Home / Research / Foundayo (orforglipron) teardown

Study teardown · Foundayo (orforglipron) · EU recommendation October 15, 2026 · Labels and trials read · Sources checked October 16, 2026

Is the Foundayo (orforglipron) pill as good as Wegovy or Zepbound shots? Not for weight loss: about 11% versus 15% and 21%. But it’s the easiest GLP-1 to take, and with diabetes the gap mostly closes.

Not for weight loss. On each drug’s own US label, people on Foundayo’s top dose lost 11.1% of their body weight over 72 weeks. The figures for the others were 13.6% on the Wegovy pill, 14.9% on the Wegovy shot and 20.9% on Zepbound.[5][18][21] Foundayo’s advantages are practical. It’s one tablet a day, taken any time, with or without food.[5][3] In people with type 2 diabetes it matched the Wegovy shot’s weight loss almost exactly, in separate trials. More people quit it because of side effects than quit any of the others.[5][18][21]

Why this matters this week

On October 15, 2026, the European Medicines Agency’s drug committee (CHMP) recommended approving Foundayo across the EU, for weight management and for type 2 diabetes.[1][4] EMA called it a once-daily tablet “providing an alternative to injectable and other oral GLP-1 receptor agonists.”[3] The European Commission now has to sign off. EMA says that decision normally comes 67 days after the opinion, which would put it around December 21.[2] The US approved Foundayo for weight management on April 1, 2026, 50 days after Lilly filed. FDA called it the fastest approval of a new molecular entity since 2002.[6] Lilly says it has filed in more than 40 countries.[7] The Lancet’s October 17 issue carries Lilly’s heart-safety trial of the drug, with an editorial.[13][14] So millions of people are about to be offered a choice between a pill and a shot. Here is what the evidence says about that choice.

Why we say that

Comparing these drugs fairly takes some care, because companies headline different kinds of numbers. Lilly’s US launch release led with 12.4% weight loss for people on the top dose “who stayed on treatment,” versus 0.9% on placebo.[7] That figure is the efficacy estimand, an estimate of what happens if nobody stops the drug. Novo Nordisk does the same for the Wegovy pill: about 17% (16.6%) “if all patients stayed on treatment.”[19][20] The fairer number for a new patient counts everyone who was randomized, whether or not they stuck with the drug. That’s the number each US label prints in its main results table: 11.1% for Foundayo 17.2 mg, 13.6% for the Wegovy pill, 14.9% for the Wegovy shot and 20.9% for Zepbound 15 mg.[5][18][21] On the stay-on-drug count, the four come out at 12.4%, 16.6%, 16.9% and 22.5%. The ranking doesn’t change.[7][19][22][23]

Placebo groups also lost different amounts in each trial, so the cleanest comparison is the extra weight lost over placebo. Foundayo beat placebo by 9.0 percentage points, the Wegovy pill by 11.2, the Wegovy shot by 12.4 and Zepbound by 17.8.[5][18][21] These were separate trials lasting 64 to 72 weeks, so the comparison is rough. Still, Foundayo is the weakest of the four. A Novo-funded analysis that adjusted ATTAIN-1 and OASIS 4 for differences between their patients came to the same conclusion. It found the Wegovy pill ahead by about 3 points.[24] Take that with the same caution you’d apply to Lilly’s own numbers, because each company is grading its rival.

With type 2 diabetes, the gap mostly disappears

This is the part we haven’t seen discussed. People with type 2 diabetes lose less weight on every drug in this class. What differs is how much less, and Foundayo lost the least. In Lilly’s diabetes trial (ATTAIN-2), the top dose produced 9.6% weight loss versus 2.5% on placebo.[5][9] Wegovy’s diabetes trial (STEP 2) also produced exactly 9.6%, against 3.4% on placebo.[18] Zepbound produced 14.7% versus 3.2%.[21] In placebo-adjusted terms, Foundayo kept about 79% of its no-diabetes effect (7.1 of 9.0 points). Zepbound kept about 65% (11.6 of 17.8) and the Wegovy shot about 50% (6.2 of 12.4).[5][18][21] That is our arithmetic on numbers from separate trials, and none of these papers explains why the penalty varies. But if you have diabetes, the pill-versus-shot trade-off looks very different from the headlines.

