Results from a PHASE3 study (NCT05931380) investigating once-daily oral Orforglipron in Japanese adult participants with obesity were posted on 2026-07-20. The trial demonstrated that the 12 mg dose of Orforglipron led to a least squares mean body weight reduction of -8.69% at Week 72, significantly outperforming placebo which showed a reduction of -0.63%.

Background

Orforglipron is an investigational drug studied for the treatment of Obesity. This study focused on its efficacy and safety in Japanese adults.

Trial design

The PHASE3 study, identified as NCT05931380, enrolled 238 participants with Obesity. The main purpose of this study was to investigate the efficacy and safety of oral Orforglipron in participants with obesity disease with obesity-related health problems. Participants were randomized to receive once-daily oral doses of Orforglipron (6 mg, 12 mg, or 36 mg) or placebo.

Key results

At Week 72, the percent change from baseline in body weight showed dose-dependent reductions across the Orforglipron arms compared to placebo:

  • Placebo QD: -0.63% (Standard Error 0.732)
  • 6 mg Orforglipron QD: -5.90% (Standard Error 0.866)
  • 12 mg Orforglipron QD: -8.69% (Standard Error 1.136)
  • 36 mg Orforglipron QD: -7.93% (Standard Error 1.063)

Statistical analyses for the least squares mean difference in body weight change from baseline at Week 72, compared to placebo, showed significant differences (all p-values 0.001):

  • 6 mg Orforglipron QD vs. Placebo: -5.28% (95% Confidence Interval -7.52, -3.03)
  • 12 mg Orforglipron QD vs. Placebo: -8.06% (95% Confidence Interval -10.72, -5.39)
  • 36 mg Orforglipron QD vs. Placebo: -7.3% (95% Confidence Interval -9.81, -4.78)

The study also reported the percentage of participants achieving specific body weight reductions from baseline:

  • Percentage of Participants Who Achieved ≥5% Body Weight Reduction From Baseline:
    • Placebo QD: 15.00%
    • 6 mg Orforglipron QD: 45.90%
    • 12 mg Orforglipron QD: 61.40%
    • 36 mg Orforglipron QD: 58.33%
  • Percentage of Participants Who Achieved ≥10% Body Weight Reduction From Baseline:
    • Placebo QD: 3.33%
    • 6 mg Orforglipron QD: 18.03%
    • 12 mg Orforglipron QD: 35.09%
    • 36 mg Orforglipron QD: 38.33%

Statistical analyses for the risk difference in achieving ≥5% body weight reduction from baseline, compared to placebo, were also significant (all p-values 0.001):

  • 6 mg Orforglipron QD vs. Placebo: 30.36% (95% Confidence Interval 15.09, 45.62)
  • 12 mg Orforglipron QD vs. Placebo: 45.54% (95% Confidence Interval 29.64, 61.44)
  • 36 mg Orforglipron QD vs. Placebo: 43.53% (95% Confidence Interval 27.71, 59.35)

What this means

The results from this PHASE3 study indicate that once-daily oral Orforglipron significantly reduces body weight in Japanese adults with obesity. The observed dose-dependent reductions in body weight and the higher rates of achieving clinically meaningful weight loss (≥5% and ≥10%) across the Orforglipron treatment arms, compared to placebo, suggest a strong efficacy profile. These findings support the potential of Orforglipron as an effective treatment option for obesity.

Source

This information was sourced from ClinicalTrials.gov, documenting the results of trial NCT05931380, which were posted on 2026-07-20. The study details are available on clinicaltrials.gov.