Orforglipron - Oral GLP-1 Pill

The world of weight loss treatment is evolving fast. For years, the most effective options have required weekly injections. That is starting to change.

Novo Nordisk's oral Wegovy pill became the first approved oral GLP-1 for weight loss when it received FDA approval in December 2025, though it is not yet available in the UK. Eli Lilly is not far behind, with orforglipron, its own once-daily weight loss tablet, expected to follow later this year.

Orforglipron is not approved anywhere in the world yet, which means it cannot be prescribed. But from the trial results we have so far, it works well and is well tolerated by most people.

Here's what we know so far.

Key Takeaways

• A once-daily oral GLP-1 pill being developed by Eli Lilly
• In trials, people lost an average of 12.4% of their body weight over 72 weeks at the highest dose
• In a direct head-to-head trial, orforglipron outperformed oral semaglutide on both weight loss and blood sugar control
• Side effects are mostly mild to moderate gut symptoms, most common during the early weeks of treatment
• Submitted for approval in over 40 countries, with UK availability expected from late 2026

​​How does orforglipron work for weight loss?

Like Saxenda and Wegovy weight loss injections, orforglipron is a GLP-1 receptor agonist. It mimics a natural hormone called GLP-1, which helps reduce hunger, curb cravings, and promote fullness after eating.

Unlike Wegovy and Saxenda, which use peptide-based active ingredients, orforglipron is a non-peptide small molecule. This structural difference is what allows it to be taken orally. It also means it can be taken at any time of day without food or water restrictions, which is a meaningful practical advantage over oral semaglutide tablets, which require taking on an empty stomach and waiting at least 30 minutes before eating or drinking anything other than plain water.

FYI: Ozempic is a GLP-1 medication, too. It contains the same active ingredient as Wegovy (semaglutide) but is licensed for type 2 diabetes rather than weight loss.

How effective is orforglipron for weight loss?

Without type 2 diabetes

In a large clinical trial of over 3,000 adults with obesity, people taking orforglipron at the highest dose (36mg) lost an average of 12.4% of their starting body weight over 72 weeks, compared to 0.9% with placebo. Around 60% lost at least 10% of their body weight.

With type 2 diabetes

In people living with both obesity and type 2 diabetes, orforglipron at the highest dose led to an average weight loss of 10.5% over 72 weeks, compared to 2.2% with placebo. Around 50% lost at least 10% of their body weight.

Can orforglipron help with blood sugar control?

Yes, and the results are significant. In people with type 2 diabetes, 75% of those taking the highest dose reached an HbA1c of 6.5% or below, which is the level at which someone is no longer classed as diabetic. Blood sugar levels fell by an average of 1.3% to 1.8% across doses.

These findings were consistent with the ACHIEVE-1 trial, which also showed meaningful blood sugar reductions in adults with type 2 diabetes whose levels weren't well controlled on diet and exercise alone.

What are the other potential benefits of orforglipron?

Beyond weight loss, orforglipron has shown a range of other health improvements across trials. People taking the medication saw reductions in blood pressure, improvements in cholesterol, and lower triglyceride levels, a type of fat in the blood associated with heart and liver health.

A separate analysis also found that levels of a key inflammation marker fell by 50.6% at the highest dose. That is notable because chronic inflammation quietly contributes to a number of long-term conditions, including heart disease.

These findings suggest orforglipron may offer broader benefits for heart and metabolic health, but longer-term outcome trials are still ongoing.

What other oral GLP-1 medications are available?

Oral semaglutide is orforglipron's closest competitor. There are currently two oral semaglutide options: Rybelsus, licensed for type 2 diabetes (up to 14mg daily), and Wegovy tablets, approved in the US in December 2025 for weight loss at a higher 25mg dose. Wegovy tablets are not yet available in the UK.

People taking Wegovy tablets (25mg) lost 16.6% of their body weight over 64 weeks among those who completed the full course of treatment.

How does orforglipron compare to oral semaglutide?

The only head-to-head trial comparing the two is ACHIEVE-3, which compared orforglipron 12mg and 36mg against oral semaglutide 7mg and 14mg in 1,698 adults with type 2 diabetes over 52 weeks. Orforglipron 36mg outperformed semaglutide 14mg on every key measure:

• Weight loss: 9.2% with orforglipron vs 5.3% with semaglutide
• Blood sugar: 76.8% of people on orforglipron reached an HbA1c of 6.5% or below (no longer classed as diabetic) vs 50.9% on semaglutide
• Improvements in cholesterol, triglycerides and blood pressure also favoured orforglipron

Orforglipron also has a practical advantage: it can be taken at any time without food or water restrictions, whereas both Rybelsus and Wegovy tablets must be taken on an empty stomach, with a 30-minute wait before eating, drinking, or taking other medications.

