Millions are turning to powerful new injectable medications like Ozempic, Wegovy, Mounjaro, and Zepbound (part of the GLP-1 class) in the hope of significant weight loss. While clinical trials have shown impressive results, new research from the Cleveland Clinic suggests that the picture in the “real world” of everyday patient care might look a bit different.
A study published in the Obesity Journal analyzed data from nearly 8,000 patients with severe obesity who were prescribed these injectable GLP-1 medications between 2021 and 2023. The core finding? Patients treated in real-world settings experienced significantly less weight loss compared to participants in controlled clinical trials.
Why the Difference? Discontinuation and Dosage Key Factors
The research pinpointed two major reasons for this gap between trial results and real-world outcomes:
- High Discontinuation Rates: The study found that a substantial number of patients stopped taking their medication. Over 20% discontinued within the first three months, and an additional 32% stopped between three and twelve months.
- Lower Dosages: More than 80% of participants in the real-world study were on lower maintenance dosages than those typically used in clinical trials to achieve maximum effect.
The amount of weight lost correlated directly with how long patients stayed on the treatment. After one year:
Those who discontinued early (within 3 months) lost only about 3.6% of their body weight on average.
Those who discontinued later (3-12 months) lost around 6.8%.
Patients who continued treatment beyond a year saw an average weight loss of approximately 12%.
This 12% figure for continuous users is notably lower than the 15% to 20% average weight loss reported in many clinical trials. However, the study revealed that patients who continued treatment AND were on higher, trial-like dosages achieved better results, with average weight loss reaching 13.7% for semaglutide users and an impressive 18% for tirzepatide users. This suggests the medications retain their potential effectiveness when taken consistently at adequate doses.
Reasons Behind Discontinuation
The study highlights several common barriers that prevent patients from staying on treatment:
High Out-of-Pocket Costs: The significant price of these medications remains a major hurdle.
Insurance Coverage Issues: Difficulty obtaining or maintaining insurance approval for coverage.
Side Effects: Managing common side effects like nausea, vomiting, and diarrhea can be challenging for some patients.
Supply Shortages: Ongoing issues with medication availability have forced many patients to interrupt or stop treatment.
Beyond Weight Loss: Impact on Blood Sugar
The study also examined the effect of these drugs on blood sugar levels in patients with pre-diabetes. Maintaining treatment was crucial for improving glycemic control. Nearly 68% of patients who continued therapy achieved normal blood sugar levels, compared to only about 30-40% of those who discontinued.
Another Real-World Comparison: Mounjaro vs. Ozempic
Adding another layer to the real-world picture, a separate study published in JAMA Internal Medicine directly compared Mounjaro (tirzepatide) and Ozempic (semaglutide) for weight loss in adults with overweight or obesity using real-world healthcare data.
This research found that Mounjaro was significantly more effective for weight loss. At one year, patients on tirzepatide lost over 15% of their body weight on average, while those on semaglutide lost approximately 8%. Mounjaro users were also more than twice as likely to achieve a weight loss of 10% or more.
Interestingly, this study also noted high discontinuation rates for both* medications (over 50% within one year), reinforcing that staying on treatment is a widespread challenge in real-world use, regardless of which specific GLP-1 drug is prescribed.
Implications for Patients and Providers
According to Dr. Hamlet Gasoyan, lead author of the Cleveland Clinic study, these findings provide valuable information for healthcare providers and patients. Understanding real-world usage patterns and outcomes is essential for setting realistic expectations and making informed decisions about the role of these medications in managing obesity.
The research underscores that while GLP-1 drugs are powerful tools for weight management and improving metabolic health, achieving the transformative results seen in clinical trials heavily depends on patients being able to continue treatment consistently and, often, at clinically effective dosages. Addressing the practical barriers of cost, access, side effects, and supply is critical to helping patients maximize the potential benefits of these therapies in their daily lives.
