Mouth of Akhenaten or Nefertiti

Tab or Jab? Oral Semaglutide for Obesity

While Ozempic and Wegovy – two injectable forms of semaglutide – have been grabbing headlines, an oral tablet form – Rybelsus – has been quietly building momentum. Right now, it’s only approved for use in type 2 diabetes. But on Friday, Novo Nordisk announced results from the first phase 3 study of oral semaglutide for obesity and they are good.


This trial of oral semaglutide aimed to recruit 1,224 patients with overweight or obesity and type 2 diabetes. The goal was compare higher doses that may be needed for obesity treatment – 25 and 50 mg daily – to the standard approved dose for type 2 diabetes, 14 mg daily. Glycemic control was the primary outcome measure, change in body weight was secondary.

On both points, the higher doses were more effective. The reduction in HbA1c was 1.5 percentage points with the 14 mg dose, 1.9 points with 25 mg, and 2.2 points with 50 mg. Weight loss with the 14, 25, and 50 mg doses was 4.7, 7.3, and 9.2 percent respectively. The differences were statistically significant.

It’s important to note that these data are from patients with type 2 diabetes. The importance is because weight loss with obesity meds in this population is typically less than in patients without diabetes. So the 9.5 percent weight loss with the 50 mg daily oral dose appears to be comparable to the results seen in diabetes patients with weekly injections of semaglutide at the 2.4 mg dose of Wegovy.

According to the company, the most common adverse events were gastrointestinal and mostly mild to moderate. They diminished over time, and were consistent with expectations for GLP-1 receptor agonists.

More to Come

This is the first hint of what we might see with oral semaglutide in obesity. A better view will come from the peer-reviewed publication of these results. Even more enlightening will be the presentation of results from the first phase 3 study targeted solely at treating obesity. We expect that in June at the American Diabetes Association meeting when Novo Nordisk plans to unveil OASIS-1 study results. This will be the first of four pivotal trials planned for this indication.

The company said they plan to submit an application for oral semaglutide at these higher doses to FDA this year. In addition, both Pfizer and Lilly are working on oral GLP-1 agonists for obesity.

The options for obesity care are growing.

Click here for the company announcement of these topline results, here and here for additional reporting.

Mouth of Akhenaten or Nefertiti, image from the Metropolitan Museum of Art / Wikimedia Commons

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March 27, 2023