Topline
Novo Nordisk, Eli Lilly and Pfizer have all entered the race for FDA approval of a first-in-class oral weight loss and diabetes drug, and because pills are cheaper to manufacture, these oral weight loss drugs may signal a more affordable (and easier) alternative to drugs—like Ozempic, Wegovy and Mounjaro—that require injections.
In this photo illustration, pharmaceutical pills and capsules seen displayed.
Key Facts
Known generically as semaglutide, Ozempic and Wegovy—both manufactured by Novo Nordisk—are weekly injections and glucagon-like peptide-1 (GLP-1) receptor agonists (a class of drugs used to treat diabetes).
Wegovy was approved by the Food and Drug Administration for weight loss in 2021 and while Ozempic is only FDA approved for use in type two diabetics, doctors regularly prescribe it off-label for weight management.
The popularity of both medications caused a supply shortage, with Novo Nordisk limiting Wegovy’s distribution of lower doses earlier this month to combat supply problems.
Manufactured by Eli Lilly, Mounjaro (known generically as tirzepatide) is a weekly injection and also a GLP-1 receptor agonist, which works by controlling blood sugar—it was approved for use in type two diabetics by the FDA in May 2022, though it’s also used off-label for weight loss.
The heightened popularity of weight loss medications has caused an increase in investor interest in the weight loss treatment market, which is estimated to reach $100 billion by the end of the decade.
News Peg
On Sunday, Novo Nordisk presented findings from a new phase three trial that focused on oral semaglutide tablets. The study, published in the Lancet, lasted 68 weeks and followed 667 participants. 85% of the participants who took the semaglutide tablet lost at least 5% of their body weight compared to just 26% of those who took the placebo. On average, participants who took semaglutide saw a loss of about 15% of their body weight, around six times more than the placebo.
Big Number
69.9%. That’s how many Americans are either obese or overweight, according to data from the Harvard School of Public Health.
Rybelsus
Rybelsus is manufactured by Novo Nordisk (which also makes Ozempic) and is a once-daily oral version of semaglutide. The drug was FDA approved in 2019 for type two diabetes management and became the first GLP-1 receptor drug to gain approval for type two diabetics. In a late-stage study released Monday, the manufacturer released the results from a 68-week trial with 667 adults who are either obese or overweight with one or more comorbidity. On average, participants lost 15.1% of their body weight after 68 weeks compared to 2.4% of body weight from those on the placebo. The results are similar to those from a Wegovy study published in The New England Journal of Medicine. In that trial, participants saw an average change of body weight of 14.9% compared to a 2.4% change in the placebo group over a span of 68 weeks. The Rybelsus study, which has not been published in a peer-reviewed journal, acknowledged the side effects were comparable to the semaglutide injections, with mainly mild to moderate gastrointestinal adverse events (like nausea or diarrhea) being the most common side effect. These adverse events mainly occurred when the dosage was increased. Novo Nordisk plans to “file for regulatory approval in the US and the EU” this year with availability depending on manufacturing capacity and how it prioritizes its medications. Martin Holst Lange, executive vice president for development at Novo Nordisk said in the study the ability for consumers to pick between a once daily oral pill and weekly injection for obesity “has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences.”
Danuglipron
Pfizer published a study in JAMA Network Open on the effects of the drug danuglipron in type two diabetics. Similar to rybelsus, the drug is an oral GLP-1 receptor, but it’s taken twice daily as a pill. The trial included 422 people with type two diabetes and found danuglipron not only lowered blood sugar and hemoglobin A1C at all doses, but it also reduced body weight at the highest dosage. Participants on the 80 milligram pill saw weight loss of 4.5 pounds and those on the 120 milligram pill experienced weight loss of 9.2 pounds by the 16 week mark. The pill was administered to participants once in the morning and once in the evening, both times with food. The most common side effects were nausea, vomiting and diarrhea. Pfizer’s CEO Albert Bourla also explained the importance of an oral obesity pill at J. P. Morgan’s Health Conference, saying it’s “significantly more important…in the obese market than it is in the diabetic population.” Pfizer is also testing another oral medication called lotiglipron (though data isn’t available yet), but the company plans to choose only one of the drugs to advance into late-stage clinical trials in both diabetes and obesity, slated to begin in 2024, Barron’s reports.
Orforglipron
Eli Lilly (the manufacturer of Mounjaro), has its own oral GLP-1 drug, orforglipron, that according to Eli Lilly, shows people without type two diabetes seeing weight reduction between 14% and 15% over the course of 36 weeks, whereas those with type two diabetes saw weight loss of about 9.6% over the same time frame. Orforglipron is in two trials slated to end in 2025, according to information posted on the U.S. National Library of Medicine’s Clinical Trials website. Evaluate Vantage reports Eli Lilly admitted orforglipron won’t be as powerful as Mounjaro because the former is just a GLP-1 receptor agonist, whereas Mounjaro is a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide (GIP) receptor drug. GIP is a hormone that helps with the release of insulin after food consumption. GIP receptors have been reported to reduce weight gain and cause weight loss in animals including nonhuman primates. According to a study published in The New England Journal of Medicine, participants lost up to 22.5% of their body fat after 72 weeks on Mounjaro. Orforglipron’s side effects haven’t yet been made available, but Mounjaro’s most common side effects include nausea, diarrhea, vomiting, constipation, stomach pain and indigestion.
Tangent
According to a study published in the Australian Prescriber that compares oral antibiotics to injectable antibiotics, it was found oral drugs were cheaper to manufacture than the injectable ones. A report published in Health Affairs estimated the cost of oral medication rose by 9% between 2008 and 2016, whereas injectable drugs rose by 15% in the same time frame. This signals the potential approval of oral weight loss medication may be a cheaper, more affordable option than the already available injectables.
Further Reading
Wegovy Shortage: Drug Maker Limits Distribution—Here’s When Supplies Should Improve (Forbes)
