Orforglipron: The Oral GLP-1 Pill for Weight Loss

Orforglipron is a new glucagon-like peptide-1 (GLP-1) receptor agonist medication that has been approved in the US by the Food and Drug Administration (FDA) under the brand name Foundayo. It works similarly to Mounjaro and Wegovy by suppressing hunger and keeping you feeling fuller for longer. However, unlike these popular GLP-1 injections, orforglipron comes as a tablet that you swallow. This weight loss pill is manufactured by Eli Lilly.

Clinical trials have already shown that at its highest dose, orforglipron can result in an average 11.2% weight loss compared to 2.1% with a placebo after 72 weeks, making it a promising alternative to weight loss injections. In this guide, we explore orforglipron (Foundayo) in more detail, comparing it to other popular options, and discuss when it might be available in the UK.

Orforglipron works by mimicking the actions of the GLP-1 hormone, which naturally controls hunger, digestion, and blood glucose levels. By activating these receptors, orforglipron:

• reduces hunger
• increases feelings of fullness
• leads to decreased appetite and, therefore, calorie intake
• boosts insulin production
• lowers glucose (sugar) production in the liver

Together, these actions lead to weight loss and better-controlled blood sugar levels in type 2 diabetes.

Orforglipron is known as a GLP-1 receptor agonist and belongs to the same group of medications as the weight loss injections Mounjaro, Wegovy, and Nevolat. However, unlike these, which need to be injected either weekly or daily in the case of liraglutide (Nevolat), orforglipron is a daily tablet, which may be a more suitable route of administration for some people.

Although orforglipron has not yet been licensed for use in the UK or anywhere else, clinical trials are underway to assess its effectiveness and safety, which are required before a license can be requested. So far, the results are promising, and it’s currently in phase 3 of clinical trials.

Phase 3 trial results

Phase 3 clinical trials looking at the safety and effectiveness of oral orforglipron have found that at the highest dose, taking orforglipron for 72 weeks caused:

• an average weight loss of 11.2%
• reductions in cardiovascular risks, including waist circumference, low-density lipoprotein (LDL) cholesterol, triglycerides, and systolic blood pressure
• a weight reduction of at least 10% in 54.6% of people

Phase 2 trial results

Smaller phase 2 trials also demonstrated positive results for both obesity and type 2 diabetes.

Orforglipron for weight loss

A 26-week-long phase 2 trial involving obese adults or overweight adults with at least 1 weight-related condition (not diabetes), found that the average weight loss with orforglipron was between 8.6 and 12.6% compared to 2% with a placebo.

By week 36, up to 75% of people had lost at least 10% of their initial body weight compared to 9% given a placebo.

Orforglipron for type 2 diabetes

A 26-week phase 2 trial carried out in adults with type 2 diabetes found that the average reduction in blood sugar levels at the end of the trial was 2.1% with orforglipron compared to 0.43% with a placebo.

On average, participants in the trial also lost 10.1kg in body weight compared to 2.2kg with a placebo.

There are several potential benefits of taking GLP-1 pills, like orforglipron, compared to GLP-1 injections, like Wegovy and Mounjaro.

No self-injection required

Unlike medications like Mounjaro, Wegovy, and Nevolat, orforglipron is available as a daily pill and does not need to be injected. For anyone who would prefer not to inject themselves or has a fear of needles, GLP-1 pills could be a quicker, easier, and more convenient treatment option.

No food or water restrictions

Because orforglipron is a small molecule compound, it can be taken at any time of day, with or without food. Unlike some other GLP-1 medications, such as the Wegovy pill, it has no food, drink or timing restrictions, making it a more flexible option for some people.

Promising blood sugar stabilisation

Orforglipron looks promising as an effective type 2 diabetes treatment for people whose blood sugar levels have not been managed with insulin and lifestyle changes. Phase 3 trials show that even 6mg of daily orforglipron lowers blood glucose levels by 1.3% over 72 weeks compared to 1.8% at 36mg.

Effective weight management results

Orforglipron is showing promise in clinical research that it can effectively suppress hunger, contributing to weight loss. After 72 weeks of treatment, orforglipron helped up to 50.1% of people lose at least 10% of their starting body weight.

Clinical trial data specifically comparing orforglipron with other popular GLP-1 receptor agonists, like semaglutide (Wegovy) and tirzepatide (Mounjaro), is limited. However, using the available clinical research, we have found the following:

Side effects were reported in 86 to 90% of people given orforglipron in the weight loss clinical trial compared to 76% in the placebo group. In clinical trials, the most commonly reported side effects of orforglipron were:

• feeling sick
• constipation
• being sick
• diarrhoea
• burping

Side effects were more common in the 3mg starting dose compared to the 2mg starting dose, or if the dose was increased every 1 or 2 weeks compared to every 3 weeks. In the trial, 35 people stopped taking orforglipron because of side effects. Overall, the safety of orforglipron was similar to other GLP-1 receptor agonists.

Who cannot take orforglipron

Because clinical trials assessing the safety profile of orforglipron are still ongoing, it is not yet certain who it may or may not be suitable for. As the research continues, we will learn more about who can safely take orforglipron and who should avoid it.

However, it is likely that you will qualify for orforglipron if other GLP-1 medications are suitable for you. For example, if you have a body mass index (BMI) above 30, or 27 with weight-related conditions. Orforglipron is likely to be especially suitable for:

• anyone with a needle phobia or who would prefer to not inject themselves
• people looking for an alternative weight loss treatment
• anyone looking for a weight loss pill

It is not yet known when orforglipron may become available for weight loss in the UK, and it will need to be approved by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) first. It is currently only approved in the US under the brand name Foundayo. At the moment, there is no timeline for when it may undergo regulatory review and be licensed in the UK.

Even if orforglipron is approved by the MHRA, the National Institute for Health and Care Excellence (NICE) will need to decide if it can be prescribed on the NHS. Therefore, like other GLP-1 medications, orforglipron may be available with a private prescription before it is available on the NHS.