A recent study from the Cleveland Clinic has identified key factors influencing long-term weight loss in patients with obesity who were prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide and liraglutide. The retrospective cohort study, published in JAMA Network Open, analyzed data from 3,389 adult patients and revealed that the medication's active agent, dosage, treatment indication, and patient persistence significantly impact weight reduction outcomes.
Key Factors Influencing Weight Loss
The study, led by Hamlet Gasoyan, Ph.D., a researcher at Cleveland Clinic’s Center for Value-Based Care Research, examined the real-world effectiveness of these medications, which are FDA-approved for lowering blood sugar levels and promoting weight loss. The research team found that patients on semaglutide experienced a greater average weight reduction (-5.1%) compared to those on liraglutide (-2.2%). Furthermore, higher doses of either drug correlated with more substantial weight loss.
Persistence with the medication emerged as a critical factor. Patients who remained on treatment for a full year demonstrated better outcomes than those with shorter treatment durations. Specifically, 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.
Achieving Clinically Significant Weight Loss
The researchers also assessed the proportion of patients achieving a 10% or greater reduction in body weight, a threshold known to provide clinically significant health benefits. Overall, 37.4% of patients receiving semaglutide for obesity achieved this milestone, 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.
Multivariable Analysis Findings
A multivariable analysis, accounting for socio-demographic and clinical variables, identified several factors associated with higher odds of achieving 10% or more weight reduction. These included receiving semaglutide versus liraglutide, a high maintenance dose of the medication, obesity as the treatment indication versus type 2 diabetes, persistence with the medication, higher initial body mass index (BMI), and being female.
Implications for Clinical Practice
"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. He emphasized that real-world data can help manage expectations regarding weight reduction with GLP-1 RA medications and reinforce that persistence is key to achieving meaningful results.
The study underscores the importance of tailoring treatment strategies based on individual patient characteristics and treatment goals to optimize weight loss outcomes with GLP-1 RA medications.
