Popular weight loss drugs such as Wegovy and Zepbound have shown incredible success in clinical trials

Think GLP-1s Guarantee Major Weight Loss? Real-World Data Says Otherwise But in the real world, patients might not lose as much weight—here's why

Popular weight loss drugs such as Wegovy and Zepbound have shown incredible success in clinical trials

In the real world, people who stopped GLP-1s early or took lower doses lost less weight.
Tatsiana Volkava / Getty Images

A new study found that real-world users of GLP-1 drugs lost less weight than people in clinical trials.
Study authors say the difference in weight loss is likely explained by people stopping their medication too early and taking lower doses.
For long-term success on GLP-1s, experts recommend sticking to the treatment and adopting a healthy lifestyle.

Wegovy, Zepbound, and other glucagon-like peptide-1 (GLP-1) drugs saw incredible success in clinical trials for weight loss and have since become hugely popular across the U.S. But do the medications actually work as well in the real world?

Past clinical trials have shown that:

Semaglutide (Ozempic and Wegovy) could lead to a 14.9% reduction in body weight over 68 weeks.
Tirzepatide (Mounjaro and Zepbound) could lead to a 20.9% reduction in body weight over 72 weeks.

However, a new study published on June 10 in Obesity found that patients taking these drugs outside of a study setting didn’t see the same kinds of results.

“In the real world, we observed weight reduction or weight loss was lower than what we [have] seen in randomized control trials,” said study author Hamlet Gasoyan, PhD, MPH, assistant professor of medicine and researcher at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

“The way we can explain it based on our data: Half of the patients discontinued the treatment during the first year, and eight out of 10 were on lower dosages of the studied medications,” Gasoyan told Health.

The results aren’t necessarily surprising, experts said, and aren’t a cause for concern among GLP-1 users. Even smaller amounts of weight loss can lead to meaningful cardiovascular and metabolic health benefits.

What Did GLP-1 Weight Loss Look Like in the Real World?

For this study, Gasoyan and his team looked at data from nearly 7,900 GLP-1 users in Ohio and Florida who were overweight or obese, but did not have type 2 diabetes. About three quarters of the participants were female, white, and had private insurance. There were 6,109 people taking semaglutide and 1,772 taking tirzepatide.

After one year, the average weight reduction among the participants was:

7.7% for semaglutide
12.4% for tirzepatide

In contrast, people in clinical trials lost 14.9% and 20.9% of their body weight on semaglutide or tirzepatide, respectively.

Why Don’t Weight Loss Drugs Work As Well Outside of Clinical Trials?

Richard Siegel, MD, endocrinologist and co-director of the Diabetes and Lipid Center at Tufts Medical Center, told Health that the results are in line with previous findings in the weight management field, where the effects of drugs are much greater in trials than they are in the real world.

There are a few reasons why this is the case:

Participants in studies are often healthier, or vulnerable groups with existing conditions aren’t recruited for studies.
Trials are conducted in ideal medical settings.

This means that, in the real world, patients may experience more severe side effects, or struggle to access their medication. As a result, they may opt to take a lower dose of a drug or stop taking it altogether, missing out on the medication’s full benefits.

Stopping Medication Early

In the latest Obesity study, about 22% of the semaglutide patients and about 16% of the tirzepatide patients stopped taking their medication throughout the first year of the trial. Shortly after the one-year mark, another 31% of semaglutide users and 34% of tirzepatide users quit their medication, too.

That means fewer than half of the participants continued taking their GLP-1 drug over the entire study period.

People who stopped taking tirzepatide or semaglutide within the first three months lost just 3.6% of their body weight, while those who quit after three to 12 months lost 6.8% of their body weight.

But why did so many people end their treatment early? Gasoyan said he’s working on research right now, which found that cost, insurance-related factors, and side effects are likely the top culprits.

Also, “supply shortages during the study period may have contributed to increased discontinuation rates—nearly three times higher than in clinical trials,” Osama Hamdy, MD, PhD, medical director of the Obesity Clinic Program and Inpatient Diabetes Program at Harvard Medical School, told Health.

Differences in Dosages

Though higher dosages of semaglutide and tirzepatide are linked to more weight loss in trials, “a lot of people can’t get to that dose because of intolerance“ and side effects, Siegel explained.

In Gasoyan’s study, about 80% of study participants were on a “low maintenance dose,” which is defined as less than 1.7 milligrams (mg) of semaglutide or less than 10 mg of tirzepatide. In clinical trials, participants took 2.4 mg of semaglutide and 15 mg of tirzepatide.

However, study participants who did take higher doses (like those in the clinical trials) did see comparable weight loss results: 13.7% with semaglutide and 18% with tirzepatide, just slightly below clinical trial results.

Higher doses were also linked to other health benefits, the study found.

“We had a subset of patients who had prediabetes in our study cohort,” Gasoyan explained. “Those who never discontinued the treatment had the higher chances of bringing back the glucose levels to the normal levels.”

What You Need to Know

Though you may not lose as much weight on semaglutide or tirzepatide compared to patients in clinical trials, even small amounts of weight loss can still be significant.

“We focus too much on how much more we can lose,” Amy Rothberg, MD, director of the Weight Management Program at the University of Michigan, told Health. “People can resolve a lot of their health conditions, as we know from the diabetes prevention program, with as little as 5% [body weight reduction].”

But if you’re looking for the best results possible, there are things you can do to increase your chances of seeing greater weight loss and metabolic benefits.

“The key is to go up on the dose, as long as side effects are not too limiting and weight loss isn’t too fast,” Babak Orandi, MD, PhD, obesity medicine specialist with the NYU Langone Health Weight Management Program, told Health.

In fact, in the new Obesity study, researchers found patients were much more likely to lose at least 10% of their body weight if they took a higher drug dose and didn’t end their medication early.

Healthy nutrition and exercise are also crucial if you want to optimize the effects of GLP-1 medications and lower the risk of side effects, experts agreed.

“People should eat slowly, eat less than they normally do, and avoid greasy or fatty foods when they start these medications or go up on the dosage,” Orandi said.

In the end, GLP-1 drugs work best when patients have a multidisciplinary team working to help them, Gasoyan, Siegel, and Rothberg emphasized.

Administrators can help ensure proper access for the medication through insurance pre-authorizations, while nutritionists and other lifestyle experts help you make necessary dietary and behavioral changes.

People who stop GLP-1 drugs are at risk of gaining weight again, so it’s these lifestyle changes that are really key for long-lasting results. “Without having changed their behaviors, they are set up for regaining the weight,” Rothberg said.

Edited by Health, where she edits and publishes news articles on trending health and wellness topics. Her work has been featured in The Heights, an independent student newspaper at Boston College, and Minnesota Monthly." tabindex="0" data-inline-tooltip="true"> Julia Landwehr

Julia Landwehr Julia is the associate news editor for Health, where she edits and publishes news articles on trending health and wellness topics. Her work has been featured in The Heights, an independent student newspaper at Boston College, and Minnesota Monthly. learn more Read more: