Weight loss from GLP-1 drugs is not as robust in real-world settings

There is high demand for drugs for diabetes and obesity, known as glucagon-like peptide-1, or GLP-1, agonists. When combined with an appropriate diet and exercise program, GLP-1 can provide substantial health benefits for patients. Before several GLP-1s became popular treatments for obesity, this class of drugs had been used for many years in the treatment of type 2 diabetes. And a GLP-1 called Wegovy (semaglutide) received approval this spring. additional cardiovascular indication from the Food and Drug Administration. Additional indications for GLP-1 could be considered in the area of ​​chronic kidney disease as well as non-alcoholic steatohepatitis, or NASH.

But so far, the real-world evidence for weight loss from GLP-1 use is not as strong as clinical trial data indicates. A study published last month in the Journal of the American Medical Association shows that although patients achieved a statistically significant degree of average weight loss of 3.7% one year after starting the medication, the extent The overall reported benefits were lower than those reported in the trials. The new study looks at real-world data from more than 3,000 patients to measure their weight loss over a one-year period of GLP1 use.

The authors write that “patients have high expectations of achieving substantial weight reductions from GLP-1 medications. Our clinical results suggest that this was not the case for most patients in our cohort; however, those who persisted with drug coverage experienced weight losses comparable to those demonstrated in corresponding clinical trials.

And in a paper published in 2023, researchers found that although significant weight loss was achievable with GLP-1 in type 2 diabetes patients, the average weight reduction was relatively modest, 2.2% after 72 weeks of treatment.

Additionally, in a pre-print publication this year, researchers analyzed the actual effectiveness of GLP-1 use compared to regular care management in a control group. They found that “treatment cohorts in randomized controlled clinical trials generally report more pronounced effects than control groups for the primary outcomes assessed.”

These studies demonstrate key differences between effectiveness in less controlled real-world environments and in clinical trials.

Further complicating matters is the issue of real-world patient persistence with respect to GLP-1. Discontinuation can reach 85% after two years of treatment, according to a study conducted by Prime Therapeutics, a pharmaceutical benefits manager.

Prime Therapeutics released an analysis in July that showed that only about 15% of people who started taking GLP-1 drugs for weight loss persisted after two years. And 47% of patients were still taking GLP-1 at 180 days; 29% at one year; and 15% at two years. The drugs included in the research were Victoza (liraglutide), Saxenda (liraglutide), Ozempic (semaglutide), and Wegovy (semaglutide).

A host of other recent publications also show relatively high percentages of patients dropping out as early as four weeks into treatment and that discontinuation increases over time, often before patients achieve a clinically significant level of weight loss. For example, 58% of patients stopped treatment before achieving a 5% weight reduction from baseline, according to findings published by the Blue Cross Blue Shield Association. Additionally, 30% of patients discontinued use within the first month.

Evidence that many people may stop taking obesity medications shortly after starting treatment casts doubt on the durability of weight loss to achieve positive long-term health outcomes. To benefit from the health benefits of GLP-1, it is essential that people prescribed GLP-1 continue to take it at least long enough to achieve clinical success, and preferably longer to avoid possible rebound. weight once they stop taking the medication.

In the real world, there are a range of factors that can contribute to nonpersistence, including drug supply shortages, adverse reactions, high out-of-pocket costs, and actual weight loss not meeting patient expectations. .