Trial results for a Phase 1 study evaluating Orforglipron (LY3502970) in participants with Type 2 Diabetes were posted on ClinicalTrials.gov on 2026-05-26. The study reported no serious adverse events (SAEs) considered related to the study drug across all active treatment arms, while one SAE was reported in the placebo group. The trial also provided pharmacokinetic data for various dosing regimens.
Background
The study investigated Orforglipron (LY3502970) for participants with Type 2 Diabetes. This Phase 1 trial aimed to assess the safety profile, potential side effects, and pharmacokinetic properties of the drug.
Trial design
The Phase 1 study (NCT04426474) enrolled 68 participants with Type 2 Diabetes. The main purpose of the study was to learn more about the safety of LY3502970 and any associated side effects, as well as to measure its concentration in the bloodstream and its elimination. The trial included various dosing regimens of LY3502970 compared to placebo.
Key results
The trial reported the following key safety and pharmacokinetic outcomes:
- For serious adverse events (SAEs) considered related to the study drug:
- In the Placebo QD group, 1 participant experienced an SAE.
- Across all LY3502970 QD dosing groups (3/6/12/21 mg, 3/6/9 mg, 3/6/12/15 mg, 3/6/12/21/27 mg, and 3/6/9/21/36/45 mg), 0 participants experienced an SAE.
- Pharmacokinetic data for Maximum Observed Concentration (Cmax) of LY3502970:
- For the 3/6/12/21 mg LY3502970 QD group, the geometric mean Cmax was 101 nanograms/milliliter (ng/mL) with a geometric coefficient of variation of 28.
- For the 3/6/9 mg LY3502970 QD group, the geometric mean Cmax was 57.9 ng/mL with a geometric coefficient of variation of 78.
- For the 3/6/12/15 mg LY3502970 QD group, the geometric mean Cmax was 97.9 ng/mL with a geometric coefficient of variation of 30.
- For the 3/6/12/21/27 mg LY3502970 QD group, the geometric mean Cmax was 191 ng/mL with a geometric coefficient of variation of 59.
- For the 3/6/9/21/36/45 mg LY3502970 QD group, the geometric mean Cmax was 218 ng/mL with a geometric coefficient of variation of 40.
- Pharmacokinetic data for Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours [AUC(0-24)] of LY3502970:
- For the 3/6/12/21 mg LY3502970 QD group, the geometric least squares mean AUC(0-24) was 1480 nanograms hour per milliliter (ng*h/mL) with a geometric coefficient of variation of 23.
- Key analyses included Least Squares Mean Differences and Differences in Estimated Mean Change, with values such as -0.87 (90.0% CI: -2.15, 0.4), -1.86 (90.0% CI: -3.07, -0.65), -1.7 (90.0% CI: -2.91, -0.5), -1.28 (90.0% CI: -2.52, -0.03), -1.14 (90.0% CI: -2.35, 0.07), and -2.5 (90.0% CI: -30.82, 25.83). The specific outcomes these analyses refer to are not detailed in the posted data.
What this means
The results from this Phase 1 trial for Orforglipron in Type 2 Diabetes indicate a favorable safety profile, with no serious adverse events considered related to the study drug reported in any of the active treatment arms. This contrasts with 1 participant in the placebo group experiencing a drug-related SAE. The pharmacokinetic data provides insights into the drug's absorption and exposure across various dosing regimens, which is crucial for determining optimal dosing in future studies. While the specific clinical significance of the reported mean differences from the key analyses is not detailed, the overall safety findings are encouraging for the continued development of Orforglipron as a potential treatment for Type 2 Diabetes.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04426474, titled "A Study of LY3502970 in Participants With Type 2 Diabetes", were posted on 2026-05-26 on clinicaltrials.gov.