Eli Lilly's once-daily pill Foundayo (orforglipron) was as safe for the heart as insulin glargine in the company's largest and longest study of the drug in type 2 diabetes, according to results released by Lilly on Sept. 30. The study, called ACHIEVE-4, was published in The Lancet and presented at the European Association for the Study of Diabetes meeting in Milan.
The trial also recorded fewer deaths among people taking the pill: 19, compared with 43 on insulin. Those death findings came from secondary analyses that were not designed to prove a benefit, and Foundayo is not yet approved by the FDA to treat type 2 diabetes.
For adults managing blood sugar, weight, and heart risk, the results address a practical question: Could a pill eventually replace a daily insulin shot without raising heart risk? The study shows the heart-safety bar was met. It does not show the pill saves lives.
A Heart Safety Test the Pill Passed
ACHIEVE-4 enrolled 2,749 adults with type 2 diabetes, overweight or obesity, and higher cardiovascular risk in 16 countries, including the United States. Most had established heart disease. Participants were randomly assigned to Foundayo or insulin glargine and followed for a median of about two years. Both patients and doctors knew which treatment was given, a design called open-label.
The trial was a noninferiority study. Its main goal was to show the pill was not meaningfully worse than insulin for major heart events, defined as heart-related death, heart attack, stroke, or hospitalization for unstable angina (sudden, worsening chest pain).
Those events occurred in 57 people on Foundayo (4.2%) and 67 on insulin (5.0%), according to EASD material in the Lancet paper. The hazard ratio was 0.84, with a 95% confidence interval of 0.59 to 1.20. Because the upper end of that range stayed below the preset safety limit of 1.8, noninferiority was met. Because the range also crossed 1.0, the trial did not prove the pill lowers heart risk.
Blood sugar and weight results were clearer. At 52 weeks, A1C fell 1.6 percentage points on Foundayo, compared with 1.0 on insulin, according to Lilly. Weight dropped 8.8% on the pill, while it rose 1.7% on insulin. By 104 weeks, 54.6% of pill users reached an A1C of 6.5% or lower, compared with 23.8% on insulin.
Fewer Deaths, with an Important Caveat
Deaths from any cause occurred in 1.4% of the pill group and 3.2% of the insulin group, a hazard ratio of 0.43. Heart-related deaths were also lower, with a hazard ratio of 0.47. Lilly notes that these analyses "were not controlled for family-wise type 1 error," which means the statistical safeguards against a chance finding were not applied.
That matters. An open-label design and many secondary comparisons both raise the odds that a striking number is partly luck. Lilly first shared topline results from ACHIEVE-4 in April. The Lancet paper adds peer review and detailed event counts.
Dr. Klara Klein, an assistant professor of medicine at the University of North Carolina School of Medicine, framed the results carefully. "For people living with type 2 diabetes, protecting the heart is as important as controlling blood sugar," she said in Lilly's release, adding that the trial "demonstrated an association with a lower risk of major cardiovascular events and death."
Dr. Thomas Seck, Lilly's senior vice president of product development for Lilly Cardiometabolic Health, said, "Foundayo has consistently delivered strong efficacy in type 2 diabetes across our Phase 3 ACHIEVE program." Eli Lilly sponsored the trial, which is registered as NCT05803421.
Side Effects, Price, and Who Can Get It
Stomach-related side effects were common. Nausea, vomiting, diarrhea, and related problems affected 62.1% of pill users, compared with 14.2% on insulin, and 10.6% of Foundayo users stopped treatment because of side effects during the first year.
The FDA approved Foundayo for chronic weight management on April 1, 2026. Its label warns that it may cause thyroid tumors, including cancer. Lilly lists self-pay prices starting at $149 a month for the lowest dose, and since July 1, Medicare Part D patients may pay $50 a month. Lilly has said it plans to seek FDA approval for type 2 diabetes, and no decision date has been announced.
A larger Lilly trial, ATTAIN-OUTCOMES, is testing the pill in adults with established heart or kidney disease. It is designed to provide the kind of proof of heart benefit that ACHIEVE-4 was never built to deliver. Until those results arrive, the lower death rate should be read as a promising signal rather than a reason to change treatment.
People most likely to be affected are adults with type 2 diabetes who also carry extra weight and heart risk. Anyone on insulin should not stop or switch without talking to a clinician, since changes in insulin can cause dangerous highs or lows in blood sugar.
Key Questions Answered
What did the ACHIEVE-4 trial show? Foundayo was not worse than insulin glargine for major heart events in adults with type 2 diabetes and higher heart risk, and it lowered A1C and weight more.
Does Foundayo lower the risk of death? Fewer deaths were seen on the pill, but that finding came from secondary analyses without full statistical controls. It is a signal, not proof.
Is Foundayo approved for type 2 diabetes? Not yet. It is FDA-approved for chronic weight management. Lilly has said it plans to seek approval for type 2 diabetes, and no decision date has been announced.
What are the main side effects? Nausea, vomiting, diarrhea, constipation, and reduced appetite were the most common. About 1 in 10 users stopped the drug because of side effects.
Who paid for the study? Eli Lilly sponsored the trial.
Should I switch from insulin to a pill? Only a clinician can judge that. Do not change diabetes medicines on your own.
Published by Medicaldaily.com
