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Key factors affecting long-term weight loss in patients prescribed GLP-1 AR medications

A Cleveland Clinic study identified key factors that may affect long-term weight loss in obese patients 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 loss varied significantly by the drug’s active agent, treatment indication, dose, and persistence in drug use,” said Hamlet Gasoyan, Ph.D., senior author of the study and an investigator at the Cleveland Clinic Value-Based Care Research Center.

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. These 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 are limited real-world data on factors associated with long-term weight change and clinically meaningful weight loss.

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

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 baseline, the mean baseline body mass index among study participants was 38.5; 82.2% had type 2 diabetes as an indication for treatment. Among patients, 68.5% were white, 20.3% were black, and 7.0% were Hispanic. More than half of participants were women (54.7%). The majority of patients were treated for type 2 diabetes. Overall, 39.6% were prescribed semaglutide for type 2 diabetes, 42.6% were prescribed liraglutide for type 2 diabetes, 11.1% were prescribed semaglutide for obesity, and 6.7% were prescribed liraglutide for obesity.

The results show that one year after filling the initial prescription, weight change was associated with the following factors:

  • Medication persistence. On average, patients who were persistent with their medication at 1 year experienced a weight change of -5.5% versus -2.8% among patients who had 90 to 275 days of medication coverage during the first year and -1.8% among those who had less than 90 days of coverage.

Researchers found that four in ten patients (40.7%) were still taking their medication one year after receiving their initial prescription. The proportion of patients still taking semaglutide was 45.8% compared with 35.6% of patients receiving liraglutide.

Among patients who persisted on their medication at 12 months, the average reduction in body weight was -12.9% with semaglutide for obesity, compared with -5.9% with semaglutide for type 2 diabetes. The reduction in body weight was -5.6% with liraglutide for obesity, compared with -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 a weight reduction of 10% or more.

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

Among patients who persisted with their medication one year after their initial prescriptions, the proportion achieving 10% or more weight loss 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.

According to multivariate analysis of the study that took into account relevant sociodemographic and clinical variables, the following factors were associated with increased odds of achieving 10% or more weight reduction one year after initial prescriptions:

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

In a previous study, Dr. Gasoyan and colleagues looked at factors that influence long-term use of anti-obesity medications. Future research will continue to explore the persistence and health outcomes of patients on anti-LP-1RA drugs.

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