If you’re considering taking a GLP-1 medication for weight loss, you’ve probably heard of the two leading brands in the space: Wegovy and Zepbound. (Ozempic and Mounjaro are also GLP-1s, but are designed and primarily prescribed for those with Type 2 diabetes.) Here, get key insights from educators affiliated with each company and a leading internist who prescribes these medications regularly, so you can decide which option is best for you.
Featured Experts
- Dr. Amanda Kahn, a board-certified internist and longevity expert
- Dr. Luis-Emilio Garcia, vice president of Global Medical Affairs and Cardiometabolic Health at Eli Lilly and Company
- Dr. Jason Brett, principal U.S. medical head at Novo Nordisk
Why Is Everyone Talking About GLP-1s Right Now?
“In the U.S. alone, more than 110 million people are living with obesity, and by 2030, cardiometabolic diseases like obesity, diabetes and cardiovascular disease could affect one third of adults globally,” says Dr. Luis-Emilio Garcia, vice president of Global Medical Affairs and Cardiometabolic Health at Eli Lilly and Company, the parent company of Zepbound. “For many people with obesity, lifestyle modifications alone—diet, exercise, behavioral counseling—may not result in sufficient and sustained weight reduction.” That’s where GLP-1 medications come into play.
“GLP-1s have completely transformed the landscape of weight management and metabolic medicine,” says Dr. Amanda Kahn, a board-certified internist and longevity expert. “For the first time, we have a therapy that not only helps people lose significant amounts of body fat, but also does so by targeting the root biological causes of overeating, insulin resistance and inflammation rather than relying on solely on lifestyle modification and willpower. From a longevity standpoint, their influence goes far beyond the scale. These medications reduce chronic inflammation, improve insulin sensitivity, support vascular health, and reduce the long-term risk of diabetes, cardiovascular disease dementia and even some cancers. They mimic natural hormones released after eating, helping regulate blood sugar, appetite and digestion, but they also appear to influence inflammatory and hormonal pathways linked to aging and disease.”
The Key Differences to Know About When Considering a GLP-1
“Semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) are both powerful tools in this new era of metabolic medicine, but they work a bit differently,” says Dr. Kahn. “Semaglutide is a pure GLP-1 receptor agonist that mimics the body’s natural GLP-1 hormone. This hormone slows digestion, improves satiety and balances blood sugar. Tirzepatide is a dual agonist that acts on both GLP-1 and another hormone called GIP.” Below, we explore the key differences between them.
What is Wegovy?
“Wegovy is an FDA-approved prescription medicine used alongside a reduced calorie diet and increased physical activity to help people living with obesity reduce excess body weight and maintain weight reduction long-term,” says Jason Brett, MD, principal U.S. medical head at Novo Nordisk, the parent company of Wegovy. “It works by mimicking a naturally occurring hormone in the body called GLP-1—glucagon-like-peptide1—which helps regulate appetite. By acting on appetite control centers in the brain, Wegovy helps people eat fewer calories and lose weight.”
Wegovy (semaglutide) injection 2.4 mg is FDA-approved, in combination with a reduced calorie diet and increased physical activity, to:
- Reduce the risk of major cardiovascular events such as death, heart attack, and stroke in adults with known cardiovascular disease and either obesity or overweight
- Help adults and children aged 12 years and older with obesity, or certain adults with overweight who also have weight-related medical problems, lose excess body weight and keep it off
- Treat adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) who have moderate to advanced liver fibrosis
What is Zepbound?
“Zepbound is a once-weekly injection prescription medicine,” says Dr. Garcia. “It is a dual receptor agonist, meaning it targets two receptors—GIP and GLP-1—found in areas of the human brain that are important for appetite regulation. Zepbound reduces appetite, food intake, body fat and body weight. By targeting both GIP and GLP-1 receptors, Zepbound is unlike other incretins approved for obesity management, which target only GLP-1 receptors.” Dr. Kahn adds that because Zepbound also targets GIP, it provides extra benefits for fat metabolism and insulin sensitivity. “This often results in more significant fat targeting with better muscle preservation,” she explains.
