Foundayo (orforglipron) is FDA-approved for weight management, not as a heart medicine. In ACHIEVE-4, Lilly reported that Foundayo was no worse than insulin glargine for major heart events in adults with type 2 diabetes at higher heart risk. That tells you Foundayo stayed inside a preset safety margin. It does not tell you Foundayo protects your heart.
| What it is approved for | With a reduced-calorie diet and more activity, to reduce excess body weight and keep it off in adults with obesity, or overweight plus at least one weight-related condition. The FDA approved it on April 1, 2026. It is not approved to treat type 2 diabetes. |
| ACHIEVE-4 (Lilly, Sept 30, 2026) | Open-label Phase 3 trial of 2,749 adults with type 2 diabetes and overweight or obesity at increased heart risk. Foundayo was compared with insulin glargine, not placebo. |
| Main heart result | MACE-4 hazard ratio 0.84 (95% CI 0.59 to 1.20; p = 0.336). It met the noninferiority limit (upper bound below 1.8). That is a safety-margin result, not proof of benefit. |
| Death analyses | Lower cardiovascular-death and all-cause-death figures were not controlled for family-wise type 1 error. Treat them as exploratory. |
| Heart rate (label trials) | Pulse rose about 4 to 5 beats per minute on average. Tachycardia was reported in 3% on Foundayo vs 0.9% on placebo. |
| Cost | Medicare's GLP-1 Bridge lists a $50 copay for eligible drugs from July 1, 2026. Ask your pharmacy or insurer about Foundayo's price (see the cost section). |
What did ACHIEVE-4 find about heart events?
Lilly announced the detailed results on September 30, 2026. It says they were presented at the European Association for the Study of Diabetes meeting and published in The Lancet. Lilly's release is the manufacturer's own account. It reports the following, with Foundayo compared against insulin glargine.
| Measure | Result reported by Lilly | What it means for you |
|---|---|---|
| MACE-4 (cardiovascular death, heart attack, stroke, or hospitalization for unstable angina) | HR 0.84; 95% CI 0.59 to 1.20; p = 0.336 | Primary endpoint. It met the noninferiority limit. The range includes 1, so it shows no difference either way. |
| MACE-3 (cardiovascular death, heart attack, stroke) | HR 0.77; 95% CI 0.52 to 1.13; p = 0.181 | Key secondary endpoint. The range also includes 1. |
| Cardiovascular death | HR 0.47; 95% CI 0.25 to 0.90 | Pre-planned but not controlled for family-wise type 1 error. Exploratory. |
| All-cause death | HR 0.43; 95% CI 0.25 to 0.75 | Same limit. Exploratory. |
| Stopped treatment because of side effects | 10.6% on Foundayo during the 52-week minimum treatment period | Lilly gave no matching figure for insulin glargine in this release. |
Lilly also reported, at week 52, an A1C change of -1.6% vs -1.0% and a body weight change of -8.8% vs +1.7%. It reported smaller rises or bigger drops in several heart-risk markers: waist circumference down 7.0 cm, systolic blood pressure down 4.4 mmHg, triglycerides down 18.9%, non-HDL cholesterol down 6.6% and hsCRP down 38.9%. It also reported a slower decline in kidney function. Lilly marked waist, lipid, blood pressure, hsCRP and kidney results as not controlled for family-wise type 1 error.
Does this mean Foundayo protects your heart?
No. Several limits matter for your decision.
- Noninferiority is a ceiling test. It asks whether heart-event risk stayed under a preset margin (hazard ratio below 1.8). The range of 0.59 to 1.20 is wide. It fits a lower risk and a modestly higher one.
- The MACE-4 and MACE-3 figures below 1 were not statistically significant. Do not quote them as a proven 16% or 23% reduction. If you want a plain-language guide to why that matters, see this explainer on p-values and statistical significance.
