Real-world study finds less weight loss with GLP-1 drugs due to early discontinuation

Real-world study finds less weight loss with GLP-1 drugs due to early discontinuation

A Cleveland Clinic study shows that semaglutide and tirzepatide injectable GLP-1 anti-obesity drugs produce less weight loss in a real-world setting as patients discontinue treatment or use lower maintenance doses. Treatment decline also negatively affected glycemic control in patients with prediabetes. The study was published in theObesity Journal.

Our study shows that patients treated with semaglutide or tricepatide for obesity lost less weight on average in a regular clinical setting than in randomized clinical trials. According to our data, this could be explained by higher discontinuation and lower maintenance doses in clinical practice compared to randomized clinical trials. “

Hamlet Gasoyan, Ph.D., lead author of the study and researcher at Cleveland Clinic's Center for Value-Based Care Research

Semaglutide (sold under the brand names Wegovy and Ozempic) and tirzepatide (sold under the brand names Zepbound and Mounjaro) are FDA-approved medications for the treatment of type 2 diabetes and chronic weight management. While randomized clinical trials have demonstrated the effectiveness of these medications, Drs. Gasoyan and colleagues examined their effect on weight loss and blood sugar regulation (glycemic control) in a real-world setting.

This retrospective cohort study at the Cleveland Clinic included 7,881 adult patients with an average body mass index (BMI) over 39, considered clinically severe obesity. Among participants, 1,320 had pre-diabetes at the start of the study, defined by blood sugar levels between 5.7% and 6.4%. Patients with pre-diabetes are at higher risk of developing type 2 diabetes, which is one of the most common complications of obesity.

Study participants began treating obesity with injectable forms of semaglutide or tirzepatide between 2021 and 2023. Researchers grouped patients who stopped their obesity medications early (within 3 months) and those who stopped taking them early (within 3 to 12 months). The follow-up of the study ended in December 2024.

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

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

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

The researchers also identified which factors were associated with a higher likelihood of weight loss of 10% or more, providing clinically significant health benefits in this patient population. Patients were more likely to achieve 10% or more weight loss after one year of treatment if they:

• hat ihre Medikamente nicht eingestellt oder spät eingestellt (gegenüber früh)
• hatten eine hohe Wartungsdosis
• Tirzepatid erhalten (gegen Semaglutid)
• waren weiblich (gegen männlich).

In addition to the factors that impact a person's weight trajectory, researchers tracked glycemic control in patients who had pre-diabetes at the start of the study.

Among participants with pre-diabetes, 33% of those who canceled their treatment early had normal blood glucose levels (defined by Hba1c level of 5.6 or lower), compared to 41% who canceled their treatment late and 67.9% who did not stop treatment.

“In our study, the majority of patients experienced pre-diabetes as they continued their treatment,” said Dr. Gasoyan. "Type 2 diabetes is one of the most common complications of obesity. Therefore, prevention of diabetes is very important. This study shows that stopping treatment, especially early, negatively affects both weight and glycemic control."

The most common reasons for discontinuing treatment were medication costs and insurance coverage issues, side effects, and medication shortages. A follow-up study is in progress to quantify why patients stop taking their obesity medications in a real-world setting.

In addition, researchers observed that patients who stopped obesity medications lost significantly less weight compared to those who continued, but their weight trajectories remained relatively stable. This will be further investigated to determine what additional weight management methods patients use after discontinuing obesity medications in real world settings.

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