The race to develop even more effective anti-obesity drugs is heating up. This week, Novo Nordisk announced that people taking its megadose version of semaglutide lost significantly more weight than normal in a large trial.
Novo Nordisk’s STEP UP trial included more than 1,400 obese people, 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 baseline weight over a 72-week period. The findings exceed the typical weight loss results seen with existing semaglutide-based drugs Ozempic and Wegovy.
Semaglutide mimics the hormone GLP-1, which helps regulate our hunger and metabolism. It is an active ingredient in the type 2 diabetes drug Ozempic and the higher-dose obesity drug Wegovy. Since Wegovy was approved by the FDA in 2021, Ozempic is often prescribed for unspecified weight loss. In large, placebo-controlled trials of Wegovy, people lost about 15% of their body weight, well above the average weight loss seen with diet and exercise or with older obesity drugs.
The advent of semaglutide opened a new era of obesity treatment. Both Novo Nordisk and its competitors have invested efforts in developing the next generation of these drugs. Although Wegovy is already a higher-dose formulation of semaglutide (its maximum prescribed dose is 2.4 milligrams, compared to Ozempic’s maximum dose of one milligram), the company relies on the fact that the drug’s effectiveness has not yet reached its upper limit.
The STEP UP trial included three groups: people who either received a placebo, Wegovy’s 2.4-milligram dose of semaglutide, or a 7.2-milligram dose.
When looking at people who fully adhered to the medication schedule (weekly injections under the skin), those on the 7.2 milligram dose lost an average of 20.7% of their body weight after 72 weeks, compared to 17.5% lost of body weight for the 2.4 milligram group, and 2.4% of body weight lost for the placebo group. Even when non-adherent people were included, the higher-dose version still outperformed the original (18.7% 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 receiving 7.2 milligrams had side effects that were comparable to the group receiving the lower dose, 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 disappear over time. Much less often, scientists associate GLP-1 drugs with 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 established with Wegovy,” said Martin Holst Lange, Executive Vice President Development at Novo Nordisk, in statement from the company.
The company will also soon announce the results of its STEP UP T2D trial, which tested a 7.2-milligram dose in people with obesity and type 2 diabetes. Assuming things go according to plan, semaglutide will likely have an extended shelf life as a top treatment for obesity and diabetes for Novo Nordisk, even with other companies rapidly approaching with their own drug candidates on the way. But even its highest-dose version is expected to face stiff competition.
In direct trial exposed late last year, Eli Lilly’s existing drug tirzepatide (the active ingredient in diabetes drug Mounjaro and obesity treatment Zepbound) outperformed Wegovy, with an average of 20.2% weight loss compared to 13.7%. Other obesity drugs in development also showed early but promising results that could eclipse both tirzepatide and semaglutide.
Another consideration is price. Current lower-dose formulations of semaglutide have been around for years at this point, and their high prices (about $1,000 per month) have angered and the public and legislators. Just this week, the federal government announced that it will schedule both Ozempic and Wegovy for the next round of its recently debuted Medicare drug negotiation program (all potential cuts won’t take effect until 2027, however). While a higher dose of semaglutide might be more effective in treating obesity, it would also likely allow the company to continue to sell 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.