It is worth keeping in mind that this trial used semaglutide at 14mg, the dose used for type 2 diabetes, not the higher 25mg dose that is licensed for weight loss. So we do not yet know how orforglipron would compare against oral Wegovy at its full dose. More people also stopped taking orforglipron due to side effects (around 9%) compared to semaglutide (around 5%), so tolerability is something to consider.

How does orforglipron compare to weight loss injections?

Orforglipron shows promising results, but current injectable GLP-1 medications do tend to produce greater weight loss at their highest doses. Wegovy at its highest dose (7.2mg) led to 20.7% weight loss over 72 weeks, while Mounjaro at its highest dose (15mg) produced up to 22.5% over the same period. Saxenda at its highest dose sits at the lower end, with around 7.4% after one year.

So while orforglipron (12.4% over 72 weeks) does not quite match the top-performing injectables, it is a step forward for people who prefer not to inject. For a detailed comparison with tirzepatide specifically, see our guide on orforglipron vs tirzepatide.

Tablets are also generally cheaper to manufacture than injectable medications, which could make orforglipron a more affordable option once it reaches the market.

How does orforglipron compare to orlistat?

Orlistat is currently the only weight loss tablet licensed in the UK. It works differently from GLP-1 medications, reducing the amount of fat your gut absorbs from food rather than suppressing appetite.

In terms of effectiveness, orforglipron appears significantly more effective. Around one in five people taking orlistat lose at least 10% of their body weight after a year, compared to around 60% of people on orforglipron 36mg achieving the same over 72 weeks.

Can orforglipron help maintain weight loss after stopping injections?

Many people who have reached their goal weight on Wegovy or Mounjaro are now asking what comes next, and whether switching to a tablet could help them maintain their results.

The ATTAIN-MAINTAIN trial followed people who had already lost weight on Wegovy or Zepbound over 72 weeks before switching to orforglipron. Those switching from Wegovy had lost around 18kg on their injections and gained back less than 1kg after switching. Those switching from Zepbound had lost around 25kg and gained back 5kg.

In both cases, the vast majority of weight lost was maintained. Full results are still to be published, but this is promising early evidence for orforglipron as a maintenance option.

Orforglipron side effects: what we know so far

Orforglipron side effects were mostly mild to moderate and consistent with other GLP-1 medications. The most commonly reported in trials were:

• Nausea (affecting 29-36% of people)
• Constipation (22-30%)
• Diarrhoea (21-23%)
• Vomiting (13-24%)

These were most common during dose escalation and generally eased over time. Early data also suggests orforglipron may cause fewer gut-related side effects than Mounjaro, which works on two hormones (GLP-1 and GIP) rather than one. That dual action is what makes Mounjaro particularly effective for weight loss, but it may also contribute to more side effects.

When will orforglipron be available in the UK?

Eli Lilly, the manufacturer of orforglipron, has submitted it for approval in over 40 countries, with a US decision expected between April and June 2026.

For the UK, it first needs approval from the MHRA (Medicines and Healthcare products Regulatory Agency). Once that is granted, private clinics can prescribe it straight away. NHS availability requires a further assessment by NICE (National Institute for Health and Care Excellence), which typically takes longer. Based on current timelines, orforglipron is most likely to reach the UK via private prescription from late 2026 onwards.

Side effects support at Voy

"If you're using Voy and you experience any side effects, rest assured that our expert clinicians are just a message or phone call away. They can adjust your dose, prescribe medication to ease your symptoms, or simply offer reassurance.

Everyone responds differently to weight loss treatment and we'll help you find what feels right for you."

Phoebe Fox - Weight Loss Specialist

Start your weight loss journey today

Orforglipron is exciting, and we will be keeping a close eye on it as it moves through the approval process. But if you are ready to start now, you do not have to wait.

Wegovy and Mounjaro are available today, backed by years of clinical evidence, and have already helped hundreds of thousands of people across the UK lose weight. Through our programme, we can post your medication to you each month, with support from our clinical team every step of the way.

Take our short quiz to see if you are eligible.