A new study published in the journal Obesity reveals that GLP-1 receptor agonist medications—such as semaglutide (Wegovy) and tirzepatide (Zepbound)—produce smaller weight loss outcomes in real-world settings compared to the results seen in clinical trials.
Researchers from the Cleveland Clinic analyzed 7,881 adult patients with obesity who did not have type 2 diabetes, observed between 2021 and 2023. Their findings highlight a consistent trend: while these medications are clinically effective, results in daily life are less dramatic and discontinuation rates are higher.
Key Findings
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Discontinuation rates: Nearly 50% of real-world users stopped taking GLP-1 medications within the first year—much higher than the 14–17% seen in clinical trials.
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Average weight loss: Real-world users of semaglutide lost around 8% of body weight after one year, compared to 15% in trials. For tirzepatide, weight loss averaged 12% versus 20% at higher doses in clinical studies.
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Lower dosing: Many patients used smaller doses than those tested in trials, possibly explaining part of the gap in outcomes.
Possible Reasons for the Gap
Experts point to several real-world factors that limit results:
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Medication cost and insurance coverage
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Side effects such as nausea and fatigue
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Difficulty sustaining lifestyle changes like diet and exercise
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Limited access to high-dose prescriptions
Despite these challenges, the researchers observed that patients did not regain weight as quickly as trial participants once stopping the medication—suggesting that even partial adherence may offer benefits for long-term weight maintenance.
What It Means for Patients
GLP-1 medications remain a powerful option for people living with obesity, but they work best as part of a comprehensive lifestyle strategy. Sustainable weight management still depends on nutrition, physical activity, and behavioral support.
Healthcare professionals recommend combining medication with a structured diet plan, physical activity routine, and stress-management practices for the best outcomes.
The Takeaway
This study underscores an important truth: clinical trial conditions rarely reflect daily life. Real-world success depends on individualized care, accessible pricing, and consistent lifestyle support. As research continues, clinicians aim to better understand how behavioral and economic factors affect adherence—and how to design more sustainable obesity treatments.
