GLP-1 agonists are reshaping modern health care, delivering benefits that reach far beyond glycemic control and weight loss. 

“These medications are transforming the treatment landscape, dramatically improving the amount of weight loss achievable through medication alone or in combination with lifestyle interventions,” shared Miranda Stiewig-Rapp, assistant professor of endocrinology at UC Davis Health. Stiewig-Rapp is the incoming director of a new Obesity Clinic the health system is set to open in 2026. “In early clinical trials, patients on GLP-1 agonists have achieved weight loss of 15–20%, compared to the 5–10% typically seen with previous medications.”

Holistic approach to GLP-1 drugs

Beyond weight loss, GLP-1 agonists have demonstrated the ability to reduce major cardiovascular events, combat fatty liver disease and alleviate obesity-related complications such as knee pain, sleep apnea, and acid reflux. Emerging research is also exploring their potential effects on the brain, including whether they can help reduce cravings for drugs, alcohol and nicotine.

Despite these promising developments, GLP-1 therapies remain relatively new. The first agent in this class was approved in 2005 for type 2 diabetes, and ongoing studies continue to look at their broader applications, long-term benefits and safety profile.

At UC Davis Health, researchers are taking a holistic approach — examining GLP-1 drugs across multiple systems, from gastrointestinal and cardiovascular physiology to musculoskeletal and neurocognitive function. 

Recently, the institution convened leading scientists, industry innovators and clinical experts to explore the systemic impact of GLP-1–based therapies and their potential to transform patient care.

The gut: More than digestion

GLP-1 has a substantial impact on the gastrointestinal (GI) system. It slows gastric emptying, which helps control blood sugar and prolongs satiety. But the gut is also home to trillions of microbes that influence metabolism. GLP-1 therapies alter the way food moves in the gut and its fermentation patterns. These changes can shift the makeup of the microbiome.

“GI intolerance with GLP-1 RA use is a big deal. Patients might experience nausea, vomiting and even diarrhea. The majority of these symptoms are the effects of GLP-1 RA drugs on the GI tract and the delay in the gastric emptying,” said bariatric surgeon Mohamad Ali, professor and chief of Foregut, Metabolic and General Surgery at UC Davis Medical Center.

A healthier microbiome supports GLP-1 activity and improves insulin sensitivity. Fiber-rich diets and probiotics may also enhance these effects, reinforcing gut health during therapy.

The brain: Appetite and beyond

GLP-1 signals travel from the gut to the brain via the bloodstream and the vagus nerve. These signals reduce hunger and dampen cravings for high-calorie foods. Emerging research suggests GLP-1 may also affect reward pathways, potentially influencing taste perception.

“The patients taking GLP-1 RA medications report that the ‘food noise’ — the constant thinking about food — is quieter,” Ali said.

Appetite suppression helps with weight loss, but it can also change food preferences. Patients often report reduced desire for sweets and fatty foods, creating an opportunity to adopt healthier habits.

The muscles: Preserving strength

Skeletal muscle is the body’s largest site for glucose uptake and a key player in metabolic health. While GLP-1 drugs promote fat loss, rapid weight reduction can lead to 15–25% lean muscle mass loss. Lean muscle mass is the weight of the body that is not fat — including muscles, bones, organs and more.

“We are losing around 20% of muscle mass, but that is not different from diets that restrict calorie intake. Much of the reported 40% lean mass loss with GLP-1 use is coming from the liver,” explained exercise physiologist Keith Baar, a professor of Neurobiology, Physiology and Behavior and Physiology and Membrane Biology. “It is still important for patients taking GLP-1 medication to limit muscle wasting through exercise and high-quality protein.”

Losing muscle can lower metabolic rate and physical strength. Strategies like resistance training and high-quality protein intake are essential to maintain muscle during therapy.

The bones: Hidden risks

Bone is metabolically active and responds to incretin hormones, like GLP-1 and GIP, released in the intestines after eating to stimulate the pancreas to produce insulin. While some evidence suggests protective effects, rapid weight loss and reduced nutrient intake can compromise bone density.

Older adults and postmenopausal women face a higher risk of bone loss. This risk can increase with improper nutrient intake. These groups would need to ensure they are getting adequate calcium, vitamin D and magnesium through their diet as these are critical for bone health. Also, weight-bearing exercise strengthens bones, making them denser and stronger.

The heart: Cardiovascular protection

GLP-1 receptor agonists do more than regulate blood sugar — they also protect the heart. Clinical trials have shown that these medications reduce the risk of major cardiovascular events, including heart attack and stroke.

GLP-1 receptors are found in the heart and blood vessels, influencing blood pressure, lipid profiles, and inflammation. Multi-agonist therapies combining GLP-1 with GIP or glucagon may amplify these benefits by improving fat metabolism and reducing cardiovascular risk even further.

Nutrition matters more than ever

While GLP-1 drugs suppress appetite, they also create new nutritional challenges. Eating less can mean missing out on essential nutrients. Experts recommend precision nutrition strategies:

• Smaller, nutrient-dense meals rich in high-quality protein
• Micronutrient support for vitamins B12, D, folate, magnesium and iron
• Hydration solutions to counter reduced thirst signals
• Fiber and probiotics to support gut health

GLP-1 therapies are revolutionizing obesity and diabetes care, but they also reshape physiology in ways that demand attention. Experts say supporting gut and heart health, preserving muscle, and protecting bone are essential for long-term success. They note that pairing these medications with precision nutrition and lifestyle strategies ensures that weight loss translates into lasting health.

“This shift caused by GLP-1 use is opening new opportunities for food companies to finally build the healthier food system we’ve long imagined," said Justin Siegel, faculty director of the UC Davis Innovation Institute for Food and Health.

For more on the science of metabolic hormones, check UC Davis’ white paper. The paper explores the science at the intersection of metabolic hormones and precision nutrition and multi-target therapies, like tirzepatide and retatrutide.