Trial results for a Phase 1 drug interaction study of Orforglipron (LY3502970) with clarithromycin in healthy participants were posted on ClinicalTrials.gov on 2026-05-27. The study found that co-administration with clarithromycin significantly increased the systemic exposure of Orforglipron, with a geometric least squares mean ratio of 3.54 for AUC(0-∞).
Background
The study investigated the pharmacokinetics of Orforglipron (LY3502970) when administered alone and in combination with clarithromycin. The primary objective was to determine the blood levels of LY3502970 in healthy participants under these different administration conditions.
Trial design
The completed Phase 1 study (NCT05469126) enrolled 26 healthy participants. The trial's main purpose was to assess the pharmacokinetics of LY3502970 alone and in combination with clarithromycin. Participants were evaluated over approximately 85 days.
Key results
The trial evaluated the pharmacokinetic profile of Orforglipron (LY3502970) in the presence and absence of clarithromycin:
- For Area Under the Concentration Versus Time Curve (AUC) from time zero to infinity [AUC(0-∞)] of LY3502970:
- LY3502970 alone (Day 1) had a geometric least squares mean of 380 nanogram*hour per milliliter (ng*hr/mL) (Geometric Coefficient of Variation: 40%).
- Clarithromycin + LY3502970 (Day 21) had a geometric least squares mean of 1380 ng*hr/mL (Geometric Coefficient of Variation: 31%).
- The geometric least squares mean ratio for Clarithromycin + LY3502970 versus LY3502970 alone was 3.54 (90% Confidence Interval: 2.96, 4.22).
- For Area Under the Concentration Time Curve from time zero to time T [AUC(0-tlast)] of LY3502970:
- LY3502970 alone (Day 1) had a geometric least squares mean of 333 ng*h/ mL (Geometric Coefficient of Variation: 37%).
- Clarithromycin + LY3502970 (Day 21) had a geometric least squares mean of 1270 ng*h/ mL (Geometric Coefficient of Variation: 30%).
- The geometric least squares mean ratio for Clarithromycin + LY3502970 versus LY3502970 alone was 3.69 (90% Confidence Interval: 3.19, 4.28).
- For Maximum Observed Concentration (Cmax) of LY3502970:
- LY3502970 alone (Day 1) had a geometric least squares mean of 15.4 nanograms per milliliter (ng/mL) (Geometric Coefficient of Variation: 38%).
- Clarithromycin + LY3502970 (Day 21) had a geometric least squares mean of 30.4 ng/mL (Geometric Coefficient of Variation: 30%).
- The geometric least squares mean ratio for Clarithromycin + LY3502970 versus LY3502970 alone was 1.88 (90% Confidence Interval: 1.61, 2.19).
What this means
The results of this Phase 1 drug interaction study indicate that co-administration of Orforglipron with clarithromycin significantly increases the systemic exposure of Orforglipron in healthy participants. The geometric least squares mean ratio of 3.54 for AUC(0-∞) and 3.69 for AUC(0-tlast) suggests that Orforglipron exposure more than triples when taken with clarithromycin. Similarly, the maximum observed concentration (Cmax) nearly doubles, with a ratio of 1.88. These findings highlight a potential drug-drug interaction that could be clinically significant. Further evaluation would be necessary to determine if dose adjustments or specific precautions are required when Orforglipron is co-administered with clarithromycin or other drugs that may have similar metabolic effects.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05469126, titled "A Drug Interaction Study of Clarithromycin and LY3502970 in Healthy Participants", were posted on 2026-05-27 on clinicaltrials.gov.