Key factors that impact long-term weight loss in patients prescribed GLP-1 RA medications

“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:

• 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:

“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.