Foundayo Research Studies: What the Foundayo Studies Found – A Guide to the Orforglipron Trial Evidence

• Every major Foundayo (orforglipron) phase 3 trial explained, with verified published results
• Head-to-head results against oral semaglutide and dapagliflozin
• The switching study for people coming off Mounjaro or Wegovy injections
• Online consultation with UK-registered prescribers to discuss what the evidence means for you

When people search for "the Foundayo study", they usually mean the large phase 3 trials that led to its approval. There is no single study. Foundayo (orforglipron) was tested in two separate global trial programmes: ACHIEVE, in adults with type 2 diabetes, and ATTAIN, in adults living with obesity or overweight. Together they enrolled more than 10,000 people, and their results have been published in The New England Journal of Medicine, The Lancet, JAMA and Nature Medicine.

This guide explains what each trial tested, what it found, and how to read the results sensibly. That last part matters. Trial figures are averages from carefully selected groups, often reported in two different ways, and the dose numbers used in the trials do not match the numbers printed on UK packs. Understanding those points is the difference between realistic expectations and misleading headlines.

Key things to know

• Foundayo was tested in two phase 3 programmes: ACHIEVE (type 2 diabetes, more than 6,000 people) and ATTAIN (weight management, more than 4,700 people in the two main trials)
• In ATTAIN-1, people without diabetes on the highest dose lost an average of 12.4% of body weight over 72 weeks, versus 0.9% on placebo, among those who stayed on treatment
• In ACHIEVE-3, Foundayo lowered HbA1c and weight more than oral semaglutide in a head-to-head trial
• ATTAIN-MAINTAIN found people switching from tirzepatide or semaglutide injections kept most, but not all, of their weight loss
• The trials used different dose labels from UK packs: the highest trial dose of 36 mg corresponds to the 17.2 mg tablet
• Side effects were mainly digestive and similar to other GLP-1 medicines

How the Foundayo Trial Programme Is Structured

Eli Lilly ran the two programmes in parallel because it sought approval for two uses. ACHIEVE measured blood sugar control, using HbA1c (a measure of average blood sugar over about three months) as the main outcome. ATTAIN measured weight loss, using the percentage change in body weight as the main outcome.

This is why Foundayo's UK licence, granted by the Medicines and Healthcare products Regulatory Agency on 10 August 2026, covers both obesity treatment and type 2 diabetes in adults. The healthcare products regulatory agency approval also made the UK the first country in Europe to authorize Foundayo for chronic weight management. Each use rests on its own body of evidence.

The ATTAIN trial program, part of Eli Lilly's industry-sponsored clinical development program for Orforglipron, evaluated its safety and efficacy for weight management.

Placebo-controlled versus head-to-head trials

Some trials compared Foundayo with a placebo, a dummy tablet. These answer the question "does it work?". Others compared it directly with an existing treatment. These answer the more practical question "does it work better than what is already available?". Head-to-head trials are less common and especially useful for prescribers.

Blinded versus open-label trials

In double-blind trials, neither participants nor researchers know who is taking what, which reduces bias. In open-label trials, everyone knows. Head-to-head trials of medicines taken differently are often open-label, because disguising them is impractical. ACHIEVE-2 and ACHIEVE-3 were open-label. ATTAIN-1, ATTAIN-2 and ATTAIN-MAINTAIN were double-blind and placebo-controlled.

Why Trial Doses Differ From UK Pack Strengths

One source of confusion in Foundayo coverage is that the clinical trials and the UK product use different dose strengths.

The phase 3 trials reported orforglipron doses such as 3 mg, 6 mg, 12 mg, 24 mg and 36 mg using the study formulation. The UK commercial tablets use different strengths: 0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg and 17.2 mg.

These are not simply two different ways of printing the same milligram dose. The UK product information provides formulation-specific equivalences between the clinical-study hard capsules and the commercial tablets. For example, the 36 mg hard-capsule dose used in the clinical trials is equivalent to the 17.2 mg commercial film-coated tablet.

So a trial reporting a 36 mg dose does not mean that a patient taking the maximum UK 17.2 mg tablet is receiving less treatment. The UK prescribing schedule and commercial tablet strengths are the ones that apply to patients prescribed Foundayo in the UK.

The UK starting dose is 0.8 mg once daily, with increases after at least 30 days according to treatment response and tolerability. The maximum recommended dose is 17.2 mg once daily. Foundayo can be taken once daily at any time of day, without food or water restrictions.

Two Ways of Reporting Results: Why the Figures Vary

Many Foundayo figures come in two versions, which is why different articles quote different numbers for the same trial.

The efficacy estimand looks at people who kept taking the medicine as intended. It shows what the medicine does when taken consistently. The treatment-regimen estimand includes everyone who started, whether or not they stopped early or switched. It is closer to what happens across a whole population in real life. The efficacy figure is always the larger of the two. Neither is wrong, but a fair comparison between medicines has to use the same type of figure for both.

