Orforglipron GLP-1 Pill: The Future of Weight Loss Treatments?

For years, the solution to obesity was always simple: “eat less and move more.”

That was until the introduction of GLP-1 weight loss treatments like Mounjaro, Wegovy, and Saxenda. With patients losing up to 20% of their initial body weight, these treatments have been life changing for those who’ve always struggled with their weight.

Building on the success of these injections, manufacturers are now turning their attention to the next frontier of weight loss treatments: oral GLP-1 pills. And at the forefront of this development is a drug called orforglipron.

So what could the arrival of orforglipron mean for the future of weight and obesity management?

In this article, we explain what orforglipron is and how it differs from current weight loss treatments. And explore how the oral pill might reshape obesity management in the years ahead.

What is Orforglipron?

Orforglipron is a once-daily oral pill currently in development for weight management and treating type-2 diabetes.

The manufacturer Eli Lilly (the same company behind the weight loss injection Mounjaro) expects orforglipron to be approved and available by early 2026. But there is currently no set release date.

Orforglipron belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists. Several GLP-1 receptor agonists are already available in the UK, including the weight loss injections Mounjaro, Saxenda and Wegovy.

Unlike GLP-1 injections, however, orforglipron belongs to a new class of “small-molecule, nonpeptide compounds.” This means it can be properly absorbed and used by the body in an oral form.

How Orforglipron Works

Like Mounjaro, Ozempic and Wegovy, orforglipron is a GLP-1 receptor agonist. 

GLP-1 agonists mimic the effect of GLP-1, a hormone your stomach releases when you eat food. This slows digestion, delays stomach emptying, and suppresses your appetite, which helps you lose and manage weight.

These treatments were originally designed to treat type-2 diabetes because they also help your body produce more insulin and regulate blood sugar.

Orforglipron works slightly differently to GLP-1 injections. The medication has a non-peptide structure, which provides the same effects as weight loss pens when swallowed. 

Injectable GLP-1 treatments, like Mounjaro and Wegovy, have a peptide-like structure. They’re made up of complex and large compounds that the acid and enzymes of the stomach would damage (similar to how the body breaks down food). The compounds are too big to pass the stomach wall, so they cannot be taken via the mouth (i.e. swallowed).

However, the new non-peptide compounds of orforglipron are smaller and more resilient. They won’t be destroyed by the stomach and can pass through the stomach’s wall. This allows you to take it orally, while still having the similar effects as other GLP-1s.

Orforglipron vs. GLP-1 Injections

While injections like Wegovy and Mounjaro have proven highly effective, they aren’t the most convenient choice for everyone. It’s widely assumed orforglipron, as a daily oral pill, will be a  “patient-friendly” alternative to GLP-1 jabs.

But how does Orforglipron compare to traditional GLP-1 injections? And is it really the more convenient option?

Is Orforglipron More “Patient-Friendly”?

Many people find pills easier to take and less intrusive than injections. Research has found patients often “preferred to avoid injectable medications in part due to embarrassment and inconvenience.”

Discretion is also important for patients. Unfortunately, both carrying excess weight and using GLP-1 medications for weight loss carry a stigma. Injections like Wegovy or Mounjaro require refrigeration before use, making them less discreet. Orforglipron is non-peptide, so “strictly maintaining a cold chain for storage and transport is not important.” This could make it easier to store away from friends, family or visitors.

And for individuals with a fear of needles, taking a daily oral pill is far less daunting.

Aamina Rafiq, Lead Pharmacist at Simple Online Pharmacy, agrees that a pill could be “easier for patients” who can find the injections hard to use, “especially at the beginning of their weight loss journey”.

“We get a lot of questions about how to use the injection,” she says. “Patients often ask where they should inject it. How to store the pens properly is a common concern too, especially when people travel. 

“A patient taking tablets instead of using injectables will likely have fewer concerns about how to use the medication. 

“There are also cases of misuse with the injections, whether intentional or not, like microdosing or stretching doses. A lot of these issues could potentially be avoided with an oral option.”

Pills Won’t Suit Every Patient

Still, not everyone will find orforglipron “patient friendly” because you need to take it every day. Some patients might find a weekly injection easier to incorporate into their routine – and easier to remember to take.

There is an oral GLP-1 weight loss pill currently available in the UK for type-2 diabetes: Rybelsus. And the pill, which contains semaglutide (the same active ingredient in Wegovy and Ozempic), comes with strict instructions. 

You have to take it on an empty stomach when you first wake up. You also have to wait 30 minutes before eating, drinking or taking other medications.

We don’t know the exact instructions for taking orforglipron. But if the directions are similar to Rybelsus, orforglipron might not suit every patient’s lifestyle.

