A higher dose of semaglutide results in greater weight loss in larger trials

The race is on to develop more effective obesity drugs. Novo Nordisk this week Announce People who took its mega-dose version of semaglutide lost significantly more weight than usual in a large-scale trial.

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

Semaglutide mimics the hormone GLP-1, which helps regulate hunger and our metabolism. It is the active ingredient in the type 2 diabetes drug Ozempic and the high-dose obesity drug Wegovy. Since the FDA approval of Wegovy 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, which is much higher than the average weight loss seen with diet and exercise or with older obesity drugs.

The advent of semaglutide has ushered in a new era in obesity treatment. Novo Nordisk and its competitors have made efforts to develop the next generation of these drugs. While Wegovy is a higher-dose formulation of semaglutide (the maximum prescribed dose is 2.4 milligrams, compared to the maximum dose of 1 milligram for Ozempic), the company stresses that the drug’s effectiveness has not yet reached its maximum.

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

When looking at people who adhered exactly to the medication schedule (a weekly subcutaneous injection), those taking the 7.2 milligram dose lost an average of 20.7% of body weight after 72 weeks, compared to 17.5% of body weight lost for the 2.4 milligram group. And 2.4% lost body weight compared to the placebo group. Even when including people who were not fully adherent, the higher-dose version still outperformed the original version (18.7% of body weight lost compared to 15.6%).

Equally important, the higher-dose version of semaglutide appears to be generally safe and tolerable. In the trial, the group taking 7.2 milligrams experienced side effects that were similar to the lower 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 to moderate and tend to fade over time. In rare cases, scientists have linked GLP-1 drugs to severe complications such as: Gastroparesis (stomach paralysis).

“The STEP UP results further strengthen the clinical profile of semaglutide for the treatment of obesity, in addition to the health benefits already identified 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 the STEP UP T2D trial, which tested the 7.2 milligram dose for people with obesity and type 2 diabetes. Assuming things go as planned, semaglutide will likely have an extended shelf life as a first-line treatment for obesity and diabetes for Novo Nordisk, even as other companies quickly close in on their own drug candidates on the way. But even its higher-dose version is expected to face stiff competition.

In a face-to-face trial It has been detected Late last year, Eli Lilly’s tirzepatide (the active ingredient in diabetes drug Mounjaro and obesity treatment Zepbound) outperformed Wegovy, with an average weight loss of 20.2% compared with 13.7%. Other obesity Drugs in development It has also shown early but promising results that may eclipse both tirzepatide and semaglutide.

Another consideration is cost. Current low-dose formulations of semaglutide have been around for years at this point, and their high prices (about $1,000 per month) have angered both The public and legislators. Just this week, the Fed Announce It will schedule both Ozempic and Wegovy for the next round of the recently launched drug negotiation program under Medicare (however, any potential cuts would not take effect until 2027). While a higher dose of semaglutide may be more effective in treating obesity, it would also likely allow the company to continue selling its drug at a similar or even higher price than today’s versions.

The future of obesity treatment looks bright, but it will also be expensive.