- The death analyses were outside the controlled testing order. Lilly says they suggest more comprehensive health benefits. That is the sponsor's reading. Analyses like these generate ideas but cannot confirm benefit.
- The trial was open-label. Participants and doctors knew who got which treatment. The comparator was insulin glargine, not placebo.
- The people studied had type 2 diabetes. Foundayo's approved use is weight management, so the results do not map neatly onto everyone who might be prescribed it.
- Foundayo's label has no heart-risk-reduction indication. The Wegovy prescribing information does list reducing major cardiovascular events in adults with established heart disease and obesity or overweight, for both the tablet and the injection. Lilly says its ongoing ATTAIN-OUTCOMES trial is studying cardiovascular outcomes in adults with established cardiovascular or kidney disease.
For a wider look at what GLP-1 drugs have shown for the heart, read our page on GLP-1 medications and heart health.
Has the FDA raised a heart or liver concern about Foundayo?
The FDA's approval letter required Lilly to complete ACHIEVE-4. It asked for a report with adjudicated heart events and an assessment of possible drug-induced liver injury, including Hy's Law plots, liver enzyme tables and case reports. The letter says only a clinical trial would be enough to assess an unexpected serious risk for major adverse cardiovascular events and drug-induced liver injury. That is a standard postmarketing requirement. It is not a report that Foundayo caused heart or liver harm. The letter's schedule listed trial completion for April 2026 and a final report for July 2026.
Lilly's September 30 release does not report liver results. When you talk to your prescriber, ask whether the FDA has reviewed the final report. Our FDA requirement explainer walks through the letter.
What does Foundayo do to heart rate and blood pressure?
The FDA-approved prescribing information reports these effects from the two weight-management trials.
| Measure | What the label reports |
|---|---|
| Pulse | Mean rise of 4 to 5 beats per minute from baseline, vs 0.5 with placebo. At week 72 the rise was 3.6 to 4.6 bpm in Trial 1 and 2.8 to 3.9 bpm in Trial 2, depending on dose. |
| Tachycardia | 3% on Foundayo vs 0.9% on placebo |
| Low blood pressure (hypotension) | 2% on Foundayo vs 0.5% on placebo. It was 4% in people also on blood pressure medicine and 1% in those not. |
| Systolic blood pressure | Fell about 4 to 6 mmHg at week 72 in Trial 1, with smaller differences from placebo. The label notes these differences were not controlled for multiplicity. |
| QTc interval (heart rhythm timing) | No clinically significant prolongation at 1.4 times the peak level from the top dose |
If you notice palpitations or a racing heartbeat, tell your prescriber, especially if you have a rhythm condition.
Heart medicines that interact with Foundayo
The label says not to exceed simvastatin 20 mg daily with Foundayo, because exposure to the active simvastatin metabolite roughly doubled. Strong CYP3A4 inhibitors cap the Foundayo dose at 9 mg. Verapamil, a moderate inhibitor, raised orforglipron exposure about 2-fold in modeling. Foundayo also slows stomach emptying, which can change how other pills are absorbed. Do not change any medicine on your own. Bring your full list to your cardiologist, and use our cardiologist question guide to prepare.
Is Foundayo safe to take?
It is an FDA-approved prescription drug with real warnings, and whether it is safe for you depends on your history. In the two placebo-controlled weight trials, 8% of people on Foundayo stopped because of side effects, vs 3% on placebo. Most stopped for stomach reasons. The label's main warnings:
- Boxed warning: risk of thyroid C-cell tumors. Do not use Foundayo with a personal or family history of medullary thyroid carcinoma or with MEN 2. Orforglipron was not active in rodents and did not produce tumors there. The label says human relevance has not been determined.
- Pancreatitis, severe stomach reactions, acute kidney injury from dehydration, low blood sugar (higher risk with insulin or sulfonylureas), serious allergic reactions, gallbladder disease, worsening diabetic retinopathy in people with type 2 diabetes, and aspiration during anesthesia or deep sedation. Tell your care team before any planned surgery or procedure.
