Eli Lilly reports Phase 3 ACHIEVE-4 results for Foundayo, showing non-inferior cardiovascular safety and superior A1C and weight reduction vs insulin glargine, amid FDA-requested safety data review
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company has reported positive topline results from the Phase 3 ACHIEVE-4 trial (NCT05803421) of Foundayo (orforglipron), releasing the data shortly after the U.S. Food and Drug Administration requested additional postmarketing safety data for the therapy.
Foundayo (orforglipron) was approved by the U.S. Food and Drug Administration on April 1, 2026, and launched in the U.S. on April 9 as a treatment for long-term weight management in adults.
In the global study involving more than 2,700 adults with type 2 diabetes and elevated cardiovascular risk, Foundayo met its primary endpoint by demonstrating non-inferior risk of major adverse cardiovascular events compared to insulin glargine, with a hazard ratio of 0.84 (95% CI: 0.59–1.20), reflecting a 16% lower relative risk and supporting its cardiovascular safety profile in a high-risk population.
Building on this, the therapy also showed superior metabolic outcomes at 52 weeks, including greater reductions in A1C (−1.6% vs. −1.0%) and body weight (−8.8% vs. +1.7%) compared to insulin glargine, with these benefits sustained through 104 weeks alongside improvements in key cardiovascular risk markers such as lipids and blood pressure. A pre-specified analysis further indicated a 57% lower risk of all-cause mortality (HR: 0.43; p = 0.002), although this finding was not adjusted for multiplicity and should be interpreted with caution.
The safety and tolerability profile remained consistent with the GLP-1 receptor agonist class, with gastrointestinal events including nausea, vomiting, and diarrhea being the most commonly reported adverse events, and no hepatic safety signal identified in the trial.
Against this backdrop, Thomas Seck noted that the ACHIEVE-4 data add to the growing Phase 3 evidence base, reinforcing cardiovascular safety while highlighting the potential of a once-daily oral option without food or water restrictions.
Lilly said it plans to submit Foundayo for type 2 diabetes to the FDA by the end of the second quarter, with the ACHIEVE-4 results expected to support the broader safety and efficacy package under regulatory review, positioning the therapy as a potential oral alternative in the GLP-1 class amid ongoing regulatory scrutiny.
Notably, prior to this data release, the FDA had formally required Lilly to complete the ACHIEVE-4 trial and submit detailed safety findings, including adjudicated major adverse cardiovascular events and comprehensive analyses of potential drug-induced liver injury (DILI), such as Hy’s Law assessments and liver enzyme evaluations. While the current topline results address the cardiovascular outcomes component of this request, detailed DILI data were not included in this disclosure and are expected to form part of the full clinical study report to regulators.
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About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.