GLP-1 Drugs Are Coming in Pill Form

A person is holding two red pills in her hand.

Most of us are aware of injectable GLP-1 drugs for type 2 diabetes and obesity, like Ozempic and Wegovy. However, did you know there are also pill versions of these drugs, with more potentially on the way?

Rybelsus is an oral form of semaglutide, a GLP-1 drug used to treat type 2 diabetes alongside diet and exercise. It is produced by Novo Nordisk, the same company behind Ozempic and Wegovy.

Approved by the FDA for type 2 diabetes since 2019, Novo Nordisk is exploring whether a higher dose of oral semaglutide can be as effective as the weekly injectable Wegovy for weight loss. Eli Lilly is also developing an oral GLP-1 called orforglipron to treat obesity or overweight in adults. Eli Lilly’s phase 2 results show orforglipron, a daily oral nonpeptide GLP-1 receptor agonist, achieved up to a 14.7% mean weight reduction at 36 weeks in adults with obesity or overweight.

Pfizer is entering the oral GLP-1 market with an experimental pill called danuglipron for adults with obesity, intended for daily use rather than the weekly injectables. “Obesity is a key therapeutic area for Pfizer, and the company has a robust pipeline of three clinical and several pre-clinical candidates,” said Mikael Dolsten, M.D., the chief scientific officer and president of research and development at Pfizer.

But will oral GLP-1s change the game and appeal to those turned off by injectables? According to experts, it depends.

Britta Reierson, M.D., a metabolic health and primary care physician and the medical director of Knownwell, said:

I don’t think we’re going to shift away [from injectables] because that wave of interest is already happening… but there needs to be oral options as well… There needs to be a broadened toolkit available because we know that this treatment isn’t one-size-fits-all across the board.

How oral GLP-1s could impact treatment

Oral GLP-1 drugs could improve drug access, especially if refrigeration is an issue, noted Marc-Andre Cornier, M.D., the director of the division of endocrinology, diabetes, and metabolic diseases at the Medical University of South Carolina and president-elect of The Obesity Society. Injectable GLP-1s like Ozempic or Wegovy require proper storage at low temperatures, which can be challenging in certain parts of the world. An oral version could circumvent this issue.

Dr. Reierson added that oral GLP-1s could help address the drug shortage issues common with injectables, as they are generally easier to manufacture. “We need to focus more time and energy on developing GLP-1s in an oral form to make this treatment more sustainable, because there is a crisis in supply and demand with the injectables,” she said.

Aside from supply issues, some people might be deterred by needles or have safety concerns about injections. An oral version of semaglutide could alleviate these worries.

However, Dr. Cornier pointed out that many people who find injectables effective do not mind the needle format and might prefer a weekly injection over a daily pill. For some, a weekly injection could be more convenient than daily medication.

Rybelsus, for instance, must be taken on an empty stomach with no more than 4 ounces of water. Users need to wait 30 minutes before eating, drinking, or taking other oral medications. In contrast, Ozempic can be taken anytime, with or without food.

Cost and side effects remain major factors

Even if the needle is removed, side effects still exist for oral medications. If someone cannot handle the side effects of an injectable GLP-1, an oral pill likely will not solve the problem. “The GI side effects, nausea, vomiting, and constipation…those seem to be across the board. The higher the dosage of the oral medication, the more likely those side effects are,” Dr. Reierson said.

Affordability is also a significant concern. Unless oral medications are significantly cheaper than injectables, access will remain an issue for those needing GLP-1 drugs. Currently, the out-of-pocket costs for Rybelsus are almost the same as for Ozempic.

It makes sense that the drugmakers are rushing to flood the market with currently popular drugs and pave the way for research on new versions in different forms and potency.

Doug Baker, VP of industry relations for The Food Industry Association, said, “In the next few years, we could see anywhere from 12 to 36 million people that could be potentially on this”, noting that FMI has knowledge of 70 different trials in the works at the Food and Drug Administration for new GLP-1 drugs. Also, data gathered from 5,577 U.S. adults in early March for a Gallup poll revealed that 6% of U.S. adults have tried GLP-1 drugs for weight loss, and 3% are currently using them.

Your responses and feedback are welcome!

Source: “Would You Be More Likely to Take GLP-1s If They Came in Pill Form?,” VeryWellHealth.com, 8/6/24
Source: “Nearly a third of U.S. consumers could begin using GLP-1 drugs,” SupermarketNews.com, 8/5/24
Source: “Bernstein poll: 6% of US adults have already tried GLP-1’s for weight loss,” Investing.com, 8/5/24
Image by Kateryna Hliznitsova on Unsplash

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Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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