Eli Lilly is wasting no time in pursuit of the next indication for its newly christened obesity pill Foundayo, presenting new data in diabetes Thursday that also serve to address the FDA’s desire for more safety info on the oral GLP-1.
The results seen with Foundayo, also known as orforglipron, enabled Lilly’s late-stage Achieve-4 study to hit its primary endpoint. Specifically, the drug demonstrated non-inferiority to insulin glargine in adults with Type 2 diabetes and obesity, or who are overweight, who are at increased cardiovascular risk.
The risk of major adverse cardiovascular events (MACE)—including cardiovascular death, heart attack, stroke or hospitalization for unstable and sudden chest paint—was 16% lower in the trial’s Foundayo cohort compared to the insulin arm, Lilly said in an April 16 press release.
Meanwhile, Foundayo also proved superior to insulin glargine at improving blood sugar levels and helping patients reduce body weight at the one-year mark, with those benefits persisting through 104 weeks of treatment, according to Lilly.
With safety and efficacy successes in hand, the company says it will now submit the drug to the FDA for an approval verdict Type 2 diabetes by the end of the second quarter, with plans to once again leverage the new Commissioner’s National Priority Review Voucher program.
That lower MACE risk for Foundayo, which was the study’s prime non-inferiority goal, may help appease the FDA’s desire for additional safety information on the drug, as laid out in the approval letter (PDF) for Foundayo issued at the top of the month, when it was greenlit in obesity.
In that letter, the regulator called on Lilly specifically to accrue more data on the med’s potential link to MACE and drug-induced liver injury, plus further information about delayed gastric emptying associated with Foundayo, as well as its potential effects in lactating women.
The agency singled out the Achieve-4 study as an appropriate vehicle to furnish the necessary MACE data.
Lilly noted that while its trial didn’t control for multiplicity, the risk of all-cause death was “significantly lower” for patients on Foundayo versus insulin glargine, too. Moreover, the company said its study included a “thorough analysis of potential drug-induced liver injury,” with its analyses confirming “no hepatic safety signal, consistent with all prior studies in the ACHIEVE and ATTAIN programs.”
Lilly boasted that Achieve-4 marks its “largest and longest study” of Foundayo for Type 2 diabetes thus far. The trial enrolled more than 2,700 patients across 15 countries.
"Across seven Phase 3 studies enrolling more than 11,000 patients, Foundayo has demonstrated a consistent safety and efficacy profile," Thomas Seck, M.D., SVP of product development for Lilly Cardiometabolic Health, said in a statement Thursday.
He continued, “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.”
Aside from the lower MACE risk observed with Foundayo, Lilly’s med also showed clinically meaningful improvements from baseline on multiple cardiovascular risk factors, such as non-HDL cholesterol, systolic blood pressure, triglycerides and high-sensitivity C-reactive protein (hsCRP)—a marker of inflammation.
Foundayo’s FDA nod on April 1 formalized the opening of a new front in the obesity and broader GLP-1 commercial contest playing out between Lilly and Novo Nordisk. Until now, that competition had been waged between the company’s respective injectables for diabetes and obesity: Mounjaro and Zepbound in Lilly’s case, and Ozempic and Wegovy for Novo.
Novo got a leg up on Lilly with the approval of its own oral weight loss med, the Wegovy pill, at the tail end of 2025, which it followed up with a January 5 launch that has so far posted impressive results.
Lilly is hoping the fact that its pill can be taken at any time of day and without food or water restrictions could give Foundayo a convenience edge over oral Wegovy, which must be taken on an empty stomach in the morning with up to 4 ounces of water, and not any other liquids.