Will Pfizer's New Weight Loss Pill Silence the Ozempic Commercials?

It would be so delightful, even life-affirming, to get Novo Nordisk's execrable O-O-O-Ozempic TV ad off the air, or even reduce its malevolent presence. While there is no shortage of cringe-worthy TV ads (am I the only one who wants that stupid emu turned into an artillery target?) it would be difficult to pick a more hated 60 seconds of TV than the Ozempic ad.

Perhaps Pfizer can help out. The company just published positive Phase II results of Danuglipron (formerly PF-06882961) in a new JAMA Network article. Danuglipron, like Ozempic, is also a Glucagon-Like Peptide 1 (GLP-1) receptor agonist, but there is a significant difference between the two drugs. As if the commercial isn't painful enough, Ozempic must be injected while Danuglipron is an orally active pill, which offers a significant advantage.

What's in the study?

Danuglipron was evaluated for its ability to:

• Reduce glycated hemoglobin (HbA_1c, the primary endpoint)
• Reduce fasting blood glucose
• Reduce body weight 

and also for:

• Safety

Of course, HbA_1c and weight are both numbers, but people aren't climbing all over each other to get their A_1C numbers down. The real attraction of GLP-1 drugs is they promote significant weight loss, one of the holy grails of pharmaceutical research, and something people, especially celebrities, will pay just about anything to get (1).

Evaluation of Danuglipron

The Phase IIb trial, which was conducted between July 7, 2020, and July 7, 2021, was a double-blind placebo-controlled randomized clinical trial with 411 participants who had poorly controlled type 2 diabetes. The participants were divided into 6 groups: placebo, and Danuglipron at five doses ranging from 2.5-120 mg (given twice per day for 16 weeks).

Efficacy data table.  Modified from JAMA Netw Open. 2023;6(5):e2314493. doi:10.1001/jamanetworkopen.2023.14493 

Summary of Data

Although the table is complex there are some key points that I have highlighted using colors:

• For the primary outcome (HbA_1c), the reduction is statistically significant (yellow box) at all 6 doses.
• For fasting plasma glucose (FPA), the same holds true (second yellow box).
• But for weight loss, there is a statistically significant difference between placebo and drug only at the two highest doses (green box).
• More side effects were present in the group that received the highest (120 mg) dose. This can be seen by the number of participants remaining in the trial (compare the blue and red boxes). This is to be expected since this class of drugs is known to cause nausea, vomiting, and diarrhea. 

What about Ozempic?

Danuglipron was not compared to Ozempic in this trial, but some information can be gleaned from an Ozempic Phase III trial.

• Participants who received a 1 mg injection of Ozempic for 30 weeks lost about 10 pounds, the same as participants who received the highest dose of Danuglipron (120 mg).
• Both drugs reduced HbA_1c – Danuglipron by about 1.2% and Ozempic by about 1.5%.
• The best you can really say now is that the two are similar.

Bottom line

It is not yet possible to directly compare the two drugs (2) since they have not been in the same study. But we can make some approximations, Danuglipron is an orally active small molecule (pill) effective at a dose range of roughly 40-120 mg while Ozempic is a peptide-like molecule, which is given by injection at doses of 0.5 or 1.0 mg. Which company will win? Which is better? This remains to be seen. If it's Danuglipron, perhaps the company's TV ads will be less nauseating. Maybe the drug too.

NOTES:

(1) Said celebrities have helped bring about a shortage of the drug.

(2) It's three really, sort of. Ozempic is the same drug (semaglutide) as Wegovy. The difference is that Ozempic is approved for type 2 diabetes and Wegovy (a higher dose) for obesity. They are both made and marketed by Novo Nordisk. O-O-O-that's sleazy...