Orforglipron: The First Oral GLP-1 Pill for Weight Loss and Diabetes

What is Orforglipron?

Orforglipron is a new type of GLP-1 receptor agonist that's currently going through clinical trials. It's not yet approved for use, but it's being tested as a new treatment for obesity and type 2 diabetes.

Made by the pharmaceutical company Eli Lilly, Orforglipron is different to other GLP-1 medications that are currently approved for weight loss as it doesn't need to be injected. The medication is a once daily oral nonpeptide, which means it's a tablet that's taken every day.

Orforglipron is currently undergoing phase 3 clinical trials and results look promising. If clinical trials continue to go well, Eli Lilly plans to apply for FDA approval in 2025/2026 for use in the US, and licensing in the UK should follow shortly after.

Mechanism of Action

Orforglipron works similarly to other GLP-1 receptor agonists by mimicking the hormone glucagon-like peptide-1. By acting like this natural hormone, Orforglipron works to slow down how quickly the stomach empties, decrease hunger cues in the brain, and improve insulin sensitivity. This is effective in weight management.

Benefits of GLP-1 Receptor Agonists

Together, these actions help to reduce feelings of hunger and make you feel fuller for longer, which can help you to eat fewer calories and lose weight. For people with type 2 diabetes, it can improve blood sugar regulation by increasing insulin secretion and sensitivity.

Like other GLP-1 agonists, there may be some added health benefits associated with taking Orforglipron. Studies suggest this medication may be able to reduce cardiovascular risk factors, leading to better cardiovascular outcomes and cardiovascular benefits in the long term.

What are the Benefits of Orforglipron for Weight Loss?

In clinical trials, Orforglipron has been shown to support weight loss in people who are overweight or obese. Between 46-75% of people taking Orforglipron for 36 weeks lost at least 10% of their starting bodyweight.

Participants also lost weight from around their middles, with an average 5.6 cm to 9.6 cm reduction in waist circumference at 36 weeks compared to their starting measurements.

Not only is Orforglipron effective for body weight reduction, it's also easy and convenient. Currently, the GLP-1 medications licensed for weight loss in the UK are all given as an injection. Orforglipron is an exception, as it can be taken as a daily oral pill. This is much easier than an injection, and requires less equipment like replacement needles and a sharps bins for discarded needles. It's also completely painless and quicker to administer.

Orforglipron is the first small molecule GLP-1 medication to complete a phase 3 trial, which means it's smaller than other GLP-1 receptor agonists and may be more easily absorbed.

How Effective is Orforglipron?

Orforglipron is currently in phase 3 clinical trials, and has completed phase 1 and 2 trials.

Results from phase 1 found that Orforglipron achieved significantly lowered HbA1c levels (a measure of what blood sugar levels have been over the last few months) and body weight compared to a placebo. Participants experienced a 1.5−1.8% reduction in HbA1c levels and 0.24−5.8 kg reduction in body weight after taking the medication for 12 weeks.

Phase 2 trials in people with type 2 diabetes and in individuals with obesity found similar results. In those taking diabetes medicines, Orforglipron was compared to treatment with another GLP-1 medication, dulaglutide, and a placebo. Patients who received 12mg of Orforglipron or more a day experienced significant reductions in HbA1c levels compared to people taking dulaglutide or the placebo.

In the phase 2 weight loss trial, patients receiving Orforglipron lost between 9.4−14.7% of their baseline body weight after 36 weeks compared to a loss of just 2.3% for people taking a placebo.

Phase 3 trials are ongoing, but the pharmaceutical company Eli Lilly has published some of the data on their website. Data from 559 participants taking the medication over a period of 40 weeks for diabetes shows an average HbA1c reduction of 1.3-1.6% compared to just 0.1% in the placebo set.

Although the current phase 3 trial is primarily measuring blood sugar level changes, it also looks at body weight changes. An average 4.7-7.9% body weight reduction was found in the group taking Orforglipron compared to just 1.6% in the placebo group. It was also noted that the weight loss had not plateaued when the trial was ended at 40 weeks, so participants could go on to lose more weight.

More research will give us additional information on how effective Orforglipron is for long-term weight and how it will reduce blood sugar levels. It will also be an effective option for weight management.

When Will Orforglipron Be Available in the UK?

Currently, Orforglipron is not approved in the UK or any other country as late-stage testing is still ongoing. The medication must be approved by the UK regulatory body, Medicines and Healthcare products Regulatory Agency (MHRA), to be licensed in the UK, and by the National Institute for Health and Care Excellence (NICE) for NHS use.

Eli Lilly plans to submit Orforglipron to the US Food and Drug Administration (FDA) by the end of 2025 for weight loss. It's expected that they will look to expand to the UK market after they gain approval. Based on this timeline, the medication may be available in the UK from 2026.

Quick Meds is following the approval process closely and plans to stock the medication as soon as it is approved for use in the UK.

Who is Orforglipron For?

As the medication isn't approved yet, the prescribing criteria has not yet been finalised. However, the criteria is likely to be similar to those of other GLP-1 medications taken for weight loss.

This means adults with a BMI (body mass index) ≥30, or BMI ≥27 with a weight-related health condition. Orforglipron will be a prescription medicine, so a clinical check with a prescriber will be needed before taking the medication to check it's safe for you.

Prescribing criteria will be different for people taking the medication for weight loss and for type 2 diabetes.

How is Orforglipron Taken?

Although information on prescribing and dosage is not yet available, we can see how Orforglipron has been administered to patients in the ongoing clinical trials.

Dosage and Administration

In clinical trials, Orforglipron is taken as a once-daily oral pill. Doses range from 12 mg to 36 mg, and doses as high as 45mg have been given in some trials. It's likely the dosing schedule will gradually be titrated up to allow the body time to get used to the medication and minimise side effects. This is how other GLP-1 medications are currently prescribed.

There are likely to be no food or water restrictions with taking Orforglipron, as studies suggest food doesn't impact how effectively the drug works.

Are There Any Side Effects?

Although a list of known side effects has not yet been published, like it would be with a licensed medication, we can see the side effects that patients have experienced during clinical trials. Most people who took the medication in clinical trials did not experience any side effects.

How Does Orforglipron Compare to Other Options?

Orforglipron seems to be similarly effective to other GLP-1 medications used for weight loss.

An average 70% of people taking the highest dose of Orforglipron for 36 weeks lost 10% or more of their starting bodyweight. Between 45-73% of people taking Wegovy and 63-94% of people taking Mounjaro lost at least 10% of their starting bodyweight. As studies assessing how well these medications work lasted more than 5 times longer than the one investigating Orforglipron, even more weight loss could be possible.

The main benefit of Orforglipron over other GLP-1 medications is that is comes as an oral tablet. Generally, patients find it easier, faster, and less painful to take a tablet than to give themselves an injection. This may mean people are better at taking it.

Lifestyle Tips to Maximise Your Weight Loss

As with any weight loss medication, it is important to make healthy lifestyle choices. This means eating a balanced diet that includes fewer calories than you were previously eating, and exercising regularly.

Why Buy Orforglipron from Quick Meds?

Orforglipron will be available to purchase from Quick Meds once it's approved for use as a weight loss medication in the UK.

Quick Meds is a UK online pharmacy that's registered with the Medicines and Healthcare products Regulatory Agency (MHRA) and General Pharmaceutical Council (GPhC). Our highly-trained team of prescribing pharmacists are there to guide you to the best treatment for you and answer any questions along the way.

Simply fill in the weight loss consultation and our team will review your medical history and prescribe the most suitable medication for your requirements. Medication is then shipped safely and securely to your door. We offer fast, discreet delivery across the UK.