- Pregnancy: it may cause fetal harm, and the label says to stop it when pregnancy is recognized. Birth control pills may work less well. The label advises a non-oral or barrier method for 30 days after starting and after each dose increase.
- Do not combine it with another GLP-1 receptor agonist.
You can report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch, or to Lilly at 1-800-545-5979.
What are the side effects of Foundayo?
These are the label's reactions reported in 5% or more of people, from the pooled placebo-controlled trials.
| Side effect | Placebo | 5.5 mg | 9 mg | 17.2 mg |
|---|---|---|---|---|
| Nausea | 10% | 26% | 34% | 35% |
| Constipation | 9% | 20% | 27% | 24% |
| Diarrhea | 11% | 21% | 23% | 25% |
| Vomiting | 4% | 13% | 21% | 24% |
| Dyspepsia | 4% | 12% | 16% | 13% |
| Abdominal pain | 7% | 13% | 14% | 14% |
| Headache | 7% | 8% | 9% | 9% |
| Fatigue | 4% | 6% | 7% | 9% |
| Hair loss | 2% | 4% | 4% | 5% |
The label also lists abdominal distension, belching, reflux and gas at 5% or more. Nausea, vomiting and diarrhea were highest while the dose was being raised and eased over time. Hair loss was reported more in women (7%) than men (0.9%) and was linked to weight loss. Across both trials, 10% of people on 17.2 mg stopped because of side effects.
How do the side effects compare with Zepbound?
Lilly's safety summaries for the two drugs share a boxed thyroid tumor warning. Both list nausea, vomiting, diarrhea, constipation, abdominal pain, fatigue, belching, hair loss and heartburn or indigestion among common effects. Zepbound also lists injection site reactions and allergic reactions, since it is a weekly injection. Foundayo is a daily tablet. The Foundayo label says rates from different trials cannot be directly compared, so you cannot rank the two from these lists. For the injectable drugs, see semaglutide vs tirzepatide.
Can Foundayo cause liver failure?
Liver failure is not among the label's listed warnings and precautions. The FDA did ask Lilly to assess possible drug-induced liver injury from ACHIEVE-4, as described above. That is a required check for unexpected risk, not a finding of injury.
The label says Foundayo is not recommended in severe liver impairment (Child-Pugh Class C), where drug exposure was 4.6 times higher. No dose change is recommended for mild or moderate impairment. If you have liver disease, tell your prescriber before you start. If you notice yellow skin or eyes, call your clinician. Yellowing can also signal gallbladder problems, which the label does list.
Is Foundayo a GLP-1, a semaglutide or a tirzepatide?
Foundayo is a GLP-1 receptor agonist in tablet form. It is not semaglutide (the ingredient in Wegovy and Rybelsus) and not tirzepatide (the ingredient in Zepbound). Lilly describes it as a small-molecule, non-peptide oral GLP-1. The FDA says it does not need to be taken on an empty stomach.
What is Foundayo for?
The only FDA-approved use is weight management in adults with obesity, or overweight plus at least one weight-related condition, alongside a reduced-calorie diet and more physical activity. Lilly says it is studying Foundayo for type 2 diabetes and other conditions, and said in June it planned to submit for type 2 diabetes. Until the FDA approves that use, it is not a diabetes drug.
How does Foundayo compare with oral semaglutide?
Two manufacturers have each published an indirect comparison, and they disagree.
- Lilly (Sept 29, 2026): In adults with type 2 diabetes, an Lilly analysis of ACHIEVE-3 and PIONEER PLUS reported 1.5% more weight loss and 0.3% more A1C reduction with Foundayo 17.2 mg than oral semaglutide 25 mg at 52 weeks. The figures assume everyone stayed on treatment. Lilly's own executive said head-to-head trials give the best comparison and that Foundayo may deliver weight and A1C lowering similar to oral semaglutide 25 mg.
