Trial results for a Phase 1 drug interaction study of Orforglipron (LY3502970) were posted on ClinicalTrials.gov on 2026-05-26. The study in healthy participants found that co-administration with cyclosporine significantly increased Orforglipron's exposure, with its area under the concentration versus time curve (AUC) showing a 2.55-fold increase.
Background
This study investigated the pharmacokinetic interaction between Orforglipron (LY3502970) and cyclosporine. The primary objective was to determine the blood levels of Orforglipron when administered alone and in combination with cyclosporine in healthy participants, as well as to evaluate its safety and tolerability.
Trial design
The Phase 1 study (NCT05573230) was a drug interaction study that enrolled 32 healthy participants. The study evaluated the pharmacokinetics of Orforglipron (LY3502970) when administered alone and in combination with cyclosporine. Participants were studied over approximately 76 days.
Key results
The study measured the pharmacokinetics of Orforglipron (LY3502970) in healthy participants:
- For the Area Under the Concentration Versus Time Curve (AUC) of Orforglipron:
- When administered alone (Reference), the geometric mean AUC was 332 ng*hr/mL (Geometric Coefficient of Variation: 39%).
- When co-administered with cyclosporine (Test), the geometric mean AUC was 857 ng*hr/mL (Geometric Coefficient of Variation: 51%).
- For the Maximum Observed Concentration (Cmax) of Orforglipron:
- When administered alone (Reference), the geometric mean Cmax was 13.9 ng/mL (Geometric Coefficient of Variation: 48%).
- When co-administered with cyclosporine (Test), the geometric mean Cmax was 18.4 ng/mL (Geometric Coefficient of Variation: 36%).
A mixed models analysis comparing the test and reference groups showed:
- The Geometric LS Mean Ratio for AUC of Orforglipron when co-administered with cyclosporine was 2.55 (90.0% Confidence Interval: 2.07, 3.14).
- The Geometric LS Mean Ratio for Cmax of Orforglipron when co-administered with cyclosporine was 1.29 (90.0% Confidence Interval: 1.0, 1.66).
What this means
The results of this Phase 1 study indicate a significant pharmacokinetic interaction between Orforglipron and cyclosporine. The geometric mean ratio of 2.55 for the AUC suggests that cyclosporine co-administration more than doubles the systemic exposure to Orforglipron. Similarly, the Cmax also increased, though to a lesser extent, with a geometric mean ratio of 1.29. These findings are crucial for understanding the potential need for dose adjustments or specific monitoring when Orforglipron is prescribed to patients also taking cyclosporine, to manage efficacy and safety profiles effectively. Further clinical guidance will be necessary based on these interaction data.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05573230, titled "A Drug Interaction Study of Cyclosporine and LY3502970 in Healthy Participants", were posted on 2026-05-26 on clinicaltrials.gov.