Zepbound is available in an autoinjector (a single-dose pen) and a single-dose vial, and is FDA-approved for the treatment of obesity, as well as for moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity. This medication is meant to be prescribed by a doctor as part of a long-term treatment plan, alongside diet and exercise.
What are the side effects of Wegovy and Zepbound?
Both medications share similar potential side effects, which Dr. Kahn says can include mild gastrointestinal symptoms such as nausea, bloating, constipation and/or reflux. “These effects occur because GLP-1s slow gastric emptying and alter gut motility,” she explains. “However, in practice, Zepbound often causes fewer or milder initial GI side effects compared to Wegovy. This is likely due to the addition of the GIP pathway, which appears to modulate digestion more smoothly and buffer some of the nausea or bowel movement changes seen with pure GLP-1 agonists.”
“The gastrointestinal side effects are usually mild to moderate, but sometimes can be severe, and tend to occur early, when starting treatment or increasing the dose,” Dr. Brett adds. “Often, they are transient, meaning they often go away with time.” Dr. Kahn recommends “starting low and titrating slowly, staying hydrated and ensuring adequate dietary fiber, which can help minimize discomfort, as well as working with a provider who is very experienced with the nuances of GLP-1 therapy.” She also says supplementing with vitamin B12 can be beneficial, as GLP-1 medications may slightly reduce B12 absorption over time. “When introduced thoughtfully, most patients tolerate these medications very well and experience only brief adjustment symptoms.”
The Clinical Study Results
Both medications are highly effective, Dr. Kahn says, but clinical studies show tirzepatide (Zepbound) typically produces more substantial results when it comes to weight loss. “On average, patients using tirzepatide lose about 22 to 25 percent of their total body weight, compared to roughly 15 percent with semaglutide [Wegovy],” she explains. The clinical study Dr. Kahn is referencing is the SURMOUNT-5 clinical trial (published in May 2025) of 751 adults with obesity or overweight but without type 2 diabetes. This study directly compared the results of Wegovy and Zepbound on these individuals, and Zepbound led to superior weight reduction compared to Wegovy: 20.2 percent or 50.3 lbs vs. 13.7 percent or 33.1 lbs, respectively.
“Tirzepatide’s dual mechanism, targeting both GLP-1 and GIP receptors, appears to create a more balanced metabolic effect, improving fat burning while better preserving lean muscle,” says Dr. Kahn. With the addition of GIP, we notice fewer of the gastrointestinal side-effects seen with semaglutide. For these reasons, I typically prescribe Zepbound as a first-line agent for a metabolic reset. That said, both medications dramatically reduce insulin resistance, inflammation and cardiovascular risk factors. The choice often depends on individual tolerance, response and personal health goals rather than a simple stronger versus weaker comparison.”
“If a new patient is already doing well on Wegovy and seeing consistent progress, I generally don’t switch them unless they express interest in trying a different approach or if they plateau on their current regimen,” Dr. Kahn continues. “Both medications can be effective when personalized to the individual, but Zepbound tends to offer broader metabolic and longevity benefits overall. Ultimately, I tailor treatment to the individual. Longevity medicine is about personalization.”
Who should and should not take these GLP-1 medications?
“Originally, these medications were developed for people with obesity—a BMI over 30—or those who are overweight—BMI over 27—with related health issues such as high cholesterol or high blood pressure,” explains Dr. Kahn. “However, in longevity medicine, the ideal candidate isn’t always defined by BMI alone. Patients can have a normal BMI but can have a high body fat percentage on body composition testing. I also consider GLP-1s for individuals with visceral fat accumulation, signs of insulin resistance, fatty liver or inflammatory conditions, so even in those who appear lean externally but have internal metabolic or inflammatory imbalances.”
However, Dr. Kahn says there are important exclusions. “People with a history of medullary thyroid cancer, multiple endocrine neoplasia type 2 (MEN2) or severe gastrointestinal motility disorders should not take these medications,” she advises. “They should also be used cautiously in individuals who are already underweight or have a history of disordered eating. The goal is to restore balance and improve metabolic flexibility, not to just push for weight loss, or to take weight loss to an extreme.”
