Trial results for a Phase 1 study of Orforglipron (LY3502970) in healthy male participants were posted on ClinicalTrials.gov on 2026-05-26. The study investigated the pharmacokinetics and excretion of a single dose of the radiolabeled drug, revealing that an average of 86.75% of the total radioactive dose was excreted in feces.
Background
This Phase 1 study aimed to characterize the absorption, distribution, metabolism, and excretion (ADME) profile of Orforglipron. Specifically, it sought to measure how much of the study drug enters the bloodstream, its elimination characteristics, and the pathways through which the drug and its breakdown products are excreted from the body following a single dose of radiolabeled [¹⁴C]-LY3502970.
Trial design
The completed Phase 1 study (NCT04680767) enrolled 6 healthy male participants. The trial administered a single 3mg dose of [¹⁴C]-LY3502970 to investigate its pharmacokinetics, including systemic exposure, and the excretion of the drug and its metabolites in urine and feces. The study duration was up to 8 weeks.
Key results
The study provided detailed pharmacokinetic and excretion data:
- Feces excretion of LY3502970 radioactivity over time was a mean of 86.75% (Standard Deviation 2.78%) of the total radioactive dose administered.
- Urinary excretion of LY3502970 radioactivity over time was a mean of 0.24% (Standard Deviation 0.02%) of the total radioactive dose administered.
- Pharmacokinetics for plasma LY3502970 showed an Area Under the Concentration Versus Time Curve from time zero to the last measurable concentration (AUC0-Tlast) of 210 nanogram*hour per milliliter (Geometric Coefficient of Variation 14%) and from time zero to infinity (AUC0-∞) of 223 nanogram*hour per milliliter (Geometric Coefficient of Variation 13%).
- The Maximum Concentration (Cmax) of plasma LY3502970 was 10.4 nanogram per milliliter (Geometric Coefficient of Variation 14%).
- For total radioactivity in plasma and whole blood, the AUC0-Tlast values were 266 nanogram equivalents*hour per milliliter (Geometric Coefficient of Variation 21%) and 103 nanogram equivalents*hour per milliliter (Geometric Coefficient of Variation 19%).
- For total radioactivity in plasma and whole blood, the AUC0-∞ values were 292 nanogram equivalents*hour per milliliter (Geometric Coefficient of Variation 21%) and 135 nanogram equivalents*hour per milliliter (Geometric Coefficient of Variation 17%).
- For total radioactivity in plasma and whole blood, the Cmax values were 10.7 nanogram equivalents per milliliter (Geometric Coefficient of Variation 17%) and 5.92 nanogram equivalents per milliliter (Geometric Coefficient of Variation 16%).
- A total of 2 metabolites of LY3502970 were identified in plasma, urine, and feces.
What this means
These Phase 1 pharmacokinetic results indicate that Orforglipron is predominantly eliminated through fecal excretion, with a mean of 86.75% of the administered radioactive dose recovered in feces, compared to a minimal 0.24% in urine. This suggests that renal function may not be a primary determinant of Orforglipron clearance. The identification of 2 metabolites in plasma, urine, and feces also provides initial insights into the drug's metabolic profile. These early-phase data are crucial for guiding further clinical development, including dose selection and potential considerations for patient populations with varying organ functions.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04680767, titled "A Study of LY3502970 in Healthy Male Participants", were posted on 2026-05-26 on clinicaltrials.gov.