Cleveland Clinic Study Identifies Key Factors That Can Impact Long-Term Weight Loss in Patients with Obesity Who Were Prescribed GLP-1 RA Medications

A Cleveland Clinic study identified key factors that can impact the long-term weight loss of patients with obesity who were prescribed injectable semaglutide or liraglutide for the treatment of type 2 diabetes or obesity. The study was published in JAMA Network Open.

“In patients with obesity who were prescribed semaglutide or liraglutide, we found that long-term weight reduction varied significantly based on the medication’s active agent, treatment indication, dosage and persistence with the medication,” said Hamlet Gasoyan, Ph.D., lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research.

Semaglutide (sold under the brand names Wegovy and Ozempic) and liraglutide (sold under the brand names Saxenda and Victoza) are glucagon-like peptide-1 receptor agonists, or GLP-1 RA medications. Those FDA-approved medications help lower blood sugar levels and promote weight loss.

Obesity is a complex chronic disease that affects more than 41% of the U.S. adult population. Clinical trials have shown that anti-obesity medications are effective; however, there is limited data in real-world settings regarding the factors associated with long-term weight change and clinically significant weight loss.

In this study, the researchers identified key factors that were associated with long-term weight loss of patients with obesity. They also indicated the elements that were linked to the probability of achieving 10% or more weight loss.

This retrospective cohort study included 3,389 adult patients with obesity who initiated treatment with injectable semaglutide or liraglutide between July 1, 2015, and June 30, 2022. Follow-up ended in July 2023.

At the start of the study, the median baseline body mass index among study participants was 38.5; 82.2% had type 2 diabetes as treatment indication. Among the patients, 68.5% were white, 20.3% were Black, and 7.0% were Hispanic. More than half of the participants were female (54.7%). Most of the patients received treatment for type 2 diabetes. Overall, 39.6% were prescribed semaglutide for type 2 diabetes, 42.6% liraglutide for type 2 diabetes, 11.1% semaglutide for obesity, and 6.7% liraglutide for obesity.

Results show that one year after the initial prescription’s fill, weight change was associated with the following factors:

1. The medication’s active agent. On average, weight change was -5.1% with semaglutide versus -2.2% with liraglutide.
2. The dosage. Patients experienced -3.5% mean weight change with low maintenance dose versus -6.6% with high dose.
3. Treatment indication. Patients who received the medications for type 2 diabetes experienced -3.2% in mean weight change compared to -5.9% for obesity treatment.
4. Persistence with medication. On average, patients who were persistent with the medication at one year experienced -5.5% weight change versus -2.8% among patients who had 90-275 medication coverage days within the first year and -1.8% among those with less than 90 covered days.

Researchers found that four in 10 patients (40.7%) were persistent with their medication one year after their initial prescription’s fill. The proportion of patients who were persistent with semaglutide was 45.8% versus 35.6% in patients receiving liraglutide.

Among patients who persisted with their medication at 12 months, the average reduction in body weight was -12.9% with semaglutide for obesity, compared to -5.9% with semaglutide for type 2 diabetes. The reduction in body weight was -5.6% with liraglutide for obesity, compared to -3.1% with liraglutide for type 2 diabetes.

Studies have shown that achieving sustained weight loss of 10% or more provides clinically significant health benefits. With that in mind, Dr. Gasoyan and colleagues looked at the proportion of patients who achieved 10% or more weight reduction.

Overall, 37.4% of patients receiving semaglutide for obesity achieved 10% or more body weight reduction compared to 16.6% of patients receiving semaglutide for type 2 diabetes. In comparison, 14.5% of those receiving liraglutide for obesity achieved 10% or more body weight reduction versus 9.3% of those receiving liraglutide for type 2 diabetes.

Among patients who persisted with their medication one year after their initial prescriptions, the proportion who achieved 10% or more weight reduction was 61% with semaglutide for obesity, 23.1% with semaglutide for type 2 diabetes, 28.6% with liraglutide for obesity, and 12.3% with liraglutide for type 2 diabetes.

Based on the study’s multivariable analysis that accounted for relevant socio-demographic and clinical variables, the following factors were associated with higher odds of achieving 10% or more weight reduction one year after the initial prescriptions:

• Patients who received semaglutide versus liraglutide
• A high maintenance dose of the medication versus low
• Obesity as a treatment indication versus type 2 diabetes
• Patients who persisted with the medication within the first year or had between 90-275 days of medication coverage versus less than 90 days of medication coverage
• Patients who had higher initial BMI
• Patients who were female versus male

“Our findings could help inform patients and providers regarding some of the key factors that are associated with the probability of achieving sustained weight loss of a magnitude large enough to provide clinically significant health benefits,” said Dr. Gasoyan. “Having real-world data could help manage expectations regarding weight reduction with GLP-1 RA medications and reinforce that persistence is key to achieve meaningful results.”

In a previous study, Dr. Gasoyan and colleagues looked at the factors influencing the long-term use of anti-obesity medications. Future research will continue to explore patients’ persistence and health outcomes with GLP-1 RA medications.

Dr. Gasoyan is supported by a grant from the National Cancer Institute.