The ATTAIN Programme: Weight Management

ATTAIN-1: adults with obesity or overweight, without diabetes

ATTAIN-1 was a multicenter, randomized controlled trial that enrolled 3,127 adults without diabetes who had a BMI of 30 or above, or 27 to 30 with a weight-related condition. Participants took Foundayo at one of three doses or a placebo for 72 weeks, alongside a reduced calorie diet and increased physical activity. Results were published in The New England Journal of Medicine in September 2025.

All three doses led to significantly more weight loss than placebo, with ATTAIN-1 measuring percent body weight change over 72 weeks. On the highest dose, participants who stayed on treatment lost an average of 12.4% of their body weight, compared with 0.9% on placebo. Across reporting approaches, Foundayo’s average weight loss is also commonly summarised as around 11% over 72 weeks to support weight loss discussions. At that dose, more than half lost at least 10% of their body weight, showing meaningful weight loss, and some adults reached 20% or more; 39.6% lost at least 15%. In the more conservative analysis of everyone who started, adults on the highest Foundayo dose lost around 11% of body weight, and 54.6% on the highest dose lost at least 10%, compared with 12.9% on placebo.

Two further findings stand out. Among the 1,127 participants who had prediabetes at the start, up to 91% of those on Foundayo reached near-normal blood sugar levels, compared with 42% on placebo. And the highest dose reduced hsCRP, a blood marker of inflammation, by 47.7% in a pre-specified exploratory analysis. Blood pressure, triglycerides and non-HDL cholesterol also improved, with average reductions in waist circumference of 2.8 inches, triglycerides of 14.8%, and systolic blood pressure of 5.7 mmHg.

ATTAIN-2: adults with obesity or overweight and type 2 diabetes

People with type 2 diabetes usually lose less weight with any treatment than people without it. ATTAIN-2 enrolled 1,613 adults with obesity or overweight and type 2 diabetes, with HbA1c between 7% and 10%, across 136 sites in ten countries. Results were published in The Lancet in November 2025.

On the highest dose, participants who stayed on treatment lost an average of 10.5% of body weight at 72 weeks, compared with 2.2% on placebo. In the analysis of everyone who started, the figure was up to 9.6%. HbA1c fell by around 1.7 to 1.8 percentage points on the highest dose, and around two thirds of those participants reached an HbA1c of 6.5% or below.

ATTAIN-MAINTAIN: switching from injections to Foundayo

ATTAIN-MAINTAIN asked whether people who had already lost weight with injectable tirzepatide or semaglutide could maintain most of that loss after switching to once-daily oral orforglipron.

The trial included 376 adults from the SURMOUNT-5 programme: 205 who had previously received tirzepatide and 171 who had previously received semaglutide. Participants whose weight had reached a plateau were randomly assigned to orforglipron or placebo for 52 weeks in a double-blind design.

At week 52, the model-based treatment-regimen analysis estimated that participants switching from tirzepatide maintained 74.7% of their previous weight reduction with orforglipron, compared with 49.2% with placebo. Among those switching from semaglutide, the corresponding figures were 79.3% and 37.6%.

These percentages describe the proportion of previously achieved weight loss that was maintained; they do not mean that 74.7% or 79.3% of participants remained at exactly the same weight.

In sensitivity analyses, participants receiving orforglipron experienced an average weight increase of approximately 5 kg in the previous-tirzepatide cohort and approximately 1 kg in the previous-semaglutide cohort during the 52-week maintenance period. The study did not compare switching with simply continuing the injectable treatment, so it cannot establish that switching is equivalent to continuing tirzepatide or semaglutide.

The honest reading is that switching preserved most, but not all, of the earlier weight loss. People coming from tirzepatide regained around 5 kg on average over the year, and people coming from semaglutide around 1 kg. The researchers suggested the difference reflects tirzepatide's greater initial weight loss, which leaves more to regain. The trial studied a specific US population under trial conditions, and any change of treatment should be a decision made with your prescriber.

The ACHIEVE Programme: Type 2 Diabetes

The ACHIEVE programme enrolled more than 6,000 people with type 2 diabetes across several global regions. It also included head-to-head evidence: ACHIEVE-3 compared Orforglipron with oral semaglutide. The ACHIEVE programme also included head-to-head trials against established diabetes medicines, providing evidence on both glycaemic control and weight.

ACHIEVE-1: Foundayo on its own

ACHIEVE-1 enrolled 559 adults with type 2 diabetes managed by diet and exercise alone, and compared Foundayo with placebo over 40 weeks. Published in The New England Journal of Medicine in June 2025, it found HbA1c reductions of 1.3 to 1.6 percentage points across the doses tested, alongside weight loss.

ACHIEVE-2: head-to-head against dapagliflozin

ACHIEVE-2 compared three doses of Foundayo with dapagliflozin 10 mg, an SGLT2 inhibitor widely used in type 2 diabetes, in 962 adults already taking metformin. This 40-week open-label trial, published in The Lancet, showed Foundayo was at least as effective for HbA1c, and superior across the primary and key secondary endpoints, including weight, triglycerides, non-HDL cholesterol and systolic blood pressure.

