A new class of weight-loss treatments has transformed obesity care, helping people lose amounts once thought achievable only with surgery. Injections such as Ozempic, Wegovy and Mounjaro mimic the gut hormone GLP-1 to suppress appetite, but they can cause side effects in some people, including nausea, vomiting, diarrhea, abdominal pain and constipation.
Researchers at Stanford Medicine have identified a 12–amino-acid peptide called BRP that may offer weight-loss benefits with fewer drawbacks. Unlike GLP-1 mimetics, BRP appears to act mainly in the hypothalamus — the brain’s hunger sensor — rather than primarily stimulating the hindbrain, which is associated with visceral fullness and the nausea often reported with current drugs.
Giles Yeo, professor of molecular neuroendocrinology at the UK Medical Research Council’s Metabolic Diseases Unit, explained that only two brain regions sense circulating hormones because of the blood-brain barrier: the hypothalamus and the hindbrain. “Ozempic and all of these gut hormones have their primary effect through the back of the brain,” he said. The hindbrain drives strong sensations of fullness that can become uncomfortable and provoke nausea, whereas the hypothalamus monitors internal energy state and hunger.
In animal studies, obese mice given daily BRP injections lost weight while untreated mice gained weight. The compound also appeared to reduce fat while sparing muscle, a potential advantage over some GLP-1–type drugs.
The discovery process was notable. Stanford scientists built an AI tool, Peptide Predictor, to scan roughly 20,000 human genes and identify 2,683 candidate hormone-like peptides. They narrowed these to about 100 for testing; BRP emerged as a promising hit. “The sheer audacity to sort through the huge number of peptides is truly breathtaking,” said Randy J. Seeley, professor of surgery at the University of Michigan.
Katrin Svensson, senior author of the Stanford study, has co-founded a company planning human clinical trials in the near future. But experts caution that success in mice doesn’t guarantee human safety and efficacy. Seeley noted that obesity is a chronic condition requiring long-term treatment, so candidate drugs must have strong safety profiles to be viable therapeutics.
GLP-1 drugs are adapted from a natural hormone and can be chemically altered to last longer in the body; BRP could potentially be modified similarly. Even if BRP reaches the clinic, GLP-1–based medicines will likely remain important due to benefits beyond weight loss, such as reducing cardiovascular risk. Still, BRP could offer a valuable alternative, expanding the toolbox for treating a global obesity crisis. “The more tools we have to help us reduce our body weight, the more people are likely to find their personal mix,” Yeo said. “If you’re more likely to stay on the drug, you’re more likely to keep the weight off.”