Real-world evidence suggests that the weight loss achieved with glucagon-like peptide-1 (GLP-1) agonists may not be as robust as indicated by clinical trial data. A recent study published in the Journal of the American Medical Association (JAMA) revealed that patients experienced an average weight loss of only 3.7% one year after starting GLP-1 medications. This is a statistically significant result, but the overall magnitude of benefit was less than that reported in controlled trials.
Modest Weight Reduction in Real-World Settings
The JAMA study examined real-world data from over 3,000 patients and found that many had high expectations for substantial weight reduction with GLP-1 medications, expectations that were often unmet. The authors noted, "patients have high expectations to achieve substantial weight reductions with GLP-1 medications. Our clinical findings suggest that this was not the case for most patients in our cohort; however, those who persisted with the medication coverage experienced weight losses comparable with those shown in corresponding clinical trials."
Another study published in 2023 found that among type 2 diabetes patients, the average weight reduction with GLP-1s was a relatively modest 2.2% after 72 weeks of treatment. These findings highlight the differences between the controlled environments of clinical trials and the less controlled real-world settings.
High Discontinuation Rates
Patient persistence with GLP-1s is a significant challenge. A study by Prime Therapeutics, a pharmacy benefit manager, indicated that discontinuation rates can be as high as 85% by the end of two years of treatment. Their analysis showed that only about 15% of individuals who started taking GLP-1 drugs for weight loss persisted after two years. Specifically, 47% of patients were still taking a GLP-1 at 180 days, 29% at one year, and only 15% at two years. The drugs included in the research were Victoza (liraglutide), Saxenda (liraglutide), Ozempic (semaglutide) and Wegovy (semaglutide).
Further evidence from the Blue Cross Blue Shield Association revealed that 58% of patients stopped treatment before achieving a 5% reduction in weight from their baseline level, and 30% discontinued use within the first month. These high discontinuation rates raise concerns about the sustainability of weight loss and the attainment of long-term positive health outcomes.
Factors Affecting Persistence
Several factors contribute to non-persistence in real-world settings, including medication supply shortages, adverse effects, high out-of-pocket costs, and a discrepancy between real-world weight reduction and patient expectations. To realize the health benefits conferred by GLP-1s, it is critical that patients continue to take them long enough to achieve clinical success and, ideally, longer to avoid potential weight rebound after discontinuing the medications.
