Novo Nordisk recently announced compelling results from its STEP UP trial, indicating that a higher dose of semaglutide leads to significant weight loss in individuals with obesity. The trial involved over 1,400 participants, some of whom received a 7.2 milligram dose of semaglutide, achieving an average weight loss of approximately 20% over 72 weeks. This surpasses the typical weight loss observed with the currently available semaglutide-based drugs, Ozempic and Wegovy.
Semaglutide: A New Era in Obesity Treatment
Semaglutide, a GLP-1 receptor agonist, mimics the hormone GLP-1, which plays a crucial role in regulating appetite and metabolism. It is the active ingredient in Ozempic, a type 2 diabetes medication, and Wegovy, a higher-dose obesity drug. Wegovy received FDA approval in 2021, and since then, Ozempic has also been prescribed off-label for weight loss. In large-scale trials, Wegovy has demonstrated an average weight loss of around 15%, significantly exceeding the results typically achieved through diet, exercise, or older obesity medications.
The STEP UP Trial: Exploring Higher Doses
The STEP UP trial comprised three groups: a placebo group, a 2.4 milligram semaglutide group (equivalent to the Wegovy dose), and a 7.2 milligram semaglutide group. Participants who adhered to the weekly injection schedule in the 7.2 milligram group experienced an average weight loss of 20.7% after 72 weeks. This compares to 17.5% weight loss in the 2.4 milligram group and 2.4% in the placebo group. Even when considering participants who didn’t fully adhere to the schedule, the higher dose still outperformed the standard dose, with 18.7% weight loss compared to 15.6%.
Safety and Tolerability of Higher Dose Semaglutide
According to Novo Nordisk, the higher dose of semaglutide demonstrated a generally safe and tolerable profile in the trial. Side effects experienced by the 7.2 milligram group were comparable to those in the lower dose group. While GLP-1 receptor agonists are known to cause gastrointestinal side effects such as diarrhea or vomiting, these are typically mild to moderate and tend to diminish over time. Rarely, more severe complications like gastroparesis have been linked to GLP-1 drugs.
The Future of Semaglutide and the Obesity Treatment Landscape
Novo Nordisk anticipates that semaglutide will remain a leading treatment for obesity and diabetes, even with emerging competition from other pharmaceutical companies. The company will soon release results from its STEP UP T2D trial, which evaluated the 7.2 milligram dose in individuals with obesity and type 2 diabetes. However, even the highest dose of semaglutide is expected to face challenges.
Competition and Cost Considerations
Eli Lilly’s tirzepatide, the active ingredient in Mounjaro and Zepbound, outperformed Wegovy in a head-to-head trial, demonstrating an average weight loss of 20.2% compared to 13.7%. Other promising obesity drugs are also in development, potentially surpassing both tirzepatide and semaglutide. Cost remains a significant concern. The high list prices of current semaglutide formulations (around $1,000 per month) have drawn criticism, and the federal government has announced plans to negotiate Medicare prices for Ozempic and Wegovy, though any potential price reductions wouldn’t take effect until 2027. A higher dose of semaglutide, while potentially more effective, could come with a similar or even higher price tag.
Conclusion: A Promising but Potentially Pricey Future
While the future of obesity treatment holds significant promise, the cost of these medications remains a critical factor. The higher dose of semaglutide demonstrates encouraging weight loss results, but its potential price, along with competition from other emerging drugs, will shape its role in the evolving landscape of obesity management.
