An Oral Version of Wegovy Appears as Effective as the Injectable Version
Fact checked by Nick Blackmer
Key Takeaways
A daily oral version of the blockbuster weight loss drug semaglutide appears to be as effective as the weekly injectable sold as Wegovy.
Drug maker Novo Nordisk shared the data via press release last week.
Oral semaglutide is already available for diabetes treatment under the brand name Rybelsus. The company is seeking a weight loss indication for a higher-dose version of the same drug.
An oral version of semaglutide, the drug marketed as injectables Ozempic and Wegovy, causes substantial weight loss in people with obesity and overweight, according to data shared by drugmaker Novo Nordisk last week. While not yet approved squarely for a weight loss indication, a prescription pill or tablet may soon be a viable option for treating obesity.
Novo Nordisk already sells oral semaglutide for diabetes treatment under the brand name Rybelsus and is now testing a high-dose version for weight loss.
In a study of nearly 700 adults with overweight or obesity, patients taking a daily semaglutide tablet lost 15.1% of their body fat over 17 months, compared to 2.4% among people who were only making lifestyle changes. That puts it on par with Wegovy; the weekly injection caused a 14.9% weight loss over the same period in an earlier study.
Oral formulations, like pills or tablets, could provide more options for patients who are unwilling or unable to self-inject glucose-inhibiting medications.
Related: Who Should Get Weight Loss Drugs? Why People With Obesity Can’t Access Ozempic, Mounjaro
“Just like with other chronic health conditions, it is exciting to be able to offer a variety of different medical options for patients and allow them to select the agents that are going to work best with their lifestyle and their values and preferences,” Edmond Wickham III, MD, MPH, an obesity medicine specialist and associate professor of internal medicine and pediatrics at Virginia Commonwealth University, told Verywell.
Novo Nordisk said it plans to file for Food and Drug Administration (FDA) approval of the drug later this year.
Defining ‘Obesity and Overweight’
For the study, researchers included participants with the following criteria:
A body mass index (BMI) greater than or equal to 27 kg/m2 with the presence of at least one of the following weight-related complications: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease
A BMI greater than or equal to 30 kg/m2
How Does a Tablet Compare to Injectables?
Novo Nordisk tested once-daily oral semaglutide tablet in 667 people with obesity or overweight with at least one comorbidity.
When looking at people who perfectly adhered to the treatment, researchers saw weight loss of 17.4% over 68 weeks compared to a 1.8% reduction in the placebo group.
Nearly 90% of those taking oral semaglutide lost 5% of more of their weight after 68 weeks, compared to 24.5% in the placebo group. That’s slightly more than those taking injectable Wegovy.
Popular weight loss or diabetes drugs Wegovy, Ozempic, Mounjaro, and Rybelsus are all glucagon-like peptide-1 receptor (GLP-1) agonists. Rybelsus, the low-dose semaglutide tablet by Novo Nordisk, was the first drug in this class to be given orally.
Rybelsus is currently available in dosages of 3, 7, and 14 milligrams (mg) for treating type 2 diabetes. In the latest study, the company tested a 50-mg dose for weight loss.
Related: What's the Difference Between Ozempic, Wegovy, and Mounjaro?
Side Effects
So far, side effects of a tablet appear similar to side effects of injections. As with all glucose-lowering medications, oral semaglutide can come with gastrointestinal side effects, like nausea, abdominal pain, and vomiting. Novo Nordisk said patients most commonly experienced these adverse events when their dosage was increased.
The company hasn’t yet shared the full results of its clinical trial data. Because the dosage is more than three times greater than the current highest Rybelsus option, Wickham said it’s possible that the weight loss drug would come with greater side effects.
Raoul Manalac, MD, an obesity medicine specialist and Senior Director of Clinical Experience for Ro’s Body Program, said he’s looking forward to reading the full study results to learn more about how a high-dose oral semaglutide compares to a high-dose injectable version.
“Without a true head-to-head trial, data on the incidence and degree of side effects with high-dose oral semaglutide treatment can at least give us some insight into how patients’ experiences might compare to those using the injectable form, helping patients and providers choose the best option for each individual,” Manalac said.
Related: Mounjaro Generic May Soon Join Wegovy as a Weight Loss-Approved Drug
Opening Options for Patients
If approved, the oral semaglutide could improve weight-loss options for people who prefer not to self-inject the drug.
But oral semaglutide comes with its own limitations. For the drug to be properly absorbed, it must be taken on an empty stomach, an hour before taking other medications and half an hour before eating.
If a person takes the drug alongside food, only small amounts of the drug will be absorbed and it could lose substantial efficacy, said Daniel Drucker, MD, FRCPC, an expert in diabetes and obesity treatments and senior investigator at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada.
“Some people get up in the morning and they don’t get around to having their coffee or breakfast for 45 to 60 minutes and it fits into their routine, whereas other people might say, ‘the moment I get up, I’m starving, I need to have a coffee, and I don’t want to wait 60 minutes,’” Drucker said. “I think more flexibility is always a good thing for people.”
Wickham said that in most cases, the choice to take semaglutide orally or via injection will come down to patient preference. He said the injections haven’t proven to be too great a barrier to use, and he doesn’t expect oral semaglutide to overtake injectable versions of weight loss drugs if it proves to be more effective.
In rare instances, patients may experience allergic reactions at the site of the injection. Wickham said that for most people with dermatologic diseases, like eczema and psoriasis, patients are usually able to find places to self-inject that don’t cause pain.
“I have had a handful of patients that have had some site reactions with the injectable semaglutide and then switched to Rybelsus and did not have any problem with that,” Wickham said. “They were able to experience some of the benefits of the medication without concerns about the local reaction with the injection.”
Manalac said that drugmakers have come a long way in creating self-injection pens that can be used “fairly comfortably.” Still, there are likely to be many patients who are turned off by the idea of injections.
“The availability of a highly effective, oral semaglutide unlocks the opportunity for life-changing diabetes and weight management for a significant number of people who might not have pursued it otherwise,” Manalac said.
What This Means For You
Some people will prefer an oral version of semaglutide, while others may be able to better adhere to a weekly injection. Talk with a healthcare provider about your lifestyle and which weight loss regimen is right for you.