- Novo Nordisk (April 2, 2026): In adults without diabetes, Novo's analysis reported 3.2 percentage points more weight loss with oral semaglutide 25 mg than orforglipron 36 mg, which Novo says equals the approved 17.2 mg tablet. It also reported higher odds of stopping for side effects with orforglipron, and cautioned that adverse event counts were low.
Neither analysis looked at heart events, and neither is a head-to-head trial. Lilly's footnote says a 25 mg daily dose of oral semaglutide is not approved in the U.S. for type 2 diabetes. One practical difference is dosing: the Wegovy tablet label says to take it on an empty stomach in the morning with water and wait 30 minutes before eating, while Foundayo can be taken with or without food.
When is the best time of day to take Foundayo?
The label says to take one tablet once daily, with or without food, and sets no time of day. Pick a time you can keep. Swallow it whole and never take more than one tablet a day. If you miss a dose, take it as soon as you can and do not double up. If you miss 7 or more doses in a row, the label says to restart the dose climb at a lower dose, so call your prescriber.
| Step | Daily dose |
|---|---|
| Start | 0.8 mg |
| After at least 30 days | 2.5 mg |
| After at least 30 more days | 5.5 mg |
| Optional steps, at least 30 days apart | 9 mg, 14.5 mg, then 17.2 mg (maximum) |
How much weight can you lose in a month on Foundayo?
The label reports no one-month figure. You start at 0.8 mg and the dose steps up no faster than every 30 days, so the first weeks are on low doses. Ask your prescriber what to expect on your schedule. The label's results are at 72 weeks.
| At week 72, average weight change | Placebo | 5.5 mg | 9 mg | 17.2 mg |
|---|---|---|---|---|
| Trial 1, no diabetes | -2.1% | -7.4% | -8.3% | -11.1% |
| Trial 2, type 2 diabetes | -2.5% | -5.1% | -7.0% | -9.6% |
These are group averages. Your result may differ.
Does Foundayo cause muscle loss?
The label says Foundayo reduces body weight with greater fat mass loss than lean mass loss. It lists no muscle-specific warning. If you are concerned, ask your clinician how to keep your strength up during weight loss.
How much does Foundayo cost?
Lilly's releases do not state a price, and cost depends on your coverage. For Medicare Part D members, CMS runs a short-term Medicare GLP-1 Bridge from July 1, 2026 through December 31, 2027. It lists a $50 copay for eligible drugs. The Part D deductible does not apply, and the copay does not count toward your out-of-pocket costs. CMS says the program covers certain GLP-1 drugs and does not name Foundayo on that page, so check Medicare.gov/glp1bridge or call 1-800-MEDICARE (1-800-633-4227). For everyone else, ask your pharmacy and insurer, or contact Lilly at 1-800-545-5979 or foundayo.lilly.com. Prices and coverage change.
What do reviews and complaints say?
The most reliable picture of how people tolerate Foundayo is the trial data above: mostly stomach side effects, worst during dose increases, with 8% stopping in the weight trials. For your own experience, report problems to the FDA or Lilly at the numbers above. Our Foundayo label review goes through the label in more detail.
Before you start Foundayo
- Ask your prescriber whether you have thyroid cancer in your family, pancreas, gallbladder, kidney or liver problems, or diabetic eye disease.
- Bring your full medicine list, especially simvastatin, verapamil, insulin or sulfonylureas, and oral birth control.
- Tell your cardiologist if you have a rhythm condition or take blood pressure medicine, since Foundayo raised pulse and lowered blood pressure in trials.
- Ask whether the FDA has reviewed the final ACHIEVE-4 report, and whether your coverage includes Foundayo.
- Tell every clinician before surgery or sedation that you take it.
This page is general education, not medical advice. Do not start, stop or change a medicine without a licensed clinician.
By UTCardiothoracicSurgery.com Editorial Team