Will Oral Obesity Meds Match Injections?

A pair of reports on Monday raised the possibility that we may soon have oral obesity meds that match the remarkable effectiveness of injections. One of these drugs is an oral formulation of semaglutide that’s already available at a much lower oral dose for diabetes under the brand name of Rybelsus. Novo Nordisk makes it. The other is a totally new drug from Pfizer called danuglipron.

Oral Semaglutide

Of these two oral drugs, we know the most about semaglutide because it’s already available – albeit at a much lower dose than is necessary for treating obesity. Under the brand name of Rybelsus, people use it in doses up to 14 mg once daily for treating diabetes.

But now the data on higher doses for obesity – 25 and 50 mg daily – are coming into view. At the end of March, Novo announced results from the PIONEER PLUS trial of these doses in people with both obesity and diabetes. Yesterday, the company announced results from the OASIS-1 trial of the 50 mg dose in people with overweight or obesity – but not diabetes. This is significant because people with diabetes and obesity typically lose less weight than people with obesity and no diabetes.

The bottom line, according to Martin Holst Lange of Novo Nordisk:

“The results show comparable weight loss as in the STEP 1 trial with injectable semaglutide 2.4 mg in obesity branded as Wegovy.”

In this trial, people lost between 15 and 17 percent of their starting body weight, depending upon adherence to the dosing regimen. In the placebo group, weight loss was only 1.8 percent.


Danuglipron is the new kid on the block and the data that Pfizer published yesterday were only phase 2 results. That means this drug is at an earlier stage, where the purpose of this study was to show that a new, twice daily oral medicine is safe for its intended use. On the plus side, these results were not just a company announcement. Pfizer published their findings with peer review in JAMA Network Open.

This was a short-term study – only 16 weeks. Also, it tested a wide range of doses because the study subjects were being treated for diabetes.  The average BMI was 33, so most of the patients in the study had overweight or obesity. Changes in body weight were secondary outcomes. But despite all these caveats, the changes in weight were entirely respectable – a mean of 5 percent after just 16 weeks.

Much Yet to Learn

It was probably a happy accident for Pfizer that their results came out on the same day as the Novo Nordisk results for the OASIS-1 trial. Sloppy headline writers proclaimed that both drugs work as well in tablet form for obesity as injections like semaglutide.

In truth, the Pfizer data can neither confirm nor refute this. It’s too early to say that. We will need phase 3 data to know how effective danuglipron truly is. Likewise, we need to see the full data on oral semaglutide, peer reviewed and published. We expect to see some of this in June around the time of the American Diabetes Association Scientific Sessions.

Novo Nordisk plans to submit oral semaglutide for FDA approval this year. For Pfizer, submission is at least a few years away. We have much to learn about these drugs.

Click here for the study of danuglipron, here for the announcement from Novo Nordisk on oral semaglutide, here, here, and here for further reporting on these developments.

Tablets, photograph by Ted Kyle / ConscienHealth

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May 23, 2023