Orforglipron, from the ACHIEVE and ATTAIN trials to Foundayo

Orforglipron is the first GLP-1 receptor agonist that is not a peptide. It is a small molecule, absorbed like an ordinary tablet, so it can be taken at any time with or without food. The FDA approved it as Foundayo on 1 April 2026 for chronic weight management in adults with obesity, or with overweight and at least one weight-related condition. It has also been submitted in the EU, Japan and Canada. The Foundayo guide covers how it is taken. This page covers the evidence.

One detail matters for reading the trials. They used capsule doses of 3, 6, 12 and 36 mg. The approved product is a tablet in different strengths, and the highest, 17.2 mg, is equivalent to the 36 mg capsule used in the trials.

ATTAIN-1: obesity without diabetes

The pivotal weight trial, published in the New England Journal of Medicine in 2025, randomised 3,127 adults with obesity and no diabetes to orforglipron 6, 12 or 36 mg or placebo for 72 weeks, alongside diet and activity advice. Under the treatment-regimen estimand, the trial's primary analysis, weight fell 7.5 percent on 6 mg, 8.4 percent on 12 mg and 11.2 percent on 36 mg, against 2.1 percent on placebo. On 36 mg, 54.6 percent lost at least 10 percent of body weight, 36.0 percent at least 15 percent and 18.4 percent at least 20 percent. Waist size, blood pressure, triglycerides and non-HDL cholesterol all improved. Between 5.3 and 10.3 percent stopped because of adverse events, against 2.7 percent on placebo. A figure of about 12 percent sometimes quoted for the top dose is the efficacy estimand, which assumes everyone stayed on treatment.

ATTAIN-2: obesity with type 2 diabetes

ATTAIN-2, in the Lancet, randomised 1,613 adults with type 2 diabetes and a BMI of 27 or more. At 72 weeks weight fell 5.1, 7.0 and 9.6 percent on 6, 12 and 36 mg against 2.5 percent on placebo, and HbA1c improved on every dose. As with all incretin drugs, weight loss in diabetes is smaller than without it.

ACHIEVE: type 2 diabetes and heart safety

ACHIEVE-1 was the first phase 3 result, in 559 adults with early type 2 diabetes managed by diet and exercise. Over 40 weeks HbA1c fell 1.24 to 1.48 percentage points across doses against 0.41 on placebo, to a mean of 6.5 to 6.7 percent, and weight fell up to 7.6 percent against 1.7 percent. There was no severe hypoglycaemia.

ACHIEVE-3 was the first head-to-head of two GLP-1 pills. In 1,698 adults with type 2 diabetes on metformin, orforglipron 12 and 36 mg lowered HbA1c more than oral semaglutide 7 and 14 mg over 52 weeks. From a baseline of 8.3 percent, HbA1c fell 1.91 points on orforglipron 36 mg, 0.44 points more than on semaglutide 14 mg. The trade-off was tolerability: 9 to 10 percent stopped orforglipron for adverse events against 4 to 5 percent on semaglutide, and pulse rose more on orforglipron. The trial was open label.

ACHIEVE-4 was the heart safety trial: 2,749 adults with type 2 diabetes and established cardiovascular or kidney disease, randomised to orforglipron or insulin glargine and followed for a median of two years. Major cardiovascular events occurred in 4.2 percent on orforglipron and 5.0 percent on glargine (HR 0.84, 95% CI 0.59 to 1.20), meeting the pre-set test for non-inferiority. It shows the pill does not raise cardiovascular risk compared with insulin. It was not built to show benefit, as SELECT did for injectable semaglutide and SOUL for oral semaglutide. Gastrointestinal events were reported by 62.1 percent on orforglipron against 14.2 percent on glargine, while significant low blood sugar was less common (6.8 against 19.2 percent).

ATTAIN-MAINTAIN: after an injectable

This phase 3b trial, in Nature Medicine in 2026, may matter most in practice. It took people who had lost weight on tirzepatide (205) or semaglutide (171) in the SURMOUNT-5 trial and switched them to orforglipron or placebo for a year. Among those whose weight had plateaued, people coming off tirzepatide kept an estimated 74.7 percent of their weight loss on orforglipron against 49.2 percent on placebo. Those coming off semaglutide kept 79.3 percent against 37.6 percent. The trial had no arm that simply stayed on the injection, so it cannot say whether switching is as good as continuing. The weight regain page covers what happens with no maintenance at all.

Where it sits

On average weight loss, orforglipron sits below injectable semaglutide 2.4 mg (about 15 percent in STEP 1) and tirzepatide (about 21 percent at 15 mg in SURMOUNT-1), though trials in different populations cannot be compared directly. Its case is practical: a daily tablet with no fasting, no water limit and no needle, a shorter half-life, and evidence as a maintenance step after an injection. The side effects are the GLP-1 class set: nausea, vomiting, diarrhoea and constipation, mostly during dose escalation. The label carries the same thyroid C-cell boxed warning as the injectables. For the other GLP-1 pill, see oral semaglutide trials.

Logging it

A daily pill lives or dies on the streak. Log each tablet, the step date on the 30-day ladder, weight and side effects, and labs if you have them, on one timeline. Peptide AI does that for Foundayo on the free tier; see the Foundayo tracker or the free GLP-1 tracker.