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Orforglipron Unpacked: The Next Era of Oral GLP-1 Agonists

Article by Dr. Donald Greig


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Following my Ozempic newsletter from two weeks ago, I’m thrilled to share news about an exciting new development in diabetes and weight management care from Eli Lily:


Orforglipron, a new oral GLP-1 receptor agonist that is currently under Phase III trial investigation and not yet available in Hong Kong or elsewhere. This newsletter will help you understand what Orforglipron is, how it compares to injectable GLP-1 receptor agonists like Ozempic (semaglutide) and Mounjaro (tirzepatide), and its potential advantages and disadvantages.


What Are GLP-1 Receptor Agonists?

GLP-1 receptor agonists are medications that mimic the hormone GLP-1 (glucagon-like peptide-1), which plays a key role in controlling blood sugar levels, appetite, and weight. These medications are commonly used to treat type 2 diabetes and, more recently, for weight management.

Current GLP-1 receptor agonists, such as Ozempic and Mounjaro, are administered via injection. Orforglipron, however, is the first oral GLP-1 receptor agonist under development, which could make this treatment more convenient for many patients.


Orforglipron: How Does It Work?

Orforglipron works similarly to injectable GLP-1 receptor agonists by:

  • Improving blood sugar control: Enhancing insulin release and lowering glucagon secretion.

  • Promoting weight loss: Reducing appetite and delaying gastric emptying.

  • Protecting cardiovascular health: Potentially lowering risks of heart disease.

The key difference is that Orforglipron is taken as a daily pill rather than requiring an injection.


Advantages of Orforglipron

  1. No Needles

    • One of the biggest advantages of Orforglipron is that it eliminates the need for injections. This makes it an attractive option for patients who are uncomfortable with needles or find injections inconvenient.

  2. Convenience

    • As an oral medication, Orforglipron may be easier to incorporate into daily routines compared to weekly injectable treatments.

  3. Potentially Similar Efficacy

    • Early clinical trials suggest that Orforglipron may offer comparable benefits in blood sugar control and weight loss to injectable GLP-1 receptor agonists.

  4. Accessibility

    • Oral medications are often more accessible and easier to store than injectables, as they don’t require refrigeration.


Disadvantages of Orforglipron

  1. Daily Dosing Requirement

    • Unlike injectables like Ozempic or Mounjaro, which are typically taken once weekly, Orforglipron must be taken daily. This may be less convenient for some patients who prefer the simplicity of weekly dosing.

  2. Potential for Gastrointestinal Side Effects

    • Similar to injectables, Orforglipron may cause side effects such as nausea, vomiting, diarrhea, or constipation. However, the daily oral dosing could lead to more frequent gastrointestinal discomfort, especially if not taken with food or as directed.

  3. Efficacy in Real-World Use

    • While early studies show promise, it remains to be seen whether Orforglipron’s efficacy in controlling blood sugar and promoting weight loss matches that of injectables in long-term, real-world settings.

  4. Absorption Variability

    • Oral medications can be affected by factors like food intake or stomach acidity, which might make the drug less predictable compared to injections that deliver medication directly into the bloodstream.

  5. Not Yet Available

    • As Orforglipron is still in the development phase, it is not currently available for prescription anywhere, including the UK or Hong Kong.


How Does Orforglipron Compare to Ozempic and Mounjaro?


Feature

Orforglipron (Oral)

Ozempic (Injection)

Mounjaro (Injection)

Administration

Daily pill

Weekly injection

Weekly injection

Needles

None

Yes

Yes

Convenience

High (no needles, but daily)

Moderate (weekly dosing)

Moderate (weekly dosing)

Efficacy

Promising but unconfirmed

Proven

Proven

Side Effects

GI symptoms possible

GI symptoms possible

GI symptoms possible

Refrigeration

None required

Required

Required

Key Takeaways

Orforglipron represents a promising new option for patients seeking an alternative to injectable GLP-1 receptor agonists. Its oral formulation offers a significant advantage for patients who prefer not to use needles, although the need for daily dosing and possible absorption variability may be considerations.

While Orforglipron is not yet available in the UK or Hong Kong, the future of diabetes and weight management care continues to evolve. If you are currently using a GLP-1 receptor agonist or are considering one, consult your healthcare provider to discuss the best treatment option for your needs.

Keep an eye out for more news as we find out more about this promising new medication!




Daily weight loss pill raises hopes for fighting obesity

Article by Poppy Koronka



While Mounjaro and Wegovy are injected, orforglipron is taken orally
While Mounjaro and Wegovy are injected, orforglipron is taken orally

A daily weight-loss pill is one step closer to being available in Britain as a new study has found that it can help people lose a “significant” amount of weight.

Almost one in five people taking orforglipron, which works in a similar way to Mounjaro or Wegovy, could lose 20 per cent of their body weight after taking the pill for eighteen months.


While Mounjaro and Wegovy are taken as an injection, orforglipron is taken as a once-daily tablet, which experts believe could help improve access to the popular weight loss drugs. Both Mounjaro and the new pill are manufactured by Eli Lilly, the American pharmaceutical giant.


The results were provisionally published in August, with the full paper detailing the findings published in the New England Journal of Medicine — bringing the drug one step closer to being available in the UK.



The pill is seen as a potential alternative to Wegovy, which is currently available only as an injection
The pill is seen as a potential alternative to Wegovy, which is currently available only as an injection

The study, which was also presented to the annual meeting of the European Association for the Study of Diabetes in Vienna, looked at 3,127 patients who took varying doses of orforglipron or a placebo. All of the patients were obese with a BMI of over 30, and all took the drug or a placebo for 72 weeks.


The team, led by Dr Sean Wharton from McMaster University in Canada, found that those taking the lowest 6mg dose of the tablet lost an average of 7.5 per cent of their body weight. Those taking the highest dose of 36mg on average lost 11.2 per cent of their body weight.


Among the patients on this dose, 54.6 per cent lost 10 per cent or more, 36 per cent lost 15 per cent or more and 18.4 per cent lost 20 per cent of their body weight or more during the trial.


The reductions in weight are not as dramatic as those seen in other GLP-1 agonist medications such as Mounjaro, with patients losing an average of 20.2 per cent of their body weight on the drug in similar trials.


In addition to weight loss, the researchers said that other health outcomes were improved by the medication, such as blood pressure, waist circumference and bad cholesterol. Patients on the trial did report some side effects, such as nausea, with experts considering them to be tolerable for most on the drug.

Wharton said: “This [medication] could mean an expansion of obesity interventions to groups who are currently excluded due to the cost of and lack of access to injectable medications.


“Where I think we’re going to see a difference in this medication, is the ability to have access to care around the entire world for those who previously did not have access to care.


“So I see this changing the way that we treat people living with obesity … what we don’t have is access to care for people who desperately need it.”


Write a patient newsletter on orforglipron, An oral form of the GLP 1 receptor agonists which is not yet available in either the UK or Hong Kong. Compare and contrast its advantages and disadvantages over the injectables such as Ozempic or Mounjaro


 
 
 

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