FDA
FDA requires post-marketing safety studies for newly approved Foundayo
FDA approved Foundayo (orforglipron), the first oral small molecule GLP-1 receptor agonist for obesity treatment, on April 1, 2026, but mandated post-marketing clinical trials to address four specific safety issues: major adverse cardiovascular events, drug-induced liver injury, retained gastric contents during procedures, and exposure during lactation.
Required post-marketing safety studies include:
- Cardiovascular safety:Completion of the ACHIEVE‑4 trial with adjudicated major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina, and nonfatal stroke. Peptide GLP‑1 receptor agonists have demonstrated relative risk reduction in MACE across multiple outcomes trials; however, orforglipron is a novel, non-peptide GLP‑1 receptor agonist, and whether similar cardiovascular effects will be observed remains to be established.
- Liver safety:Detailed evaluation of potential drug‑induced liver injury from ACHIEVE‑4, including Hy’s Law analyses, liver enzyme and bilirubin shift tables, and standardized case reports. Of note, earlier investigational oral GLP‑1 receptor agonists, including danuglipron, were discontinued during clinical development after liver safety signals were observed.
- Gastric emptying and aspiration risk:A clinical pharmacology study using ultrasound to assess retained gastric contents after dose interruption and fasting. GLP‑1 receptor agonists are known to delay gastric emptying, an established class effect associated with increased pulmonary aspiration risk during anesthesia and procedures, and the study is intended to inform potential recommendations aimed at mitigating this serious risk.
- Lactation exposure:A milk‑only study in lactating women to measure orforglipron levels in breast milk using a validated assay.
These studies are intended to clarify safety risks as Foundayo enters broader clinical use.
Source: U.S. Food and Drug Administration. Approval letter for Foundayo (orforglipron). April 1, 2026. Accessed April 15, 2026.