High-Dose Semaglutide Leads to Greater Weight Loss in Large Trial

The race to develop even more effective obesity drugs is heating up. Novo Nordisk this week announced People who took the mega-dose version of semaglutide lost significantly more body weight than normal in a large-scale trial.

Novo Nordisk’s STEP UP trial involved more than 1,400 people with obesity, some of whom were randomized to receive a 7.2-milligram dose of semaglutide. People who stayed on this dose lost about 20% of their initial weight over 72 weeks. The findings exceed the typical weight loss results seen with the existing semaglutide-based drugs Ozempic and Wegovy.

Semaglutide mimics the hormone GLP-1, which helps regulate our hunger and metabolism. It is the active ingredient in the type 2 diabetes drug Ozempic and higher doses of the anti-obesity drug Wegovy. Since Wegovy’s FDA approval in 2021, Ozempic is often prescribed off-label for weight loss. In Wegovy’s large-scale, placebo-controlled trials, people lost about 15% of their weight, far greater than the average weight loss seen with diet and exercise or older obesity drugs.

The advent of semaglutide opened a new era of obesity treatment. Both Novo Nordisk and its competitors have made efforts to develop the next generation of these drugs. Although Wegovy is now a higher-dose formulation of semaglutide (its maximum prescribed dose is 2.4 milligrams, compared to the maximum dose of one milligram for Ozempic), the company notes that the drug’s effectiveness has not yet reached its maximum.

The STEP UP trial included three groups: people who were given either a placebo, a Wegovy-sized dose of semaglutide of 2.4 milligrams, or a dose of 7.2 milligrams.

Looking at people who fully followed the drug schedule (weekly subcutaneous injection), those on the 7.2-milligram dose lost an average of 20.7% body weight after 72 weeks, compared to 17.5% for the 2.4-milligram group. and lost 2.4% body weight for the placebo group. Even when non-adherents were included, the higher-dose version still outperformed the original (18.7% lost body weight, 15.6%).

Most importantly, the higher-dose version of semaglutide was generally safe and well tolerated. In the trial, the 7.2-milligram group experienced comparable side effects to the low-dose group, according to Novo Nordisk. GLP-1 drugs are known to cause gastrointestinal symptoms such as diarrhea or vomiting, although these effects are often mild or moderate and disappear over time. Very rarely, scientists associate GLP-1 drugs with severe complications gastroparesis (gastric paralysis).

“The results from STEP UP further strengthen the clinical profile of semaglutide for the treatment of obesity, in addition to the health benefits already established with Wegovy,” said Martin Holst Lange, Executive Vice President of Development at Novo Nordisk. statement from the company.

The company will also soon release results from its STEP UP T2D trial, which tested the 7.2-milligram dose in people with obesity and type 2 diabetes. Assuming things go according to plan, semaglutide could have a long shelf life as a high-end obesity and diabetes treatment for Novo Nordisk, even as other companies are rapidly approaching with their own drug candidates on the way. But even its highest-dose version is expected to face stiff competition.

In a head-to-head test announced Late last year, Eli Lilly’s existing drug tirzepatide (the active ingredient in diabetes drug Mounjaro and obesity treatment Zepbound) outperformed Wegovy, losing an average of 20.2% body weight to 13.7%. Other obesity drugs in development has shown early but promising results that may overshadow both tirzepatide and semaglutide.

Another issue is cost. Current low-dose formulations of semaglutide have been available for years at this point, and their high list prices (about $1,000 per month) have angered both. public and legislators. Just this week, the federal government announced it will say it will schedule both Ozempic and Wegovy for the next round of its recently debuted drug negotiation program under Medicare (but any potential cuts won’t take effect until 2027). While a higher dose of semaglutide may be more effective in treating obesity, it would likely allow the company to continue to sell its drug at similar or higher prices than today’s versions.

The future of obesity treatment looks bright, but it will also come at a cost.