Are Pills the Next Big Thing for GLP-1 Drugs? …C0NTINUE READING HERE >>>
Key Takeaways
Several drugmakers are working on oral GLP-1s, offering people with obesity and overweight more options than the injectables on the market.Experts say oral options could help with supply issues, and possibly appeal to people who don’t like injections.Unless oral versions of GLP-1s are more affordable than injectables for patients, access will likely remain a barrier.
Most of us know that there are injectable GLP-1 drugs for type 2 diabetes and obesity, sold under brand names such as Ozempic and Wegovy. But did you know there are also pill versions of this class of drug—and there might be more on the way?
Rybelsus is an oral version of semaglutide, which is a type of GLP-1 drug. It’s used to treat type 2 diabetes along with diet and exercise, and is made by Novo Nordisk, the same drugmaker of Ozempic and Wegovy.
While Rybelsus has been FDA-approved for type 2 diabetes since 2019, Novo Nordisk is looking at whether a higher dose of oral semaglutide is as effective as the weekly injectable Wegovy for weight loss. Eli Lilly is also working on an oral once-daily GLP-1 called orforglipron to treat obesity or overweight in adults.
Pfizer is jumping into the oral GLP-1 market, too. The drugmaker recently announced it’s moving forward with an experimental pill called danuglipron for adults with obesity. This drug is to be taken daily, rather than the weekly regime of injectables.
“Obesity is a key therapeutic area for Pfizer, and the company has a robust pipeline of three clinical and several pre-clinical candidates,” Mikael Dolsten, MD, the chief scientific officer and president of research and development at Pfizer, said in a statement about the new drug.
But will oral GLP-1s change the game, and possibly appeal to people who might be turned off by injectables? According to experts, it depends.
“I don’t think we’re going to shift away [from injectables] because that wave of interest is already happening…but yet, there needs to be oral [options] as well,” Britta Reierson, MD, a metabolic health and primary care physician and the medical director of Knownwell, told Verywell. “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 help improve drug access, especially if refrigeration is an issue, Marc-Andre Cornier, MD, 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, told Verwywell.
Because injectables such as Ozempic or Wegovy need to be stored properly at low temperatures, an oral version of the drug could be used by people in parts of the world where proper storage conditions are a challenge.
Reierson added that more oral GLP-1s might also help address drug shortage issues that have been common with injectables, as they can be easier to manufacture. “We need to focus more time and energy in 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,” Reierson said.
Aside from supply issues, some people might be turned off by needles or have concerns with the safety of injections. An oral version of semaglutide could help mitigate that.
According to findings from a recent Verywell Health survey about obesity and obesity drugs, only 1 in 5 respondents took medication for obesity/overweight. While 76% of those people think the drugs are effective, only 36% think they’re safe.
Reierson said that oral GLP-1s might indeed help people with needle phobia, or offer those who prefer to take pills the option to do so.
Research shows that there is a desire for pill GLP-1s. A 2021 study on whether those with type 2 diabetes prefer an oral tablet or injectable medication found that preferences were split nearly 50/50, indicating there’s not a “one‐size‐fits‐all approach” when it comes to people’s preferences.
However, according to Cornier, most people who use an injectable and find it effective often don’t have a problem with the needle format and might be more inclined to take a weekly injection rather than a daily pill. For some people, administering medication once a week could be easier than taking it daily.
Rybelsus, for instance, needs to be taken when you first wake up on an empty stomach with no more than 4 ounces of water. People need to wait 30 minutes after taking the pill before they can eat, drink or take other oral medications.
Ozempic, on the other hand, can be taken at any time, with or without food.
Better Efficacy Will Mean Better Uptake
A change in behavior could happen if new oral medications hit the market and are shown to be as or more effective than the current injectables, said Diana Thiara, MD, an assistant professor of medicine at the University of California San Francisco (UCSF) medical center and the director of the UCSF Weight Management Clinic.
“If the medications have the same rates of weight loss, the same side effects profile, people probably—just on the surface—would prefer an oral option as it’s more familiar and it sounds less daunting,” Thiara said. “But I think there would still be a market for injectables for people who find that easier.”
While Rybelsus is currently available in dosages of 3, 7, and 14 milligrams (mg) for treating type 2 diabetes, the drugmaker is testing a 50-mg dose for weight loss.
According to a study on the higher-dose drug, adults with obesity or overweight taking the daily tablet lost 15.1% of their body fat over 68 weeks. That finding put the pill on par with Wegovy, as a separate study found that people taking the injection lost 14.9% of their body fat over the same period of time.
“Their initial outcome data looks very promising, and very comparable to the injectables,” Reierson said. “That’s always been the question: Is it comparable? Is the efficacy as good as the injectable medications?”
Cost and Side Effects Remains Major Factors
Even if drugmakers remove the needle, side effects still exist for oral medications. That means if someone can’t handle the side effects of an injectable GLP-1, an oral pill likely won’t solve the problem.
“The GI side effects, nausea, vomiting, and constipation…those seem to be across the board. I think the higher the dosage of the oral medication, the more likely those side effects are,” Reierson said.
Concern around affordability is also top of mind, said Thiara. Unless the cost of oral medications is significantly lower than injectables, access will still be a concern for people who use and need GLP-1 drugs.
“The out-of-pocket costs for Rybelsus is almost the same as for Ozempic,” Thiara said.
At the moment, taking Rybelsus requires certain adherence conditions, such as taking the pill on an empty stomach, Thiara said. The newer oral medications should ideally account for that and make it easier for people to take them. (Both Pfizer’s and Eli Lilly’s experimental oral drugs currently don’t have dietary restrictions.)
“The question really is, are the companies that are working on newer drugs going to be able to come up with formulations that are not the same as the current Rybelsus?” Thiara said. “Because that’s not cheap, and it’s not an ‘easy’ medication to take.”
What This Means For You
Drugmakers are in the process of developing new oral GLP-1s that aim to be as effective or more effective as the injectables currently on the market. While experts say these oral medications have potential, it’s important to wait and see more information about their efficacy and cost.
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