Soaring in popularity, GLP-1 medications — from weekly injections to newly available pills — are rapidly reshaping how Americans think about weight loss. In fact, a recent poll finds 1 in 8 adults are now taking medications like Ozempic or Wegovy for weight loss or chronic conditions, and use is expected to keep rising.
As researchers continue to learn about and refine these treatments, new approaches are emerging in how we view weight management and metabolic health care. One of those researchers is Georgia State University Professor of Neuroscience and Georgia Research Alliance Distinguished Investigator Eric Krause.
“GLP-1 drugs, especially the next-generation versions, are remarkably effective at helping people lose weight,” Krause says. “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 current research explores brain pathways that could protect muscle mass during treatment and new therapeutic strategies that target stress- and hunger-related neurons.
Here, we talk with him about the latest advances in the evolution of metabolic health care and what he sees on the horizon.
GLP-1-based therapies have become such a phenomenon for health and weight loss. What have you learned about them through your research? Any surprises?
One of the biggest surprises was simply how fast and how powerfully these drugs work. In our studies, GLP-1 receptor agonists sharply reduced interest in high-fat, high-calorie foods and led to rapid losses in both body weight and body fat.
What stood out to us, too, was that this weight loss also came with a reduction in muscle. 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 pattern mirrors what we’re now seeing in many patients, suggesting that continued treatment may be necessary to maintain the benefits. Last month, The New York Times published an article that discusses how this phenomenon is playing out in people using these medications.
So, how is your research diving into these effects and how to mitigate them?
We’re now exploring a fascinating connection between GLP-1 drugs and the body’s stress response. Our studies show that GLP-1 receptor agonists strongly activate the hypothalamic pituitary adrenal (HPA) axis — the system that produces stress hormones such as cortisol in humans and corticosterone in preclinical models. Because elevated cortisol is linked to muscle loss and even “stress eating,” this finding immediately drew our attention.
That led us to a key question: If GLP-1 drugs activate the stress system, could reducing that stress make the drugs work better?
To test this, we partnered with Dr. Todd E. Golde at Emory University to develop an antibody therapy called anti-CRH. It’s designed to calm the body’s stress-hormone network by blocking CRH, a molecule that initiates the stress response.
Two discoveries emerged: 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. Even more exciting, when we discontinued the GLP-1 drug but continued anti-CRH, the mice maintained their weight loss, largely because they naturally ate less.
That second finding suggests that lowering stress hormones may actually help reset the brain to defend a lower body weight, which could be transformative.
Can you explain how this research work is different from what’s currently being done and how it might impact the issue of muscle loss?
Our approach centers on a highly specific antibody we call anti-CRH. It binds to and neutralizes corticotropin releasing hormone (CRH), a key molecule that activates the body’s stress response system. By blocking CRH, we can lower circulating stress hormones like corticosterone.
This represents a new biological approach. Earlier therapies targeted the receptors for CRH or corticosterone, but they didn’t actually lower stress hormone levels themselves. Some researchers consider our strategy — essentially “immunizing against stress” — an outside-the-box way to address metabolic disease. We think it’s an avenue with a lot of potential.
You’ve filed a provisional patent application for your new approach to preserving muscle mass during treatment. What are the next steps for translating this discovery from the laboratory to potential human therapies?
Our group has created a humanized version of anti-CRH, meaning it’s ready for potential testing in people. The next step is a Phase 1 clinical trial, which is a significant and resource-intensive milestone that requires an external partner. We’re actively working to build those partnerships so we can determine whether anti-CRH will be effective and safe in human patients.
Are there other health benefits future GLP-1-type treatments might offer besides weight loss?
Researchers are now exploring GLP-1 drugs as potential treatments for substance-use disorders. Some of the strongest early results are in alcohol-use disorder, which makes sense, as these drugs decrease caloric intake and alcohol carries calories.
Even more intriguing, emerging evidence suggests possible benefits for opioid and nicotine addiction. GLP-1 receptors are present in the brain’s reward pathways, which raises the possibility that these drugs might reduce not only overeating but also other compulsive or reward-seeking behaviors.
What’s next? What questions are researchers still trying to answer about GLP-1-based medications and long-term health?
As more patients take these drugs, we are finding more about their benefits and drawbacks. Some key questions include:
- How do GLP-1 medicines and rapid weight loss affect muscle mass and strength?
- What cardiovascular benefits are due to the drug itself versus the weight loss?
- Could GLP-1 drugs protect brain health or reduce the risk of Alzheimer’s disease?
With all these lines of inquiry, I think it will be important to determine how much of the benefit comes directly from GLP-1R therapy itself, and how much is actually secondary to the weight loss it causes.
Look 10 years ahead in this type of health care and weight management. What do you see?
I expect that therapies targeting the GLP-1 system will become a standard part of treating obesity and type 2 diabetes. They’ll likely be paired with supportive strategies such as strength training or combination therapies like anti-CRH to help preserve muscle.
Ultimately, most patients taking these medications discontinue treatment because of side effects or financial concerns, which puts them at risk to regain the lost weight. I think we’ll see that health care providers will investigate ways to better transition patients off these medications and onto interventions that help keep the weight off.
Tell us about the team you work with here Georgia State. How has collaboration shaped this research?
I’m part of a conglomerate that is made up of the talented members of the GSU Center for Neuroinflammation and Cardiometabolic Disease. In particular, the project is led Drs. Jéssica Matheus de Sá and Karen Scott in collaboration with Drs. Annette de Kloet and Javier Stern. Our research team is a mixture of faculty members, staff scientists, postdoctoral fellows and graduate and undergraduate students.
Working with the students is especially rewarding. When they start, some have never stepped foot in an academic research laboratory, and by the time they graduate they’re experts in technical approaches that are like something out of a science fiction novel, and they’ve developed their own ideas and hypotheses. So, seeing the students go through that progression is amazing and it’s one of the best parts of the job.
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