Georgia State University researchers are making progress in the study of GLP-1-based weight loss treatments, as these medications gain popularity in the United States. A recent poll indicates that about one in eight adults are using drugs such as Ozempic or Wegovy for weight management or chronic health conditions, with usage expected to increase.
Eric Krause, a professor of neuroscience and Georgia Research Alliance distinguished investigator at Georgia State, is leading research focused on how GLP-1 therapies impact brain pathways related to weight loss and muscle mass. “GLP-1 drugs, especially the next-generation versions, are remarkably effective at helping people lose weight,” Krause said. “As more Americans use them, we’re learning more about their benefits and their drawbacks, and that opens the door to making these treatments even better.”
Krause’s research has shown that while GLP-1 receptor agonists reduce interest in high-fat foods and result in rapid losses of body weight and fat, they also cause a reduction in muscle mass. He noted another concern: “And perhaps even more striking was what happened when treatment stopped: The subjects began overeating almost immediately and regained the lost weight — sometimes even more than before.” This observation aligns with patterns seen among patients using these medications.
To address these challenges, Krause’s team is examining how GLP-1 drugs interact with the body’s stress response system. Their studies found that these medications activate the hypothalamic pituitary adrenal (HPA) axis—responsible for producing stress hormones like cortisol—which can be linked to muscle loss and increased eating due to stress.
In collaboration with Dr. Todd E. Golde from Emory University, they developed an antibody therapy called anti-CRH designed to block corticotropin releasing hormone (CRH), thereby reducing stress hormone levels. According to Krause: “Combined treatment (GLP-1 drug + anti-CRH) produced greater weight loss — and importantly, better weight loss quality, meaning more fat loss and less muscle loss.” He added that continuing anti-CRH after stopping GLP-1 helped maintain lower body weights in animal models.
Krause explained this approach as novel because it targets CRH directly rather than its receptors—a strategy he described as potentially having significant promise for metabolic disease treatment.
The research group has created a humanized version of anti-CRH suitable for potential clinical testing. Krause said: “The next step is a Phase 1 clinical trial… We’re actively working to build those partnerships so we can determine whether anti-CRH will be effective and safe in human patients.”
Researchers are also investigating other possible uses for GLP-1-type therapies beyond weight management. Early findings suggest potential benefits for substance-use disorders including alcohol-use disorder—and possibly opioid and nicotine addiction—because GLP-1 receptors exist within reward pathways of the brain.
Looking ahead, Krause anticipates that therapies targeting the GLP-1 system will become standard care for obesity and type 2 diabetes over the next decade. He expects future strategies will combine medication with supportive interventions such as strength training or combination therapies like anti-CRH to help preserve muscle mass during treatment.
Krause credited collaboration within Georgia State’s Center for Neuroinflammation and Cardiometabolic Disease—including faculty members Drs. Jéssica Matheus de Sá, Karen Scott, Annette de Kloet, Javier Stern—as well as staff scientists and students with driving this research forward.
He highlighted student involvement: “When they start… by the time they graduate they’re experts in technical approaches… So seeing the students go through that progression is amazing and it’s one of the best parts of the job.”