ACHIEVE-3: head-to-head against oral semaglutide

ACHIEVE-3 was the first phase 3 trial to compare two oral GLP-1 medicines directly. It enrolled 1,698 adults with type 2 diabetes not adequately controlled on metformin, comparing two doses of Foundayo with two doses of oral semaglutide over 52 weeks. Published in The Lancet in February 2026, it found Foundayo delivered significantly greater improvements in HbA1c and weight across the primary and all key secondary endpoints. On the highest doses, HbA1c fell by about 2.2 percentage points with Foundayo compared with about 1.4 points with oral semaglutide 14 mg.

One practical difference matters here too. Oral semaglutide has to be taken on an empty stomach with a small amount of water, followed by a wait before eating. Foundayo can be taken at any time, with or without food.

ACHIEVE-5: added to insulin

ACHIEVE-5 tested Foundayo against placebo in people already using titrated insulin glargine, a long-acting insulin. Published in JAMA, it showed superior HbA1c reduction and weight loss when Foundayo was added. Combining a GLP-1 medicine with insulin does raise the chance of low blood sugar, which is why the UK leaflet says your prescriber may need to lower your insulin dose.

Key Results at a Glance

Cross-trial headline averages should be read cautiously, but commonly cited benchmarks for weight loss medicines include Wegovy at around 15% over 68 weeks and Mounjaro at up to 21% over 72 weeks, which may represent greater weight loss in separate study programmes.

What the Trials Showed About Side Effects

Across the programme, adverse events were consistent with other GLP-1 medicines, and gastrointestinal side effects were the most common adverse effects in trials. They were mainly digestive, with most side effects being mild to moderate gastrointestinal issues and other stomach-related symptoms, and were most common while the dose was being increased.

In ATTAIN-1, on the highest dose, nausea affected 33.7% of participants compared with 10.4% on placebo, constipation 25.4% versus 9.3%, diarrhoea 23.1% versus 9.6%, and vomiting 24.0% versus 3.5%. Around 10.3% of people on the highest dose stopped treatment because of side effects, compared with 2.7% on placebo. Across studies, roughly 5% to 10% of adults stopped Foundayo due to side effects. In the diabetes head-to-head trials, stopping rates due to side effects were also higher with Foundayo than with oral semaglutide or dapagliflozin.

One practical difference is that Foundayo is taken once daily by mouth, whereas Mounjaro and Wegovy are injectable medicines. A slow dose increase, as set out in the UK leaflet, exists to reduce these effects.The available phase 3 trials have not established a specific liver-safety concern, but longer-term safety monitoring and post-authorisation studies remain important as more people use orforglipron. Product information also carries a warning about thyroid C-cell tumours observed with GLP-1 receptor activity in animal studies. It is not known whether this risk applies to humans. Foundayo should not be used in people with a personal or family history of medullary thyroid carcinoma (MTC) or with MEN2.

How to Read These Results Sensibly

Averages are not predictions

Every figure above is an average. Some people lost much more weight and some lost little. Your own response depends on your starting weight, other health conditions, the dose you reach and tolerate, and the diet and activity changes you make alongside treatment.

Be careful with cross-trial comparisons

It is tempting to line up Foundayo's results against figures from trials of Mounjaro or Wegovy injections. Those trials used different populations, durations, doses and analysis methods, so direct comparisons can mislead.

Separate clinical trials of tirzepatide and semaglutide have generally reported greater average weight loss than the ATTAIN trials of orforglipron, but these medicines have not been compared directly with orforglipron in a weight-management head-to-head trial. Differences in participants, treatment duration, doses and statistical methods mean the percentages should not be treated as a direct ranking.

Trial conditions differ from everyday life

Trial participants receive regular check-ups, structured lifestyle advice and close follow-up. Outcomes in routine care can differ. This is one reason the treatment-regimen figures, which include people who stopped early, are worth knowing alongside the headline efficacy figures.

What Research Is Still Ongoing?

Foundayo's evidence base is still growing. Lilly has reported phase 3 studies of orforglipron in obstructive sleep apnoea, high blood pressure, knee osteoarthritis in adults with obesity and stress urinary incontinence, as well as longer-term cardiovascular and kidney outcome trials. Results from these will shape how Foundayo is used in future. The UK product information will be updated if new findings change its safety or licensed uses.

Talking to a Prescriber About the Evidence

A prescriber can help you understand how closely your circumstances match the populations studied, what outcomes were observed in those trials, and whether the treatment is appropriate for you. EverydayMeds offers an online clinical consultation with a UK-registered prescriber who can review your history and talk through the evidence with you. A qualified prescriber reviews your medical history, relevant medical conditions, and other medicines before starting treatment, and can explain the role of lifestyle changes, ongoing support, and the wider clinical team in safe treatment planning. Foundayo is currently available by private prescription, is not yet available on the NHS in the UK, and is being evaluated by the National Institute for Health and Care Excellence.