Blood sugar is where Foundayo is strongest. In the only head-to-head trial against another GLP-1 pill (ACHIEVE-3, 1,698 people), Foundayo lowered HbA1c by 1.71 and 1.91 points on its two doses tested. Rybelsus, the diabetes version of oral semaglutide, lowered it by 1.23 and 1.47 points at 7 and 14 mg. Both Foundayo doses beat both semaglutide doses.[11] It also beat the SGLT2 pill dapagliflozin (−1.23 to −1.56 points versus −0.81).[12] EMA summarized the four diabetes trials as cutting HbA1c by about 1.2 to 1.9 points.[3]

The dose on the box isn’t the dose in the papers

If you read the trials and then look at a prescription, the numbers won’t match. ATTAIN-1 and ATTAIN-2 tested 6, 12 and 36 mg, and ACHIEVE-3 tested 12 and 36 mg.[8][9][11] Foundayo comes as 0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg tablets, on the US label and in the EU recommendation.[5][1] The trials used an earlier capsule formulation. Lilly ran a 429-person study showing the commercial tablets give the same blood levels at lower stated doses: 36 mg capsule equals 17.2 mg tablet, 12 mg equals 9 mg, 6 mg equals 5.5 mg, and so on down to 1 mg equals 0.8 mg.[10] The US label re-presents all the trial results under the tablet doses for this reason, and ACHIEVE-4 spells out “36 mg capsule [equivalent to 17·2 mg tablet].”[5][13] The label’s re-analysis gives 11.1% for the top-dose arm where the NEJM paper reported 11.2%, a rounding-level difference.[8][5] The practical point: 17.2 mg is the top dose, not a half dose.

What Foundayo gets right

The convenience is real. The Wegovy pill has to be taken on an empty stomach in the morning with no more than 4 ounces of plain water, followed by a 30-minute wait before eating, drinking or taking other pills.[18] Foundayo’s label just says to take it once daily, with or without food.[5] That’s possible because orforglipron isn’t a peptide. It’s a small, non-peptide molecule that switches on the GLP-1 receptor.[3] It was discovered by Chugai and licensed by Lilly in 2018.[7] The trial authors call it a “globally scalable” option.[17] In the US both pills start at the same self-pay price, $149 a month for the lowest dose. Novo lists $299 for the Wegovy pill’s top doses; Lilly lists $299 for Foundayo’s 9, 14.5 and 17.2 mg doses, with the top two held at that price only if you refill within 45 days.[7][19][25]

The weight loss, while smaller, is still meaningful. On the top dose, 54.5% of people without diabetes lost at least 10% of their weight and 35.9% lost at least 15%, versus 13% and 6% on placebo.[5] Waist size, blood pressure, triglycerides and non-HDL cholesterol all improved.[5][8] In ATTAIN-1, fewer people stopped Foundayo for any reason (22% to 24%) than stopped placebo (30%).[5] It may also work as a follow-on to the shots. In ATTAIN-MAINTAIN, people who switched from Zepbound to Foundayo kept 74.7% of their weight loss after a year, versus 49.2% on placebo. People switching from Wegovy kept 79.3% versus 37.6%. That trial didn’t test simply staying on the shots.[17]

The liver looks clean, and that’s worth noting because an earlier small-molecule GLP-1 failed on exactly this point. Pfizer dropped danuglipron in April 2025 after one trial participant had a possible drug-induced liver injury.[16] Lilly’s pooled analysis of seven orforglipron phase 3 trials, covering 11,220 people, found liver enzymes fell on average. It found no case that met Hy’s law, the standard warning sign of serious drug-caused liver injury.[15] That analysis was written mostly by Lilly employees. Independent post-marketing data will matter.

Side effects and safety

The side effects are the usual GLP-1 ones, and they’re common. In the pooled weight trials at 17.2 mg, 35% had nausea (10% on placebo), 25% diarrhea (11%), 24% constipation (9%) and 24% vomiting (4%). Gastrointestinal side effects of any kind hit 69% versus 37%. They were worst while the dose was being raised, and about 3% of people on orforglipron had severe ones versus 1% on placebo.[5] At the top dose, 10% stopped the drug because of side effects, versus 3% on placebo.[5] That 7-point excess is about double the gap for the Wegovy shot (6.8% versus 3.2%) or Zepbound 15 mg (6.7% versus 3.4%). The Wegovy pill’s gap was just 1 point (6.9% versus 5.9%), though its placebo group also quit more often (5.9%).[18][21] The one head-to-head pill trial points the same way. In ACHIEVE-3, people stopped Foundayo for side effects about twice as often as oral semaglutide (9% and 10% versus 4% and 5%).[11]

A few other signals are worth knowing about. Resting heart rate went up 4 to 5 beats per minute, versus 1 to 3 on Zepbound’s label. In ACHIEVE-3 the rise was 3.7 to 4.7 beats per minute, versus 1.0 to 1.5 on oral semaglutide.[5][21][11] Low blood pressure affected 2% versus 0.5% on placebo, rising to 4% in people already on blood-pressure drugs.[5] There were six confirmed cases of acute pancreatitis on orforglipron versus one placebo patient. Gallstones occurred in 1% versus 0.7%, and hair loss in 7% of women versus 3% on placebo.[5] Abnormal skin sensations (dysesthesia) showed up in 1% on 17.2 mg, a side effect also listed for Zepbound and Wegovy.[5][21][18] Like other GLP-1 drugs, Foundayo slows stomach emptying. The label says to switch from birth-control pills, or add a barrier method, for 30 days after starting and after each dose increase.[5]

