Cleveland Clinic research shows injectable obesity medications produce less weight loss in real-world settings than in randomised clinical trials

• Stopping treatment and low maintenance doses reduced the effectiveness of GLP-1 medications on body weight and blood sugar levels.

Cleveland. A Cleveland Clinic study shows that semaglutide and tirzepatide, injectable GLP-1 medications for obesity, produce less weight loss in real-world clinical settings because patients stop treatment or use lower maintenance doses. Stopping treatment also had a negative effect on blood sugar control in patients with prediabetes. The study was published in the journal Obesity.

Hamlet Gasoyan, Ph.D., lead author of the study and a researcher at Cleveland Clinic’s Center for Value-Based Care Research, said: “This study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight, on average, in a real-world clinical setting than was seen in randomised clinical trials. According to our data, this may be explained by the higher rates of treatment discontinuation and the lower maintenance doses used in clinical practice, compared with the controlled settings of the trials.”

Semaglutide (sold as Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro) are FDA-approved medications for treating type 2 diabetes and for chronic weight management. Although randomised clinical trials have shown their effectiveness, Dr. Gasoyan and his team studied their impact on weight loss and glycaemic control in a real-world setting.

This retrospective Cleveland Clinic cohort study included 7,881 adult patients with an average body mass index (BMI) above 39, which is classed as clinically severe obesity. Of the participants, 1,320 had prediabetes at the start of the study, defined as blood sugar levels between 5.7% and 6.4%. People with prediabetes are at greater risk of developing type 2 diabetes, one of the most common complications of obesity.

Participants began obesity treatment with injectable semaglutide or tirzepatide between 2021 and 2023. The researchers grouped patients who stopped their medication into early discontinuation (within the first 3 months) and late discontinuation (between 3 and 12 months). Study follow-up ended in December 2024.

The researchers found that more than 20% of patients stopped their medication early and 32% stopped late. In addition, more than 80% of study participants were on lower maintenance doses of these medications (that is, 1 mg or less of semaglutide and 7.5 mg or less of tirzepatide). The maintenance dose is the amount needed to sustain a therapeutic effect.

One year after starting treatment, the researchers found that average weight loss was 3.6% among those who stopped treatment early, compared with 6.8% among those who stopped late. Those who did not stop treatment lost an average of 11.9% of their body weight. Patients who did not stop and were also on high maintenance doses lost 13.7% of their weight with semaglutide and 18.0 % with tirzepatide.

“Our findings on real-world use patterns of these medications and their associated clinical outcomes can help healthcare professionals and their patients make informed decisions about the role of treatment continuity and maintenance dose in achieving clinically meaningful weight reduction,” said Dr. Gasoyan.

The researchers also identified the factors associated with a greater likelihood of achieving weight loss of 10% or more, which brings significant health benefits for this population. Patients were more likely to reach this goal after a year of treatment if they: did not stop treatment or stopped late (compared with early discontinuation); were on high maintenance doses; received tirzepatide (compared with semaglutide); and were women (compared with men).

As well as studying the factors affecting body weight trajectory, the researchers also monitored glycaemic control in patients with prediabetes at the start of the study.

Among participants with prediabetes, 33 % of those who stopped treatment early reached normal blood sugar levels (defined as an HbA1c of 5.6 or lower), compared with 41% of those who stopped late and 67.9% of those who did not stop treatment.

“In our study, most patients with prediabetes reached normal glucose levels when they continued their treatment,” said Dr. Gasoyan. “Type 2 diabetes is one of the most common complications of obesity, so prevention is very important. This study highlights that stopping treatment, especially early, has a negative effect on both weight and glycaemic control.”

The most common reasons for stopping treatment included the cost of the medications, insurance coverage issues, side effects and drug shortages. A follow-up study is already under way to quantify why patients stop their obesity treatments in clinical practice.

The researchers also observed that, although patients who stopped treatment lost significantly less weight than those who continued, their weight trajectories remained relatively stable. This will be studied further to identify what other weight management methods patients are using in real-world settings after stopping treatment.

About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical centre that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding care based on the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognised in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 82,600 employees worldwide are more than 5,786 salaried physicians and researchers, and 20,700 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,728-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals and 280 outpatient facilities, including locations in northeast Ohio; Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2024, there were 15.7 million outpatient encounters, 333,000 hospital admissions and observations, and 320,000 surgeries and procedures throughout Cleveland Clinic’s health system. Patients came for treatment from all 50 states and 112 countries.