GLP-1–based therapies, popularized by medications like semaglutide and tirzepatide, are reshaping the way we think about obesity, metabolic health, and even chronic disease prevention. While these drugs first gained widespread attention for supporting significant weight loss, new research shows their influence reaches deep into multiple body systems.
At UC Davis Health, experts are taking a comprehensive look at how GLP-1 medications affect the entire body, from the gut and brain to the heart, muscles, and bones. Their findings point to a future where obesity treatment is not only more effective but also more holistic.
According to Miranda Stiewig-Rapp, assistant professor of endocrinology at UC Davis Health and incoming director of the system’s new Obesity Clinic (opening in 2026), GLP-1 agonists are redefining what’s possible in medical weight management.
Early clinical trials show average weight loss of 15-20%, compared to the 5-10% typically achieved with earlier generations of medication. And while these drugs offer powerful support, experts emphasize that pairing them with lifestyle changes creates the strongest outcomes.
The systemic impact of GLP-1 therapies
UC Davis Health recently brought together leading scientists, clinicians, researchers, and industry innovators to examine how GLP-1 drugs influence the body as a whole. Their findings reveal broad metabolic shifts that reinforce the importance of personalized nutrition, fitness, and long-term support.
The gut
GLP-1 slows gastric emptying, a mechanism that helps regulate blood sugar and prolong satiety. But it also influences the trillions of microbes that make up the gut microbiome.
These medications change how food moves through the digestive tract and alter fermentation patterns — shifts that can reshape the microbiome itself. A healthier microbiome can improve insulin sensitivity and support the metabolic benefits of GLP-1 therapies.
However, gastrointestinal side effects such as nausea, vomiting, or diarrhea remain common as the body adjusts. Supporting gut health with probiotics, fiber, and nutrient-dense meals can help minimize discomfort.
The brain
GLP-1 signals travel to the brain through the bloodstream and vagus nerve, reducing hunger and quieting the persistent “food noise” many patients describe.
Emerging research suggests that GLP-1 therapies may also influence reward pathways, potentially affecting cravings for sweets, fatty foods, and even substances like nicotine or alcohol. With appetite and reward signaling both shifting, many patients find it easier to adopt healthier eating patterns.
The muscles
While GLP-1 medications promote fat loss, rapid weight reduction may also lead to a loss of lean mass. Experts note that 15-25% of weight lost during calorie reduction — whether through medication or diet — can be lean mass.
Maintaining physical activity and prioritizing high-quality protein are essential for preserving muscle and keeping metabolism strong. Resistance training and structured exercise plans remain important companions to GLP-1 therapy.
The bones
Bone is metabolically active and responds to hormonal shifts, including those influenced by GLP-1. Rapid weight loss, reduced food intake, and nutrient gaps can place extra stress on bone density, especially in older adults and postmenopausal women. A balanced diet rich in calcium, vitamin D, magnesium, and protein, along with weight-bearing exercise, helps protect bone strength during GLP-1 therapy.
The heart
Beyond blood sugar control and weight loss, GLP-1 receptor agonists offer significant cardiovascular protection. Clinical trials show they reduce the risk of major heart events such as heart attack and stroke. Multi-agonist medications that combine GLP-1 with GIP or glucagon may enhance these heart benefits even further by improving fat metabolism and reducing inflammation.
Nutrition matters more than ever
Because GLP-1 medications suppress appetite, patients often eat less, which can make it harder to get the nutrients the body needs. Precision nutrition approaches can help close these gaps. The recommendations include choosing smaller, nutrient-dense meals; prioritizing high-quality protein; taking vitamins like B12, D, folate, magnesium, and iron; staying hydrated; and supporting gut health with probiotics and fiber.
Behavioral insights and BrainWeighve
At the 2025 conference on Obesity and Chronic Diseases (ICOCD) in Boston in November, Dr. Robert Pretlow, publisher of Childhood Obesity News, presented emerging insights into how GLP-1 medications interact with behavior, reward, and lifestyle habits. Dr. Pretlow’s core message was clear: GLP-1 medications work best when paired with lifestyle modification.
Dr. Pretlow is the creator of BrainWeighve, a weight loss app for overweight and obese children. In breaking news, Dr. Pretlow announced that the BrainWeighve clinical trial at U.C.L.A. has expanded to include 10 subjects currently taking GLP-1 medications. This addition aims to help researchers understand how lifestyle and behavioral tools can enhance — or possibly even reduce — the need for medication over time.
How GLP-1s affect the reward system
The mechanism of action for GLP-1 agonists is believed to involve the inhibition of reward cues, which may reduce cravings and compulsive eating behaviors. This could help “quiet” displacement mechanisms — behaviors people use to soothe emotional or psychological discomfort through food.
But a key question remains: What happens if displacement is never addressed?
According to Dr. Pretlow, pairing displacement interventions with GLP-1 therapy may allow patients to use lower doses of medication, support tapering off GLP-1s over time, help non-responders gain better results, and provide long-term tools for managing eating addiction and emotional hunger.
These early findings suggest that displacement activities — redirecting urges into harmless or productive behaviors — may offer meaningful support to individuals struggling with overeating.
The BrainWeighve study
These concepts are at the heart of BrainWeighve, a behavior modification and weight loss app currently in clinical trials at UCLA. The program is designed for obese teens and uses a self-directed, physician-supervised approach to tackle overeating one “problem food” at a time.
By helping participants rechannel emotional urges into healthier coping mechanisms, BrainWeighve aims to support sustainable weight loss — and reduce dependence on willpower alone.
As Dr. Pretlow summarized in his presentation:
Displacement activity may provide individuals with hope that they can curb overeating without relying entirely on medication or willpower.
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Source: “UC Davis Health examines systemic impact of GLP-1–based therapies,” UC Davis Health, 12/5/2025
Source: “Treatment of Eating Addiction and Obesity As Displacement Activity: A Pilot Study,” ICOCD presentation, 11/7/25
Image by Dr. Pretlow
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