Trial results for a Phase 1 drug-drug interaction study evaluating orforglipron in healthy overweight and obese participants were posted on ClinicalTrials.gov on 2026-05-22. The study investigated the pharmacokinetic profile of co-administered drugs, including simvastatin, with specific measurements for simvastatin acid AUC[0-∞] ranging from 13.6 ng*h/ml to 30.2 ng*h/ml across various administration scenarios.
Background
Orforglipron is an investigational drug. This study focused on its potential drug-drug interactions with commonly used medications such as simvastatin, digoxin, rosuvastatin, and acetaminophen. Understanding these interactions is crucial for assessing the safety and appropriate dosing of orforglipron when co-administered with other therapies.
Trial design
The Phase 1 study (NCT06186622) enrolled 50 participants who were healthy, overweight, or obese. The main purpose was to determine the effect of orforglipron capsule formulation on the pharmacokinetics of co-administered digoxin, rosuvastatin, acetaminophen, midazolam, and simvastatin. It also evaluated the effect of the orforglipron tablet on simvastatin pharmacokinetics. Various administration methods, including simultaneous and staggered dosing, were assessed.
Key results
The study posted detailed pharmacokinetic results for simvastatin and its metabolite, simvastatin acid, under various co-administration conditions with orforglipron capsule formulation and sodium bicarbonate. Key findings for the Area Under the Concentration-Time Curve from time zero to infinity (AUC[0-∞]) for simvastatin acid include:
- When 20 mg Simvastatin was administered alone, the geometric mean AUC[0-∞] for simvastatin acid ranged from 13.6 ng*h/ml (Geometric Coefficient of Variation: 79.7%) to 22.1 ng*h/ml (Geometric Coefficient of Variation: 79.2%).
- Following simultaneous administration of 36 mg Orforglipron Capsule + 20 mg Simvastatin, the geometric mean AUC[0-∞] for simvastatin acid varied, with values of 18.8 ng*h/ml (Geometric Coefficient of Variation: 84.3%) and 23.3 ng*h/ml (Geometric Coefficient of Variation: 74.2%) reported across different cohorts.
- With staggered administration of 36 mg Orforglipron Capsule + 20 mg Simvastatin, the geometric mean AUC[0-∞] for simvastatin acid was observed at 20.1 ng*h/ml (Geometric Coefficient of Variation: 76.5%) and 30.2 ng*h/ml (Geometric Coefficient of Variation: 70.3%).
- For simultaneous administration of 20 mg Simvastatin + 600 mg Sodium Bicarbonate, the geometric mean AUC[0-∞] for simvastatin acid was 20.3 ng*h/ml (Geometric Coefficient of Variation: 82.8%) and 14.0 ng*h/ml (Geometric Coefficient of Variation: 61.3%).
What this means
The posted results from this Phase 1 drug-drug interaction study provide initial pharmacokinetic data for orforglipron when co-administered with simvastatin and sodium bicarbonate. The observed variability in simvastatin and simvastatin acid AUC[0-∞] values suggests that orforglipron may influence the systemic exposure of co-administered drugs depending on the specific drug, formulation, and administration timing. These findings are important for understanding potential drug interactions and will inform future clinical development, including potential dose adjustments or monitoring recommendations for orforglipron when used alongside other medications. Further analysis of the full pharmacokinetic profile, including other co-administered drugs like digoxin, rosuvastatin, and acetaminophen, would provide a more comprehensive understanding of its interaction potential.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT06186622, titled "A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants", were posted on 2026-05-22 on clinicaltrials.gov.