Injectable medications for obesity found to produce smaller weight loss in a real-world setting

A Cleveland Clinic study shows that semaglutide and tirzepatide—injectable GLP-1 drugs for obesity—produce smaller weight loss in a real-world setting because patients discontinue treatment or use lower maintenance dosages. Treatment discontinuation also negatively impacted blood sugar control in patients with prediabetes. The study was published in the Obesity Journal.

Hamlet Gasoyan, Ph.D., lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said, “Our study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight on average in a regular clinical setting compared to what is observed in randomized clinical trials.

“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.”

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 shown the efficacy of those medications, Dr. Gasoyan and colleagues studied their effect on weight reduction and blood sugar regulation (glycemic control) in a real-world setting.

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

The study participants began treatment for obesity with injectable forms of semaglutide or tirzepatide between 2021 and 2023. Researchers grouped patients who discontinued their obesity medications into those who discontinued early (within three months) and late (within three to 12 months). The study’s follow-up ended in December 2024.

Researchers found that more than 20% of patients discontinued their medications early and 32% discontinued their medications late. In addition, more than 80% of study participants were on lower maintenance dosages of those medications (i.e., equal to or less than 1 mg for semaglutide and equal to or less than 7.5 mg for tirzepatide). The maintenance dose refers to the amount of medication needed to sustain a therapeutic effect.

One year after the start of the treatment, researchers found that the average weight reduction was 3.6% among the participants who discontinued their treatment early, compared to 6.8% for those who discontinued their treatment late. Those who did not discontinue treatment lost on average 11.9% body weight.

Those who did not discontinue treatment and were on high maintenance dosage of the medications lost 13.7% of their body weight with semaglutide and 18.0% with tirzepatide.

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

Researchers also identified what factors were associated with higher odds of achieving weight loss of 10% or more, which provides clinically significant health benefits in this patient population. Patients had higher odds of achieving 10% or greater weight reduction after one year of treatment if they:

• did not discontinue their medications or discontinued late (vs. early)
• were on high maintenance dosage
• received tirzepatide (vs. semaglutide)
• were female (vs. male).

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

Among the participants with pre-diabetes, 33% of those who discontinued their treatment early experienced normal blood sugar levels (defined by an HbA1c level of 5.6 or lower), compared to 41% who discontinued their treatment late, and 67.9% who did not discontinue treatment.

“In our study, the majority of the patients with pre-diabetes experienced normal blood sugar levels when they continued their treatment,” said Dr. Gasoyan. “Type 2 diabetes is one of the most common complications of obesity, so diabetes prevention is very important. This study highlights that treatment discontinuation, especially early, negatively affects both weight and glycemic control outcomes.”

The most common reasons for discontinuation of treatment included the cost of the medications and insurance coverage–related issues, side effects, and medication shortages. A follow-up study is in the works to quantify why patients discontinue their obesity medications in a real-world setting.

In addition, researchers observed that while patients who discontinued obesity medications lost significantly less weight compared to those who persisted, their weight trajectories remained relatively stable.

This will be studied further to identify what additional weight management methods patients are using in real world settings after discontinuation of obesity medications.

A Cleveland Clinic study shows that semaglutide and tirzepatide—injectable GLP-1 drugs for obesity—produce smaller weight loss in a real-world setting because patients discontinue treatment or use lower maintenance dosages. Treatment discontinuation also negatively impacted blood sugar control in patients with prediabetes. The study was published in the Obesity Journal.

Hamlet Gasoyan, Ph.D., lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said, “Our study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight on average in a regular clinical setting compared to what is observed in randomized clinical trials.

“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.”

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 shown the efficacy of those medications, Dr. Gasoyan and colleagues studied their effect on weight reduction and blood sugar regulation (glycemic control) in a real-world setting.

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

The study participants began treatment for obesity with injectable forms of semaglutide or tirzepatide between 2021 and 2023. Researchers grouped patients who discontinued their obesity medications into those who discontinued early (within three months) and late (within three to 12 months). The study’s follow-up ended in December 2024.

Researchers found that more than 20% of patients discontinued their medications early and 32% discontinued their medications late. In addition, more than 80% of study participants were on lower maintenance dosages of those medications (i.e., equal to or less than 1 mg for semaglutide and equal to or less than 7.5 mg for tirzepatide). The maintenance dose refers to the amount of medication needed to sustain a therapeutic effect.

One year after the start of the treatment, researchers found that the average weight reduction was 3.6% among the participants who discontinued their treatment early, compared to 6.8% for those who discontinued their treatment late. Those who did not discontinue treatment lost on average 11.9% body weight.

Those who did not discontinue treatment and were on high maintenance dosage of the medications lost 13.7% of their body weight with semaglutide and 18.0% with tirzepatide.

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

Researchers also identified what factors were associated with higher odds of achieving weight loss of 10% or more, which provides clinically significant health benefits in this patient population. Patients had higher odds of achieving 10% or greater weight reduction after one year of treatment if they:

• did not discontinue their medications or discontinued late (vs. early)
• were on high maintenance dosage
• received tirzepatide (vs. semaglutide)
• were female (vs. male).

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

Among the participants with pre-diabetes, 33% of those who discontinued their treatment early experienced normal blood sugar levels (defined by an HbA1c level of 5.6 or lower), compared to 41% who discontinued their treatment late, and 67.9% who did not discontinue treatment.

“In our study, the majority of the patients with pre-diabetes experienced normal blood sugar levels when they continued their treatment,” said Dr. Gasoyan. “Type 2 diabetes is one of the most common complications of obesity, so diabetes prevention is very important. This study highlights that treatment discontinuation, especially early, negatively affects both weight and glycemic control outcomes.”

The most common reasons for discontinuation of treatment included the cost of the medications and insurance coverage–related issues, side effects, and medication shortages. A follow-up study is in the works to quantify why patients discontinue their obesity medications in a real-world setting.

In addition, researchers observed that while patients who discontinued obesity medications lost significantly less weight compared to those who persisted, their weight trajectories remained relatively stable.

This will be studied further to identify what additional weight management methods patients are using in real world settings after discontinuation of obesity medications.