Trial results for Orforglipron (LY3502970) in healthy overweight and obese participants were posted on 2026-07-10. The PHASE1 study (NCT05841238) primarily evaluated the pharmacokinetics of various oral tablet and capsule formulations, demonstrating a dose-dependent increase in drug exposure. For instance, the 0.8 mg tablet showed a geometric mean AUC[0-24] of 90.8 nanogram*hour per milliliter (ng*h/mL), while the 37.5 mg tablet achieved 3680 ng*h/mL.

Background

Orforglipron (LY3502970) was investigated in healthy individuals who were overweight or obese. The study aimed to understand how the drug is absorbed into the bloodstream and eliminated from the body, as well as its safety and tolerability.

Trial design

The study, identified as NCT05841238, was a PHASE1 multiple-dose study that enrolled 52 participants. Participants included individuals who were healthy, overweight, or obese. The study's main purpose was to evaluate the pharmacokinetics of LY3502970 when administered orally as tablet and capsule formulations, including the effect of food. It also assessed the safety and tolerability of LY3502970 in these participants.

Key results

The primary pharmacokinetic outcome measured was the Area Under the Concentration Versus Time Curve from Time Zero to the 24 Hour Time Point (AUC[0-24]) of LY3502970 in a fasted state across various doses and formulations. The geometric mean AUC[0-24] values were:

  • For 0.8 mg LY3502970 Tablet: 90.8 ng*h/mL (Geometric Coefficient of Variation: 27%)
  • For 2 mg LY3502970 Capsule: 199 ng*h/mL (Geometric Coefficient of Variation: 34%)
  • For 2.5 mg LY3502970 Tablet: 294 ng*h/mL (Geometric Coefficient of Variation: 31%)
  • For 5 mg LY3502970 Tablet: 548 ng*h/mL (Geometric Coefficient of Variation: 29%)
  • For 8 mg LY3502970 Capsule: 700 ng*h/mL (Geometric Coefficient of Variation: 42%)
  • For 10 mg LY3502970 Tablet: 1080 ng*h/mL (Geometric Coefficient of Variation: 32%)
  • For 16 mg LY3502970 Capsule: 1250 ng*h/mL (Geometric Coefficient of Variation: 40%)
  • For 20 mg LY3502970 Tablet: 1970 ng*h/mL (Geometric Coefficient of Variation: 48%)
  • For 36 mg LY3502970 Capsule: 1580 ng*h/mL (Geometric Coefficient of Variation: 72%)
  • For 37.5 mg LY3502970 Tablet: 3680 ng*h/mL (Geometric Coefficient of Variation: 47%)
  • For 35 mg LY3502970 Tablet (Part B, Period 12): 3730 ng*h/mL (Geometric Coefficient of Variation: 37%)
  • For 35 mg LY3502970 Tablet (Part B, Period 13): 4080 ng*h/mL (Geometric Coefficient of Variation: 40%)

These results indicate an increase in systemic exposure (AUC[0-24]) with increasing doses of Orforglipron across both tablet and capsule formulations.

What this means

The pharmacokinetic data from this PHASE1 study provides essential information on how Orforglipron is absorbed and processed by the body at various oral doses and formulations. The observed dose-dependent increase in exposure is a critical finding for establishing appropriate dosing regimens in future clinical trials. While the study also evaluated safety and tolerability, specific adverse event summaries were not detailed in the posted results.

Source

These trial results were posted on ClinicalTrials.gov on 2026-07-10. The full details of the study, NCT05841238, are available on clinicaltrials.gov.