Considering taking a GLP-1 medication for weight loss? You’ve likely heard of the leading brands: Wegovy and Zepbound. (Ozempic and Mounjaro are also GLP-1s, primarily for those with Type 2 diabetes.) Learn from educators affiliated with each company and a leading internist who prescribes these medications regularly to decide which option is best for you.
Featured Experts
- Dr. Amanda Kahn, board-certified internist and longevity expert
- Dr. Luis-Emilio Garcia, VP of Global Medical Affairs and Cardiometabolic Health at Eli Lilly and Company
- Jason Brett, principal U.S. medical head at Novo Nordisk
Why the Buzz About GLP-1s?
“Over 110 million Americans have obesity, and by 2030, cardiometabolic diseases could affect a third of adults globally,” says Dr. Luis-Emilio Garcia. GLP-1 medications play a vital role in managing weight and metabolic health.
Dr. Amanda Kahn adds, “GLP-1s have transformed weight management and metabolic medicine by targeting biological causes of overeating and inflammation, beyond lifestyle changes.”
Key Differences Between Semaglutide and Tirzepatide
“Semaglutide and tirzepatide are powerful tools in metabolic medicine, working differently,” says Dr. Kahn. Semaglutide mimics the body’s GLP-1 hormone, while tirzepatide targets both GLP-1 and GIP receptors.
What is Wegovy?
Jason Brett explains, “Wegovy helps people with obesity reduce weight by mimicking the GLP-1 hormone, regulating appetite and promoting weight loss.”
- Reduce cardiovascular events
- Help adults and children lose weight
- Treat metabolic dysfunction-associated steatohepatitis
What is Zepbound?
Dr. Garcia states, “Zepbound is a dual receptor agonist, targeting GIP and GLP-1 receptors to reduce appetite and body weight, with extra benefits for fat metabolism and insulin sensitivity.”
Zepbound is FDA-approved for obesity and moderate-to-severe obstructive sleep apnea.
Side Effects of Wegovy and Zepbound
Both medications may cause gastrointestinal symptoms like nausea and bloating, but Zepbound may have milder initial side effects due to the GIP pathway addition.
“Side effects are usually mild to moderate and transient,” Brett explains. Dr. Kahn suggests starting low, staying hydrated, and working with an experienced provider for optimal tolerance.
Which is More Effective?
Dr. Kahn notes that tirzepatide typically results in more substantial weight loss compared to semaglutide. Clinical studies show patients using tirzepatide lose about 22-25% of their total body weight, while semaglutide users lose around 15%.
Dr. Kahn refers to the SURMOUNT-5 clinical trial (published in May 2025), which involved 751 adults with obesity or overweight but without type 2 diabetes. The study compared the effects of Wegovy and Zepbound on these individuals, with Zepbound resulting in greater weight reduction – 20.2 percent or 50.3 lbs compared to Wegovy’s 13.7 percent or 33.1 lbs.
Dr. Kahn explains that Tirzepatide’s dual mechanism, targeting GLP-1 and GIP receptors, creates a more balanced metabolic effect, enhancing fat burning while preserving lean muscle. Zepbound, with the addition of GIP, shows fewer gastrointestinal side-effects compared to semaglutide. As a first-line agent for a metabolic reset, Dr. Kahn usually prescribes Zepbound due to its broader metabolic and longevity benefits.
When it comes to choosing between Wegovy and Zepbound, Dr. Kahn considers individual tolerance, response, and health goals rather than a simple comparison of strength. If a patient is already progressing well on Wegovy, Dr. Kahn may not switch unless there is interest in trying a different approach or a plateau in progress.
In terms of who should and should not take GLP-1 medications, Dr. Kahn mentions that while these medications were initially developed for people with obesity or overweight with related health issues, other factors like body composition, visceral fat accumulation, insulin resistance, fatty liver, or inflammatory conditions are also considered. However, individuals with specific health conditions like medullary thyroid cancer, MEN2, severe gastrointestinal motility disorders, underweight individuals, or those with a history of disordered eating should not take these medications.
The goal of using GLP-1 medications is to restore balance and improve metabolic flexibility rather than solely focusing on weight loss or extreme measures. Personalization and tailoring treatment to the individual are key principles in longevity medicine.