Topline
Competition in the race to crack the lucrative weight loss drug market is heating up as rivals like Roche, Eli Lilly, Novo Nordisk and Pfizer develop oral medications that help people shed weight without an injection, a boon in the fight against obesity but a milestone experts say faces obstacles and is unlikely to eliminate the need for shots entirely.
Key Facts
Blockbuster injections like Ozempic, Wegovy, Mounjaro and Zepbound—brand names for the drugs semaglutide and tirzepatide—belong to booming class of medicines known as GLP-1 agonists, which mimic the action of a hormone involved in regulating blood sugar and appetite called glucagon-like peptide-1.
Drugs made from peptides and proteins—which are essentially very large peptides—are almost always delivered as injections because they are easily broken down by enzymes in the gut and don’t enter the bloodstream easily, particularly when they are large.
“Unless you can prevent the degradation process and also enhance absorption of the protein, you have obstacles to get useful drug levels,” University of Toronto endocrinologist Daniel Drucker told Forbes, adding that “99% of all protein therapeutics” like insulin are injectable.
Though it can be challenging to find a formulation that works as well as an injectable, it can be done, with Novo already marketing Rybelsus, a pill form of semaglutide—the drug inside Wegovy and Ozempic—for diabetes and firms like Lilly and Pfizer making progress on small molecule GLP-1 agonists like orforglipron and danuglipron that can be delivered orally and appear to rival the weight loss achieved with injections already on the market.
Director of West Virginia University’s medical weight management program Laura Davisson told Forbes that weight loss pills may not be for everyone, explaining that adherence tends to fall with the frequency of doses—especially if it needs to be taken more than once a day—and that dietary limitations or restrictions, such as having to take it on an empty stomach, can lessen a drug’s appeal further.
In the end, “some people may prefer a weekly dose, even if injectable,” said Eduardo Grunvald, a professor and the director of weight management program at the University of California San Diego Health.
Will Oral Weight Loss Drugs Replace Injectable Medicines?
Data from clinical trials suggest oral drugs compare favorably to injected weight loss medicines and could potentially offer a similar degree of weight loss with a similar set of side effects. It’s possible companies developing them could opt for lower degrees of weight loss to mitigate side effects or more-than-once-a-day dosing schedules required to overcome difficulties getting the drug into the bloodstream. Even if a pill is less effective at producing weight loss than available injectables, it will still find a market. “We need all the tools we can get to treat obesity,” Davisson said, adding: “A medicine that has a unique characteristic such as being oral, would still be useful, even if it is less effective in terms of weight loss than an injectable GLP1 medication.” Oral medication also eliminates many of the negatives associated with injectable medicines. For example, injector pens can drive up manufacturing costs and often need to be refrigerated, which can limit access. While many patients don’t mind injector pens, Stanford endocrinologist Sun Kim told Forbes “injections can be very daunting for other patients” and these patients could benefit from having an oral option.
When Will Weight Loss Pills Be Available?
Weight loss pills are likely to be years away given the lengthy process of testing medicines.
Ozempic and Wegovy maker Novo Nordisk is ahead of the pack when it comes to getting an oral weight loss drug to market. The Danish giant is the maker of the only authorized oral GLP-1 drug, Rybelsus, and has a sizable first-mover advantage when it comes to securing approval for another condition. Novo cannot launch the drug as a weight loss pill without risking its leading position with its diabetes and weight loss bestsellers Ozempic and Wegovy. Rybelsus is simply an oral formulation of the same drug, semaglutide, and the company is already failing to produce enough to meet demand. Compounding the issue is dosing, with the oral version requiring much more of the active ingredient than the injectable counterpart. Novo has already delayed asking regulators to approve the drug for weight loss and is conducting clinical trials to test a lower-dose version using less semaglutide. Lilly and Pfizer are both working on promising once-daily pills, orforglipron and danuglipron, and Roche has touted promising results from two candidates in early-stage trials.
Tangent
Weight loss pills could also help overcome the often-forgotten environmental impact of injectable medicines, Kim said. “I do worry about the environmental waste associated with injection therapies. Many of the GLP-1 medications use one “pen” for one dose of medications injected weekly,” Kim explained. “That’s 52 pens wasted and dumped in the environment! Hopefully, newer formulations can be mindful of how we can reduce this waste.”
Chief Critic
“Oral medications would be much cheaper for patients and I think would make less money for the companies making it,” said Shauna Levy, an obesity medicine specialist at Tulane University School of Medicine. She added that companies have already “proven they can make an effective” oral version of GLP-1 medications. “I think this is one of the main reasons they are not currently pushing for oral semaglutide and saving all the semaglutide of injectable medication.”
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