Researchers at Pennsylvania State University have unveiled a new class of peptide compounds designed to curb weight gain by shrinking stomach capacity, a method aimed at delivering weight loss levels comparable to bariatric surgery but without triggering the nausea and vomiting commonly associated with many weight‑loss and diabetes medications. These findings were shared at a major ACS Spring conference, highlighting progress in the pursuit of safer, noninvasive weight management options.
Gastric bypass and similar procedures can produce durable weight loss for individuals dealing with obesity and can even lead to remission of type 2 diabetes. Yet these surgeries carry surgical risks, eligibility restrictions, and long‑term considerations that make them unsuitable or undesired for many patients. In contrast, drugs that suppress appetite—particularly those targeting GLP‑1 and PYY pathways—have shown promise in reducing food intake and improving metabolic control. However, a large portion of patients discontinue these medications within the first year due to side effects such as nausea and vomiting, which can undermine long‑term success.
In response to this challenge, the researchers developed a peptide, designated GEP44, engineered to activate two receptors for the PYY peptide along with one receptor for GLP‑1. In preclinical tests, mice with obesity reduced their food intake by about 80 percent compared with normal controls. Over a 16‑day period, these animals achieved an average weight loss near 12 percent, a rate that surpassed outcomes observed with GLP‑1 alone by a threefold margin. The results point to a potential combination therapy that more effectively curbs appetite while supporting metabolic balance.
Remarkably, experiments conducted with shrews—a mammalian model capable of vomiting—showed no signs of nausea or emesis in response to GEP44, a finding that helps address one of the most significant drawbacks of existing antiobesity therapies. This difference between species suggests the possibility of a more tolerable safety profile in humans, though researchers emphasize that human studies are necessary to confirm tolerability and efficacy beyond animal models.
Beyond weight reduction, scientists noted that GEP44 might influence energy expenditure, potentially increasing the calories burned even without proportional increases in activity. In addition to lowering blood glucose levels, the compound appeared to dampen cravings for opioids in tested animals. If these effects translate to people, such a drug could offer a dual benefit by aiding weight management while reducing vulnerability to opioid cravings, which has profound implications for addressing substance use disorders in tandem with metabolic health.