the effects of semaglutide—best known as Ozempic—offering a potential alternative for appetite control and weight loss.
Since its introduction in 2017, Ozempic has gained widespread attention not only for aiding weight loss but also for its various health benefits, such as reducing the risk of kidney failure, easing osteoarthritis pain, and even helping curb alcohol addiction. However, its extensive effects on multiple organs, including the gut and pancreas, have led to side effects ranging from nausea and dizziness to severe conditions like pancreatitis and gallbladder disease. Some reports have even linked the drug to an increased risk of suicidal thoughts and a rare form of blindness known as an “eye stroke.”
To develop a safer alternative, Stanford researchers turned their focus to prohormones—inactive protein molecules that become functional when broken down into smaller peptides. Using a specialized algorithm called Peptide Predictor, they screened thousands of genes to identify potential candidates, ultimately uncovering BRP, a 12-amino-acid peptide with significant effects on the brain’s neuronal activity.
“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas, and other tissues,” explained Katrin Svensson, assistant professor of pathology and co-author of the study. “That’s why Ozempic has widespread effects, including slowing digestion and lowering blood sugar. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
To test BRP’s effectiveness, researchers conducted experiments on both mice and minipigs—chosen because their physiology closely resembles that of humans. A single injection of BRP reduced food intake by up to 50% within four hours in both species. In obese mice, daily injections over 14 days resulted in a notable weight loss of approximately three grams (0.1 oz), primarily from fat reduction, while also improving glucose and insulin tolerance.
Most importantly, the team observed no significant side effects, as the animals exhibited normal water intake, fecal production, and behavior, with no signs of anxiety or distress.
Encouraged by these results, Svensson has co-founded a company to move BRP toward human clinical trials, with the next step being prolonging the peptide’s effects to simplify dosing for potential human use.
“The lack of effective drugs to treat obesity in humans has been a problem for decades,” Svensson remarked. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if it is safe and effective in humans.”
With clinical trials on the horizon, BRP could represent a major breakthrough in weight-loss treatments. If successful, this discovery could pave the way for a new, targeted approach to managing obesity.
The study has been published in Nature.