Effectiveness

Phase-two trials found that obese and overweight patients taking orforglipron lost on average 14.7% body weight over 36 weeks. 

This is roughly the same amount of weight that patients on Mounjaro lose over the course of treatment. A separate 72-week trial found that obese or overweight patients using Mounjaro, the most effective weight loss injection available, lost between 15% and 20% of their body weight.

Side Effects

The phase-two trials for orforglipron found side effects were largely similar to those seen with GLP-1 weight loss injections.

Gastrointestinal side effects were the most commonly reported by patients taking orforglipron. This is the same as most GLP-1 jabs like Mounjaro common side effects include nausea, vomiting, constipation and diarrhea.

These were reportedly mild to moderate and usually occurred as they increased their dosage. Again, patients on GLP-1 injections report worsening side effects as they move up a dose.

However, we won’t know the full list of orforglipron side effects until the drug is licensed.

Orforglipron vs. Existing Weight Loss Pills

Orforglipron is not the only GLP-1 weight loss pills in development. According to Reuters, Novo Nordisk, the manufacturer behind Wegovy, is currently trialling a once-daily weight loss pill called amycretin. 

So it’s clear there’s a demand for an oral version of popular weight loss injections – and drugmakers are rushing to meet it.

But there are already oral weight loss pills available in the UK: Rybelsus, an oral GLP-1 (semaglutide) and Orlistat, which has a completely different mode of action. The popularity of these existing drugs – and barriers preventing wider uptake – can help shed some light on how orforglipron might change the weight loss treatment landscape.

Rybelsus

Rybelsus, an oral GLP-1 weight loss drug, was approved by the MHRA to treat type-2 diabetes in 2019. However, over the past couple of years, there has been a major global shortage of the oral GLP-1 drug.

This indicates a high demand for oral GLP-1s. And the availability of oral medication licensed for weight loss, like orforglipron, could help ease shortages.

Research also highlights concerns about oral semaglutide being “less effective for weight reduction than the approved dose of injectable semaglutide.” 

Therefore, there’s a “need for oral treatment options” with “weight-reduction efficacy similar to that of the approved and currently available injectable GLP-1 receptor agonists.” Promising phase-two trials suggest orforglipron could help meet this need.

Orlistat

Orlistat, licensed in 1998, was the first weight loss pill available in the UK.

It works very differently from GLP-1 medication. The capsules, which you take with each meal, prevent you from digesting about a third of the fat from food you eat. This undigested fat is passed out with your faeces.

The number of people taking orlistat has declined over the past decade, likely down to the emergence of more effective weight loss treatment. In 2010, approximately 1.28 million prescription items were dispensed in England, according to NHS England. By 2020, this had decreased to around 292,000.

However, it has remained a popular weight loss option among patients who find the drug simple and effective. As a once-daily oral pill, orforglipron might be an attractive option for patients that choose orlistat over GLP-1 jabs.

Is Orforglipron the Future of Weight Loss Treatments?

We won’t fully understand Orforglipron’s impact on weight loss and obesity management until it’s approved and widely used. Then we can assess uptake and look at some initial anecdotal evidence. It will also take some time for researchers to collect data and conduct clinical studies.

That said, it is likely that GLP-1 pills like Orforglipron will offer patients greater choice and flexibility. Some patients might find a once-daily pill less daunting and more discreet. Whereas others might prefer a once-weekly injection.

We’ve seen similar patterns in other medical areas, where patients can choose the forms of treatment that suit them best. For example, there are different methods of contraception, hair loss treatments and allergy treatments.

So orforglipron represents an exciting development in weight loss treatments. While its full potential remains to be seen, it’s clear that the future of weight loss is moving towards greater flexibility and choice for patients.

Key Takeaways

• Orforglipron is a Daily Oral GLP-1 Pill. It could offer a more discreet and “patient friendly” option for weight loss and management, compared to existing GLP-1 injections.

• Potential Pros of Orforglipron: Patients may find Orforglipron easier to use than injections, especially those with needle anxiety or concerns about storage and administration.

• Potential Cons of Orforglipron: Daily dosing might not fit into every patient’s schedule.

• Clinical Trials Show Orforglipron is Effective. Patients lost on average 14.7% of their body weight over 36 weeks.

• Side Effects Similar to GLP-1 Injections. Trials showed the main side effects were gastrointestinal issues like nausea and diarrhea. But the full safety profile won’t be known until it’s approved.

• Orforglipron Might Expand Weight Loss Treatment Options. It’s likely the drug will increase accessibility, remove barriers and lead to a rising number of patients using GLP-1s to lose and manage their weight.

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