Eli Lilly releases new safety data after FDA requested additional data to conduct extensive post-approval safety studies for Foundayo, including long-term monitoring of cardiovascular, liver, and thyroid cancer risks.
Following FDA’s recent
The request is seeking long-term data on potential liver injury, heart problems, and thyroid cancer risk, underscoring the agency's cautious approach to a drug built on a new active ingredient with a shorter safety track record than existing GLP-1 therapies.
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In the approval letter published Tuesday, FDA said the data available at the time of approval is not sufficient to fully characterize several potential risks associated with orforglipron.1 The agency requested Lilly to collect additional data on cardiovascular events including heart attack and stroke, drug-induced liver injury, and delayed stomach emptying, a condition in which food remains in the stomach longer than normal.
FDA also asked Lilly to gather at least 15 years of data on thyroid cancer risk, consistent with the boxed warning that existing injectable GLP-1 therapies such as Wegovy and Zepbound already carry.
The requests reflect the fact that orforglipron is a new active ingredient rather than an established molecule. By contrast, when the FDA
In the letter, FDA is also requiring Lilly to establish a registry tracking children with obesity who use weight loss drugs and a pregnancy registry to monitor outcomes in women who take Foundayo during pregnancy.1
A Lilly spokesperson said the post-approval requirements are routine. "Patient safety is Lilly's top priority and we actively monitor, evaluate, and report safety information for all our medicines," the spokesperson said in an emailed statement, describing the FDA's requests as consistent with the agency's standard approach to ongoing safety reviews of newly approved drugs.
Following the drugs approval and FDA's new request for safety requirements, Eli Lilly released positive topline results from Achieve-4, the largest and longest study of Foundayo in type 2 diabetes to date.2
The Phase III trial enrolled more than 2,700 participants across 15 countries and compared Foundayo against insulin glargine in adults with type 2 diabetes and obesity or overweight at increased cardiovascular risk.
In the trial, Foundayo met the primary endpoint by demonstrating non-inferior cardiovascular safety compared to insulin glargine, with a 16% lower observed risk of major adverse cardiovascular events.2 It also showed superior reductions in A1C and body weight, an 8.8% reduction in body weight versus a 1.7% increase with insulin glargine at 52 weeks. A pre-planned analysis found the risk of all-cause death was 57% lower with Foundayo, though that finding was not controlled for multiplicity.
"Achieve-4 adds a new dimension to that evidence, cardiovascular safety and a lower observed risk of all-cause death in patients who carry elevated cardiovascular risk," said Thomas Seck, M.D., senior vice president of product development at Lilly Cardiometabolic Health. "Together with the simplicity of a once-daily pill that requires no food or water restrictions, we believe Foundayo could be an important new treatment option for people with type 2 diabetes."
Lilly says it plans to submit Foundayo for a type 2 diabetes indication to the FDA by the end of the second quarter using a
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