Popular Weight Loss Drugs Work Half as Well in Real Life

A new study of nearly 8,000 patients reveals that blockbuster weight loss medications like Ozempic and Wegovy produce significantly less weight loss in real-world clinical practice than in the clinical trials that made them famous.

The average patient lost just 8.7% of their body weight after a year, far below the 15-21% weight loss reported in clinical trials. The difference comes down to two major factors: patients frequently stop taking the medications, and doctors prescribe lower doses than used in research studies.

The findings, published in the journal Obesity, challenge the sky-high expectations surrounding GLP-1 medications that have transformed obesity treatment and captured public attention. While these drugs remain powerful tools for weight management, the research suggests their real-world impact may be more modest than many patients and doctors expect.

The Reality Gap

Researchers at Cleveland Clinic analyzed prescription records and health data from 7,881 patients who started taking semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound) for weight loss between 2021 and 2023. The results paint a sobering picture of how these medications perform outside carefully controlled research environments.

More than half of patients either stopped taking their medication within a year or never reached the higher doses that proved most effective in clinical trials. Specifically, 20% quit within three months, another 32% stopped between three and twelve months, and over 80% remained on lower maintenance doses throughout their treatment.

“Our study shows that patients treated for obesity with semaglutide or trizepatide lost less weight on average in a regular clinical setting compared to what is observed in randomized clinical trials,” said lead author Dr. Hamlet Gasoyan of Cleveland Clinic’s Center for Value-Based Care Research. “According to our data, this could be explained by higher rates of discontinuation and lower maintenance dosages used in clinical practice, compared to randomized clinical trial settings.”

Key Real-World Results:

• Average weight loss: 8.7% (compared to 15-21% in clinical trials)
• Early quitters (within 3 months): Lost only 3.6% of body weight
• Late quitters (3-12 months): Lost 6.8% of body weight
• Continuous users: Lost 11.9% of body weight
• High-dose continuous users: Lost up to 18% with tirzepatide

Why Patients Stop Taking These Drugs

The research identifies several barriers that prevent patients from achieving the dramatic weight loss seen in clinical trials. Cost tops the list, with many patients facing insurance coverage issues or prohibitive out-of-pocket expenses that can reach $1,000 or more per month.

Side effects also drive discontinuation, though the study didn’t quantify their specific impact. Common complaints include nausea, vomiting, and gastrointestinal problems that can make daily life uncomfortable. Additionally, medication shortages during the study period forced some patients to interrupt their treatment.

What’s particularly striking is that discontinuation rates in this real-world study far exceeded those seen in clinical trials. While research studies reported discontinuation rates of 14-17%, this analysis found over 52% of patients stopped treatment within the first year.

The Dose Makes the Difference

Perhaps more surprising than discontinuation rates was the widespread use of lower medication doses in clinical practice. The study revealed that 81% of patients taking semaglutide and 79% taking tirzepatide remained on lower maintenance doses—significantly below the levels that produced dramatic results in clinical trials.

This finding wasn’t highlighted in initial coverage but represents a crucial insight into why real-world results lag behind trial outcomes. Patients who did reach higher doses and stayed on treatment achieved weight loss much closer to clinical trial results: 13.7% with high-dose semaglutide and 18% with high-dose tirzepatide.

The reasons for lower dosing patterns aren’t entirely clear from the study, but may reflect doctors’ caution about side effects, insurance coverage limitations for higher doses, or patient tolerance issues.

Beyond Weight Loss: Blood Sugar Benefits

The study also tracked blood sugar control in 1,320 patients who had prediabetes when they started treatment. Here, the medication’s effectiveness clearly correlated with treatment persistence.

Among patients with prediabetes, 68% of those who continued treatment achieved normal blood sugar levels within a year, compared to just 33% of those who stopped early. This difference has important implications since people with obesity face elevated risks of developing Type 2 diabetes.

“Type 2 diabetes is one of the most common complications of obesity, so diabetes prevention is very important,” Gasoyan noted. “This study highlights that treatment discontinuation, especially early, negatively affects both weight and glycemic control outcomes.”

Who Benefits Most?

The research identified several factors that increased patients’ odds of achieving clinically significant weight loss of 10% or more. Women were nearly twice as likely as men to reach this threshold. Patients taking tirzepatide achieved better results than those on semaglutide, and those who reached higher maintenance doses saw substantially better outcomes.

Surprisingly, the study found that patients who stopped taking the medications didn’t regain weight as rapidly as expected based on clinical trial data. Weight trajectories remained relatively stable after discontinuation, suggesting patients may pursue other weight management strategies once they stop the medications.

What This Means for Patients

For the millions of Americans considering or currently taking these medications, the findings offer both caution and hope. While real-world results may not match the dramatic weight loss showcased in clinical trials, the medications still provide meaningful benefits for many patients—particularly those who can afford to stay on treatment long-term.

“Our findings about the real-world use patterns of these medications and associated clinical outcomes could inform the decisions of healthcare providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight reductions,” Gasoyan explained.

The research underscores the importance of addressing cost and access barriers that prevent patients from achieving optimal outcomes. As these medications become more widely available and potentially more affordable, their real-world effectiveness may improve significantly.

For now, patients and doctors should enter treatment with realistic expectations while working to maximize the chances of success through adequate dosing, sustained treatment, and comprehensive support for lifestyle changes. The drugs clearly work—just not quite as dramatically as the headlines might suggest.