The perils and promise of GLP-1 medications

Ozempic and Wegovy, Mounjaro and Zepbound. These GLP-1 agonists and others—originally approved by the U.S. Food and Drug Administration in 2005—have been all over the media, by turns called wonder drugs and cautionary crazes. Penn’s School of Nursing is on the cutting edge when it comes to the study of GLP-1s and has been for years, uncovering myriad ways these medications impact the body, as well as new applications for their use.

While the original intent for GLP-1 medications was for diabetes care, its efficacy as a weight management drug means that researchers like Colleen Tewksbury, assistant professor in nutrition science, are looking closely at how people take it as a treatment for overweight and obesity—for instance, the medication’s impact on micronutrient deficiencies resulting from weight loss. Little to no evidence currently exists in that area, and Tewksbury aims to fill this research gap.

Tewksbury and her team are analyzing dietary quality data, and studying the micronutrient changes associated with rapid weight loss that can be seen in patients on GLP-1 medications. Micronutrients are important for overall health, as well as cognitive and physical function, and deficiencies can result in the development of illness or injury, according to the U.S. Centers for Disease Control and Prevention.

“With the use of these medications for weight loss being so new, no solid recommendations for nutrition care during treatment currently exist,” says Tewksbury. For patients who receive bariatric surgery, monitoring is a key component of their ongoing care. Because GLP-1 medications are self-administered and can result in weight loss without behavioral modifications, patients may achieve their desired goals for weight but be placing other aspects of their health at risk.

Referencing existing data from weight loss associated with sleeve gastrectomy bariatric surgery, Tewksbury’s team is assessing patients’ dietary quality and blood samples to understand changes in iron, calcium, parathyroid hormone, and vitamins D, B1, and B12.

“Our goal is to make sure that if patients are experiencing rapid weight loss, they are doing so safely, and we want to understand what their nutritional support needs may be during this process,” says Tewksbury.

Understanding the side effects

As with any medication, there can be side effects. With GLP-1s, the most common are nausea and vomiting, which can be obstacles to treatment, dosing, and medication adherence. These side effects are the focus of Bart C. De Jonghe, professor of nutrition. He’s investigating why these medications, meant to improve a patient’s state of health, can often make them ill.

“The side effects of any medication are going to impact how long a person stays with their course of treatment,” says De Jonghe. “This is why it is not only important to understand how a medication brings about its intended result, but also why it may cause unintended or undesirable side effects.”

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De Jonghe and his colleagues were among the first researchers to study GLP-1s. Over the past 15 years, they’ve published approximately two dozen papers on this class of medications. The work of his laboratory not only centers on why their use can cause nausea and vomiting but also on unlocking the mechanisms by which GLP-1s reduce weight. The research over the last several years, and continuing, has refined existing treatment uses for GLP-1s and also created new ones.

“The core of my own philosophy on drug therapeutics is that we should strive to produce treatments with zero side effects,” says De Jonghe. “It’s a lofty goal, but we need more drugs to effectively treat diseases without also compromising the patient’s quality of life in the process.”

Looking to the future

Future applications for GLP-1 medications include more than just weight loss. Researchers have linked the drugs to potentially lowering the risk of diabetic kidney disease; decreasing the risk of developing cancers including breast, bowel, pancreatic, and ovarian; and even slowing Parkinson’s Disease. Experts in substance use disorders (SUDs) at the University of Pennsylvania are also looking to GLP-1 medications as a possible way to prevent relapse in people with substance use disorders (SUDs).

Heath D. Schmidt, professor of nursing, is a pharmacologist and neuroscientist studying how chronic exposure to addictive drugs such as cocaine, nicotine, and opioids changes the brain to produce compulsive drug-taking and drug-seeking behaviors. Schmidt and his team are currently researching how GLP-1s can influence the brain to reduce addiction-like behaviors in rodent models.

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“Research scientists in a university setting are often the ones who have the biggest impact on the future of medicine,” says Schmidt. “They create and execute pre-clinical research that ultimately guides the development of new pharmacotherapies and clinical approaches.” He and his team are contributing to the future of GLP-1s by seeking to understand how the medications can regulate the brain’s reward center, while also minimizing some of the unpleasant side effects.

Addictive drugs hijack reward circuits in the brain, leading to increased dopamine levels and compulsive behaviors. Schmidt’s hope is that by interrupting these reward signals, GLP-1 medications can help a patient stop or reduce craving-induced relapse during withdrawal.

However, long-term effects of GLP-1 use over a span of years, or even decades in some cases, are unknown. “Even with the potential clinical benefits we are seeing in early trials for addiction and substance use, it is important to proceed with caution, since much of what is being discussed about GLP-1 medications is anecdotal, and not yet evidence-based,” says Schmidt.

As these three Penn Nursing pioneer-scientists continue to forge new paths with GLP-1 agonists, the potential they have to shape the use of these medications sets the stage for ongoing groundbreaking advancements—related to GLP-1s and beyond—and highlights the promise of Penn Nursing faculty research in unravelling complexities to ensure a healthier future.

This story is by Madeleine Kates and was originally published in the spring 2025 issue of University of Pennsylvania School of Nursing Magazine.