FDA approval letter for Foundayo sets liver, heart and stomach safety studies

Eli Lilly must gather additional safety data on its newly approved obesity pill Foundayo under the terms of the FDA letter that cleared the drug, agency documents posted April 14, 2026 show ^[1]. The approval letter, signed April 1, calls for postmarketing trials on liver injury, heart-related events and slowed stomach emptying, along with a lactation study ^[1][2].

Foundayo, whose molecule name is orforglipron, was authorized earlier in April under the Commissioner's National Priority voucher program, a pathway intended to speed decisions on medicines the agency views as critical to public health or national security ^[1]. Lilly began shipping the product the week before the letter became public ^[1]. Oral Wegovy, Novo Nordisk's semaglutide pill, reached the U.S. market in January, making Foundayo the second GLP-1 weight-loss pill launched in four months ^[1][2].

Most of the liver-related work centers on Achieve-4, an outcomes study in people with diabetes that is nearing completion ^[2]. Participants are being followed for heart attack, stroke, hospitalization for angina and cardiovascular death, with the pill compared against long-acting insulin ^[2]. Under the letter, Lilly must assess and statistically analyze unforeseen cases of elevated liver enzymes meeting particular safety criteria, liver damage, and withdrawals prompted by liver side effects ^[2]. Regulators also seek tallies of liver enzyme increases, any cases that meet a standard known as Hy's law — a cluster of biological markers suggesting the liver has been harmed — and instances where patients stopped treatment because of liver impairment ^[2]. The agency decided that observational studies, which have neither a placebo nor a comparator drug, would be adequate to establish whether liver risk rises ^[2]. The letter also requests information on "unexpected serious risk" of heart attacks and other cardiovascular problems ^[2].

For the digestive tract, one required study would use ultrasound to measure how an interruption in treatment and the duration of fasting change the amount of food retained in the stomach, addressing delayed gastric emptying associated with GLP-1 medicines ^[1]. Lilly is already running a separate trial comparing the pill with insulin glargine in people who have type 2 diabetes and obesity and are at higher cardiovascular risk ^[1]. On lactation, the agency asked for a milk-only study in women who have taken a dose, using a validated assay to measure drug concentrations in breast milk ^[1].

Lilly described the requests as "consistent with the agency's standard approach to ongoing safety evaluation of newly approved medicines" and said, "No hepatic safety signals have been observed for Foundayo across the Phase 3 program to date" ^[2]. Prescriber information the company publishes points to four Phase 3 diabetes trials and Phase 2 studies that found no greater risk of liver enzyme increases with the pill than with placebo or with semaglutide ^[2]. Lilly and the Department of Health and Human Services, the FDA's parent agency, did not immediately respond to requests for comment ^[1].

Jefferies analyst Michael Leuchten, who follows Novo Nordisk, speculated that regulators may have asked for the data because Foundayo was approved for obesity ahead of diabetes, unlike other GLP-1 drugs on the market, whose diabetes outcomes trials came first ^[2]. The letter's contents are absent from the Foundayo label, he noted, and he wrote that he does not expect the disclosure "to drive incremental demand for Novo's oral Wegovy" ^[2].

In studies, the Lilly pill cut body weight by 11% over 72 weeks, while oral Wegovy produced roughly a 14% reduction over 64 weeks ^[1]. Oral Wegovy is taken on an empty stomach with only a sip of water, 30 minutes before any other medicine, food or drink; Foundayo carries no such timing restrictions and can be taken whenever ^[1]. No trial directly comparing the two pills has been reported.

Why it matters for patients

Requirements attached to an approval are conditions a manufacturer must meet; they are not conclusions that a medicine has injured anyone. The FDA's requests do not appear on the Foundayo label, and Lilly reports no liver safety signals in its late-stage program so far ^[2]. The topics under study — liver damage, heart attacks and other cardiovascular events, and slower stomach emptying, a known effect of the GLP-1 class — are ones patients and their prescribers may discuss when choosing among treatments ^[1][2]. It has not been disclosed whether the agency will act on the findings, and no recall, withdrawal or added restriction on Foundayo has been reported ^[1].

What happens next

Achieve-4 was scheduled to conclude in April 2026, with a report due to the FDA in July ^[2]. Lilly has not disclosed timelines for the lactation study, the stomach-contents ultrasound study or the other requests ^[1].