The thyroid boxed warning has an unusual twist. Foundayo carries the same boxed warning about thyroid C-cell tumors as every GLP-1 drug, and it can’t be used by people with a personal or family history of medullary thyroid cancer or MEN 2.[5] But the label explains that orforglipron is “not pharmacologically active in rats or mice.” It caused no tumors in a two-year rat study, but that test couldn’t detect the receptor-driven effect behind the warning.[5] So the warning is inherited from the drug class. Rodent tests couldn’t confirm or rule out the risk for this molecule. The same blind spot applies to pregnancy. Animal studies were limited, and in one rabbit dose-finding study, malformations appeared in two fetuses at 14 times human exposure. The follow-up rabbit study, at up to about 6 times, found none.[5]

The catch with a small molecule: drug interactions

Peptide GLP-1s like semaglutide are broken down the way proteins are.[18] Orforglipron is cleared mainly by the liver enzyme CYP3A4, and that brings interactions most GLP-1 users have never had to think about.[5] The antibiotic clarithromycin raised orforglipron levels 3.5-fold, so the label caps Foundayo at 9 mg alongside strong CYP3A4 inhibitors. Inhibitors that also block a liver transporter, such as ritonavir, should be avoided entirely.[5] The seizure drug carbamazepine cut levels by 82%, so strong inducers should be avoided too.[5] The interaction also runs the other way. Foundayo roughly doubled the active form of simvastatin, so the label limits simvastatin to 20 mg a day.[5] If you take many medications, a pharmacist should check the list.

Heart protection, and the longevity question

The Wegovy shot and the Wegovy pill both carry a US indication for reducing heart attacks, strokes and cardiovascular deaths in people with established heart disease. Foundayo doesn’t, and neither does Zepbound.[18][5][21] Lilly’s heart trial, ACHIEVE-4, enrolled 2,749 people with type 2 diabetes and heart or kidney disease and compared Foundayo with insulin glargine for a median of 2 years. Major cardiovascular events occurred in 4.2% versus 5.0%, a hazard ratio of 0.84 (95% CI 0.59 to 1.20).[13] The trial was built to show the drug isn’t harmful. The bar was a confidence limit below 1.8, and it cleared that easily. It was not designed to show protection, and it didn’t: the interval includes no difference.[13][14] Deaths were 1.4% versus 3.2%, but that wasn’t the main endpoint, and the trial was open-label.[13] Lilly is also testing orforglipron in sleep apnea, high blood pressure, peripheral artery disease and knee osteoarthritis pain.[7] For anyone choosing a GLP-1 partly for long-term heart health, Wegovy is the only one of these four whose label claims a heart benefit.[18][21][5]

What the EU recommendation says, versus the US label

The EU recommendation is broader than the US label. EMA recommends Foundayo for weight management, explicitly “including weight loss and weight maintenance,” in adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition. It also recommends it for type 2 diabetes, either alone when metformin isn’t suitable or with other diabetes drugs.[1] The US label, revised in July 2026, covers weight management only.[5] EMA’s summary puts weight loss at “around 5% to 11%” depending on dose, versus about 2% to 2.5% on placebo. That’s the same everyone-counted range as the US label, not Lilly’s 12.4% headline.[3][5][7] The detailed EU prescribing information will be published only after the Commission decides, and each EU country will then set its own price and reimbursement.[1][3]

What a careful reader should notice

Every orforglipron trial cited here was funded by Lilly, and Lilly employees are co-authors on all of them. The heart trial and the head-to-head with oral semaglutide were open-label.[8][9][11][13][15] The weight trials were double-blind and large (3,127 and 1,613 people). At week 72, weight data were missing for 14% to 24% of people per arm in ATTAIN-1, and that gap was filled with statistical imputation.[5][8][9] The only direct pill-versus-pill weight analysis we found is an indirect one, paid for by Lilly’s main competitor.[24] No trial has put Foundayo up against the Wegovy pill, the Wegovy shot or Zepbound for weight loss.

The bottom line

Foundayo is a real, moderately strong GLP-1 that’s easier to take than any other. It works out to about 11% weight loss for a typical person offered it (about 12% for people who stay on it). On the same everyone-counted basis, the Wegovy pill gives about 14%, the Wegovy shot 15% and Zepbound 21%.[5][7][18][21] It looks strongest for people with type 2 diabetes. There it matched the Wegovy shot’s weight loss and beat Rybelsus on blood sugar.[5][18][11] The trade-offs are more people quitting over stomach side effects, a faster heart rate, drug interactions to check, and no proven heart benefit yet.[5][13] The choice between these drugs belongs with your prescriber. If you do start one, logging doses, step-ups and side effects in a tracker like Jabbit can make that conversation easier.

This page analyzes regulatory documents, prescribing information and published trials. It is not medical advice and does not recommend any medication or dose. Cross-trial comparisons are approximate. Charts were rebuilt by Jabbit from the label tables cited in each caption.