Oral Semaglutide Cuts Body Weight by Over 20% in New Trial
Oral semaglutide cut body weight by up to 16.6% in Phase 3 trial, showing promise as the first pill-based GLP-1 therapy.
Millions of people with obesity avoid treatment because current GLP-1 drugs are only available as injections.
Results from a Phase 3 trial show that a daily oral pill version of semaglutide from Novo Nordisk – produced weight loss of up to 16.6% over 64 weeks.
Why an oral semaglutide is needed in obesity treatment
Obesity is a serious, chronic disease that arises from complex interactions between genetics, environment and biology. People with obesity have higher risks of cardiovascular disease, type 2 diabetes and osteoarthritis. Effective treatment must go beyond diet and exercise; long-term strategies are needed to manage both weight and comorbid conditions.
Currently, injectable GLP-1 receptor agonists, such as semaglutide – marketed as Wegovy® –, have proven effective for weight management. In trials, 2.4 mg of semaglutide weekly has led to average weight reductions of 14–17% in people that are overweight or have obesity.
“Less than two percent of individuals with obesity in the US receive obesity medication,” said Dr. Martin Holst Lange, chief scientific officer and executive vice president of Research & Development at Novo Nordisk.
Oral GLP-1 therapies for weight loss do not yet exist; all approved medicines in this class of drugs require injections. Many patients resist or avoid injectables, resulting in a strong demand for an effective oral option.
Oral semaglutide delivers significant weight loss in Phase 3 trial
The OASIS 4 trial tested is oral semaglutide 25 mg, a once-daily tablet branded as “Wegovy in a pill” and currently under US Food and Drug Administration review. It was designed to match the weight-loss efficacy of the already-approved injectable version.
The study was a Phase 3, randomized, double-blind and placebo-controlled trial. It enrolled 307 adults with obesity or who were overweight who also had at least 1 weight-related health condition. Participants were assigned to take either oral semaglutide 25 mg or placebo for 64 weeks, alongside lifestyle changes such as diet and activity. The treatment schedule included a 12-week dose escalation.
“The oral semaglutide 25 mg data show compelling efficacy for an oral weight management medication and a safety and tolerability profile consistent with injectable Wegovy,” said Lange.
Among those who followed the treatment as prescribed, average weight loss reached 16.6% with semaglutide compared to 2.7% with placebo. More than a third (34.4%) of treated participants lost at least 20% of their body weight, vs 2.9% with placebo.
When all participants were included regardless of how closely they followed the regimen, average weight loss was 13.6% with oral semaglutide vs 2.2% with placebo, and 29.7% of patients lost at least 20% of their weight compared with 3.3% on placebo.
The trial also showed improvements in cardiovascular risk factors and daily physical function.
The safety profile of the oral drug was also in line with the injectable version. The most common side effects were nausea (46.6%) and vomiting (30.9%), generally mild and temporary. Treatment discontinuation was similar between drug and placebo groups (6.9% vs 5.9%). Serious adverse events were less frequent with the drug (3.9%) than placebo (8.8%).
What oral semaglutide could mean for future obesity care
If approved, oral semaglutide could change access to weight-loss treatments. Many people with obesity are unwilling to use injections, and an oral version may encourage more patients to try medication. This would be the first oral GLP-1 therapy for obesity.
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“Wegovy in a pill may address patient preference for oral treatment. Pending FDA approval, ample supply will be available to meet the expected US demand as we hope to set a new treatment benchmark for oral weight loss medications for people with overweight or obesity,” said Lange.
The company submitted a New Drug Application to the FDA earlier this year, with a decision expected by the end of 2025. Manufacturing is already underway at expanded US facilities to avoid shortages.
However, several questions remain. The drug is not yet approved, and its safety and efficacy are still under review. The trial excluded people with diabetes, and results may not apply to all groups. Gastrointestinal side effects were common, and patients stopped treatment because of them. The durability of weight loss beyond 64 weeks is also unknown.
Further trials will look at use in people with diabetes, adolescents and other high-risk groups. There is also interest in confirming cardiovascular and metabolic benefits and monitoring for rare long-term risks such as thyroid tumors seen with injectable semaglutide.
“The OASIS 4 trial results further underscore the significant impact that semaglutide can have in achieving sustainable weight loss and broader health benefits,” said Dr. Sean Wharton, lead author of the study and medical director of the Wharton Medical Clinic.
“Oral semaglutide 25 mg builds on the proven efficacy and established safety and tolerability profile of semaglutide and represents a significant advancement in obesity treatment. People with overweight or obesity have individual preferences, and with oral semaglutide as a potential new treatment option, more of those who are not on treatment today may consider starting GLP-1 treatment,” he added.
This article is a rework of a press release issued by Novo Nordisk. Material has been edited for length and content.
