GLP-1 anti-obesity drugs lead to substantial weight loss in the “real world”

March 25, 2024

We know that the GLP-1 anti-obesity drugs lead to substantial weight loss in clinical trials; semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) are associated with about 15% or more weight loss in structured clinical trials. But prescription drugs often don’t work as well in the “real world’ outside of clinical trials. Epic Research, which uses claims from the Epic electronic medical record’s data warehouse, which has over 200 million patient records, has published research demonstrating that the GLP-1 medications lead to sustained weight loss outside of clinical trials.

The study of over 410,000 who were on GLP-1 medications for any reason showed that treatment with maximum doses of tirzepatide was associated with 15% weight loss, and injectable semaglutide was associated with 10% weight loss. Oral semaglutide (Rybelsus) and injectable liraglutide (Saxenda/Victoza) and dulaglutide (Trulicity, not marketed for obesity treatment), were associated with <4% weight loss at maximal doses. Given when these medications were approved, the sample had a high proportion of diabetics.

This month, sales of Zepbound were higher than sales of Wegovy for the first time, even though Zepbound is still not on the formulary for at least one large pharmacy benefit manager. This is not a surprise, given Zepbound’s increased impact and (slightly) lower cost. However, the weight loss possible with Wegovy will also lead to substantial improvement of overall health and decrease in health risks for most obese people. Wegovy has been approved by the FDA to reduce risk of major adverse cardiovascular events (MACE) in those with a history of MACE, but studies of Zepbound are still pending. I expect that these will also show lower risk of MACE, although we won’t know until the studies are finished and published.

Five percent weight loss would be considered a good response to a dietary intervention, and most who lose weight with diets regain a substantial portion of that weight subsequently. 

Implications for employers:

-        This demonstrates that two of the GLP-1 drugs (tirzepatide and semaglutide, both injectable) are associated with much more weight loss than even especially effective diets.

-        Oral semaglutide (only FDA approved for diabetes treatment) and injectable liraglutide, (FDA approved for obesity treatment as Saxenda,) lead to relatively modest amount of weight loss. These less-effective treatments are just as expensive as tirzepatide and injectable semaglutide.

-        Liraglutide is likely to be the first GLP-1 to become available as a generic in two years; this data suggests that its clinical value is substantially lower than the other two drugs, even if its price goes down.

-        Some formularies might include only one of the two highly potent GLP-1 medications, which is reasonable as both offer substantial benefit.

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Tomorrow: March is Colorectal Cancer Screening Awareness Month