April 19, 2024
OASIS and PIONEER PLUS demonstrate the effect of oral semaglutide at high doses

San Diego – Higher doses of oral semaglutide than the currently approved dose of 14 mg/day in type 2 diabetes could be an add-on treatment option for patients with prediabetes, diabetes and obesity. This emerges from the results of two recently published phase 3 clinical trials.

Results from the OASIS 1 study in overweight or obese patients without diabetes and the PIONEER PLUS study in patients with inadequately controlled type 2 diabetes were presented at the 2023 American Diabetes Association (ADA) Scientific Sessions and simultaneously published in The Lancet published [1,2,3].

Dr. Philip K. Button

Dr. Philip K. Button from the University of Copenhagen, Denmark, presented the main results of OASIS-1, e dr. Vanita R. ArodaBrigham and Women’s Hospital and Harvard University, Boston, Massachusetts discussed the key findings of PIONEER PLUS.

OASIS-1 demonstrated that “orally administered semaglutide 50 mg may be an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Knop summarized.

And “the PIONEER PLUS study demonstrated that higher doses of once-daily oral semaglutide (25 mg and 50 mg) than the current [höchsten] The approved dose of 14 mg leads to better control of blood sugar levels and reduction of body weight, as well as an improvement in cardiometabolic risk factors,” added Aroda.

The chairman of the session Dr. Marion PragnellADA vice president of research and science, he said Medscapethat multiple treatment options are needed as different patients respond differently to each drug. The oral dose of semaglutide should be higher than that for subcutaneous injection (Ozempic®, Wegovy®) due to bioavailability. But small molecule research is progressing, so in the future lower doses of oral drugs could have the same effect as the current lower subcutaneous doses of the drug.

dr. Vanita R. Aroda

The oral version of semaglutide (Rybelsus®) was approved in the United States in 2019 for type 2 diabetes at a dose of 7 mg or 14 mg per day; it is not approved for the treatment of obesity. This also applies to Europe.

Knop noted that about 25 percent of his type 2 diabetes patients would prefer to take semaglutide by mouth every day; the rest prefer weekly injections of semaglutide.

Semaglutide 50 mg administered orally may be an effective option for the treatment of obesity, particularly in patients who prefer oral administration.
Dr. Philip K. Button

“The availability of an oral formulation of semaglutide in addition to the subcutaneous or injectable formulation will allow people struggling to lose weight through diet and exercise alone to take this powerful drug in a way that is most convenient for them,” he added.

Participants in the OASIS and PIONEER PLUS studies were instructed to swallow the drug on an empty stomach in the morning with up to one-half glass of water (120 mL) at least 30 minutes before breakfast and before taking any other drugs.

Prof. Dr. Sean Whartonmoderator and crowded speaker at the ADA session where the results were presented, said, “OASIS 1 and PIONEER PLUS introduce the world to a drug that is taken orally, relatively easy to administer, scalable, effective, and similar in efficacy to semaglutide injectable.” Specifically, this is a 15% weight loss after 52 weeks.

Higher doses of… semaglutide… result in better blood glucose control and reduction in body weight, as well as an improvement in cardiometabolic risk factors.
dr. Vanita R. Aroda

Wharton is an assistant professor at the University of Toronto, Ontario, Canada and the lead author of the 2020 Canadian Obesity Guidelines. He was not involved in either study.

OASIS: 50 mg tablet daily in overweight or obese adults

Knop and colleagues state that, to their knowledge, OASIS is “the first study to evaluate the weight-loss effect of an oral GLP-1 agonist (semaglutide 50 mg once daily) in overweight or obese adults without diabetes of type 2”.

The 50 mg dose resulted in a clinically meaningful reduction in body weight and improvement in cardiometabolic risk factors, consistent with results for subcutaneous semaglutide 2.4 mg once weekly (Wegovy®) in a similar population.

These results suggest that taking semaglutide 50 mg orally could be an effective option for overweight or obese people.
Dr Filip K. Knop and colleagues

Oral intake of 50 mg semaglutide in combination with diet and exercise resulted in an average reduction in body weight of 15.1% compared with 2.4% in the placebo group. A higher proportion of participants achieved weight reduction goals of at least 5%, 10%, 15%, and 20%.

This success was accompanied by a significant improvement in cardiometabolic risk factors compared to the placebo group.

“These results suggest that taking semaglutide 50 mg orally could be an effective option for overweight or obese people,” the researchers conclude.

PIONEER PLUS: Poorly controlled type 2 diabetes

Aroda and colleagues report the results of PIONEER PLUS: “In people with inadequately controlled type 2 diabetes on a stable dose of 1 to 3 oral glucose-lowering drugs offered higher doses (25 mg and 50 mg) of oral semaglutide once daily day for more effective glycemic control and greater body weight loss than 14 mg semaglutide without additional safety concerns,” they write.

PIONEER PLUS is the first study to suggest that higher doses of semaglutide may be a highly effective oral option for improving glycemic control and weight loss in type 2 diabetes.

“This study provides compelling evidence that the availability of a broader range of oral semaglutide doses allows for individualized dosing for the desired effect and the ability to escalate treatment as needed,” said Aroda. “We hope these findings advance more effective treatment of type 2 diabetes and allow for more widespread treatment in primary care.”

In an accompanying editorial [4] write Dr. Christina H. Sherrill AND Dr. Andrew Y. Hwang: “This expansion of dose titration could provide clinicians with more opportunities to achieve the maximum efficacy of this oral GLP-1 agonist.”

This expansion of dose titration could provide clinicians with more opportunities to achieve maximum efficacy from this oral GLP-1 agonist.
Dr. Christina H. Sherrill

“However, more research is needed to determine whether the superior blood glucose reduction seen at these higher doses translates into a reduction in cardiovascular risk,” said Sherrill of High Point University in North Carolina and Hwang of the Massachusetts College of Pharmacy and Health. Science University. in Boston. Such studies “would further clarify the value of high-dose oral semaglutide in therapy,” they conclude.

Aroda and colleagues agree: “More studies are needed to investigate the clinical implications of the availability of higher doses of oral semaglutide.”

Where does oral semaglutide fit into the spectrum of therapies?

Speaking at the discussion, Wharton said she saw rapid development of weight-control drugs, high demand, the unavailability of injectables and a “Hollywood phenomenon” that people were taking off-label drugs to shed a few pounds. . Among other things, he alluded to the fact that stars, but also social media influencers, massively spread the preparation.

“Oral semaglutide at doses of 25 mg and 50 mg is effective,” Wharton summarized. The magnitude of mean weight loss in these studies (15%) was the same for oral drugs and 2.4 mg subcutaneous semaglutide. With both formulations, 1/3 of the patients lost more than 20% of the initial weight.

Semaglutide: more treatments worldwide with oral pharma?

Wharton noted that injectable GLP-1 receptor agonists are unavailable to many obese people worldwide. The countries that would market Semaglutide Injectable 2.4mg (Wegovy®) – Norway, Denmark and the United States – were among the wealthiest nations in the world.

A pill could have a wider global reach and improve access to care. Semaglutide 50 mg could be a long-term solution to obesity and reduce associated comorbidities, Wharton said.

What’s remarkable about these studies is that “the company was able to produce a sensational molecule that many people didn’t think would have such a significant impact,” Wharton commented. Medscape.

“For those who can afford to take it, it has a very nice place in general therapy to offer equally effective add-on options.” I also think it’s possible that we have an opportunity to bring new drugs to other people as well,” Wharton said.

Contribution was made by Michael van den Heuvel www.medscape.com translated and adapted.

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