Orforglipron: The New Oral GLP-1 Agonist

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I have great news for those who dislike needles or prefer a daily reminder to engage in positive behaviors. There’s a new oral GLP-1 molecule making its way to market called Orforglipron!

Currently, Rybelsus is the only oral GLP-1 available, approved for diabetes management up to a dose of 14mg once daily. Rybelsus contains semaglutide, found in Ozempic and Wegovy, but it’s not yet approved for weight management. Trials with 50mg once daily have shown results similar to injectable Wegovy, with a 15% weight loss from baseline. However, Rybelsus needs to be taken on an empty stomach, at least 30 minutes before food or other medications—a bit inconvenient.

Orforglipron, on the other hand, is a game-changer. It’s an oral nonpeptide GLP-1 receptor agonist that can be taken without regard to food, drink, or other medications. It’s designed to be absorbed easily through the digestive tract, without needing an absorption enhancer like Rybelsus. This makes it much more convenient for daily use.

So, how effective is Orforglipron? 

Let’s dive into the Phase 2 RCT study. This preliminary trial involved 272 participants with obesity, split into groups receiving either 12mg, 24mg, 36mg, or 48mg of Orforglipron daily, or a placebo. Participants received basic counseling on healthy eating and exercise.

The study found that participants, who were mostly female with an average age of 54, weight of 108.7kg, and BMI of 37.9, saw impressive results. Those on 45mg daily of Orforglipron lost 14.7% of their baseline weight after 36 weeks, and the weight loss trend hadn’t plateaued yet. For reference, this is comparable to results from the OASIS Trial with oral semaglutide at 50mg daily, which led to a 15.1% weight loss after 68 weeks.

Safety-wise, the side effects were typical for GLP-1 receptor agonists: nausea, vomiting, diarrhea, and constipation. Nothing out of the ordinary here.

Orforglipron is a promising new oral GLP-1 RA that might offer a more convenient and potentially more effective option for weight management. Its smaller molecule size might also mean a cheaper alternative, though time will tell. Plus, more options could help alleviate current drug shortages—exciting times ahead!

Remember, small tweaks lead to massive peaks. Thanks for watching and I’ll catch you next week! 

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Watch my previous videos to learn how to fight obesity and about the best medicine for weight loss: 
▪️ Watch This Before Taking Mounjaro  
▪️ From Ozempic to Mounjaro 
▪️ Muscle Loss with Ozempic, Wegovy & Mounjaro 
▪️ Managing Nausea from Ozempic, Wegovy and Trulicity!  
▪️ Ozempic: Stomach Paralysis Update  
▪️ How to Switch from Ozempic (or Wegovy) to Mounjaro  
▪️ Ozempic Paralyzed My Stomach 
▪️ How to Inject Mounjaro: step-by-step tutorial

Live in Alberta? Come see me at my Pharmacist-led Obesity Clinic at Apothecare Pharmacy – http://apothecarerx.ca 

Products I recommend to support your weight-loss journey: 
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▪️ Managing Diarrhea 
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▪️ Internalized Weight Bias 
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▪️ Activity Trackers  
▪️ My favorite Books 

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Dr. Dan

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