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A new once-a-day pill in development may be just as powerful as the injectable medication Ozempic for type 2 diabetes and obesity, according to a phase two clinical trial. And it may work even faster.
Though Novo Nordisk’s injectable diabetes drug semaglutide (Ozempic) has taken the world by storm, another pharmaceutical giant, Pfizer, is developing its own drug in the same family of GLP-1 receptor agonists.
Learn More About GLP-1 Receptor Agonists at Diabetes Daily
Its name is danuglipron, and it’s arguably the most user-friendly formulation yet. It could be a blockbuster.
The new drug passed a major hurdle this week when the results of its most significant trial to date were published in the medical journal JAMA Network Open. This early look suggests that danuglipron is just as safe and powerful as other drugs in the GLP-1 family, including Ozempic.
It will likely be a few years before danuglipron can be approved and sold in the United States, but some experts are already declaring that the new drug will be a game changer that will earn billions of dollars annually, per an article published in Fierce Pharma. There could be millions of adults with type 2 diabetes or obesity that are eager to try a GLP-1 receptor agonist, but would prefer not to inject themselves, and would strongly prefer an easy-to-use daily pill. Pfizer stock prices immediately jumped after the results were published.
How Well Does Danuglipron Treat Type 2 Diabetes?
The experiment tested danuglipron in 411 adults with type 2 diabetes. Most participants took metformin, and all had an A1c between 7 and 10.5 percent, which the study defined as “inadequately controlled.” (A1c is a measurement of average blood sugar levels.) The American Diabetes Association recommends most adults with diabetes to target an A1c of less than 7 percent.
At the highest dosage level, danuglipron users experienced the following metabolic benefits:
- A1c dropped by 1.16 percentage points
- Fasting plasma glucose dropped by 33 miligrams per deciliter (mg/dL)
- Weight dropped by 4.17 kilograms (kg), or 9.2 pounds (lbs)
Remarkably, these results took place over only 16 weeks.
How does that compare with Ozempic? The first pivotal trial of subcutaneous semaglutide, the treatment that would eventually be named Ozempic, delivered slightly more impressive results: an A1c drop of 1.55 percentage points and weight loss of 4.53 kg (9.99 lbs) in a similar population. But this trial lasted 30 weeks, not 16, making it an apples-to-oranges comparison. (A subsequent trial also established that a larger dose of Ozempic over a longer period of time was even more effective).
Danuglipron Versus Rybelsus for Diabetes and Weight Loss
There is already an oral form of semaglutide, a daily pill with the brand name Rybelsus. While Rybelsus appears to be just as powerful as Ozempic, ounce for ounce, it has a notable drawback. Rybelsus is something of a hassle to take — it must be swallowed on an empty stomach exactly 30 minutes before eating or drinking anything other than water, and before using any other oral medications. Danuglipron can be taken with or without food, and therefore may be a more user-friendly therapy.
Danuglipron appears to be no less powerful than Rybelsus, though the published results require some interpretation.
In the PIONEER 2 trial, six months of the highest dose of Rybelsus helped people with type 2 diabetes drop their A1c drop 1.3 percentage points. After one year, study participants had lost about 10 lbs. Those numbers are roughly comparable with the results that danuglipron achieved in only four months, but there remains a possibility that danuglipron users would have enjoyed even greater weight loss or glycemic improvement if they had continued to take the drug for 6 to 12 months.
Novo Nordisk may soon ask the FDA for approval of larger doses of Rybelsus, which a recent study has shown leads to more impressive metabolic improvements.
Danuglipron May Have Side Effects
If there’s bad news, it’s that danuglipron’s side effects appear to be considerable. At the highest dosage, participants reported the following effects, among others:
- 32 percent of users reported nausea
- 25 percent reported vomiting
- 10 percent reported diarrhea
Nearly half of all participants reported at least one episode of gastrointestinal disorder, and 34 percent discontinued the study medication because of a “treatment-emergent adverse event.”
While these numbers look concerning, they aren’t necessarily surprising. Other GLP-1 receptor agonists, especially the blockbuster semaglutide, are associated with similar gastrointestinal effects, per Diabetes Daily. Some Ozempic users have even begun to experiment with custom doses to alleviate their suffering, Diabetes Daily notes.
And people have already shown that they’re willing to tolerate a high prevalence of these uncomfortable effects, given the magnitude of the health benefits and weight loss. The maximum-strength dosage of semaglutide available, for example, has substantially higher rates of gastrointestinal side effects than danuglipron: According to a trial published in the The New England Journal of Medicine, 44 and 32 percent of users report nausea and diarrhea, respectively.
For now, it appears that danuglipron may cause a higher rate of side effects than Rybelsus. The JAMA Network Open study suggests that a more gradual dose escalation schedule could help improve danuglipron’s tolerability, although it might also slow down the noteworthy speed with which it appears to deliver its positive results.
The drug appears to be otherwise safe.
When Will Danuglipron Be Approved?
Danuglipron still has its biggest tests ahead: phase three clinical trials, which will subject the drug to its most comprehensive evaluations yet. These trials last a year or longer and can enroll thousands of participants in order to learn as much as possible about the drug’s long-term safety and efficacy.
If danuglipron has surprisingly good or bad cardiovascular effects, as discussed in a recent study, for example, it could propel the drug to the forefront of treatment — or scuttle Pfizer’s plans for it entirely.