The Phase 3 trial for Orforglipron (NCT05971940) in adult participants with Type 2 Diabetes reached primary completion on 2025-04-03. Results showed that Orforglipron significantly reduced HbA1c levels, with the 12 mg dose achieving a least squares mean change of -1.59 percentage of HbA1c compared to -0.15 percentage of HbA1c for placebo.
Background
The study investigated Orforglipron for adult participants diagnosed with Type 2 Diabetes who had inadequate glycemic control with diet and exercise alone.
Trial design
The study (NCT05971940) was a Phase 3 trial that enrolled 559 adult participants with Type 2 Diabetes and inadequate glycemic control with diet and exercise alone. The main purpose was to determine the safety and efficacy of Orforglipron compared with placebo. Participants received either Orforglipron at doses of 3 mg, 12 mg, or 36 mg, or placebo. The study duration was approximately 54 weeks.
Key results
The trial evaluated the change from baseline in HbA1c and the percentage of participants achieving target HbA1c values.
- For "Change From Baseline in HbA1c" (Least Squares Mean):
- Placebo: -0.15 percentage of HbA1c (Standard Error: 0.113)
- 3 mg Orforglipron: -1.26 percentage of HbA1c (Standard Error: 0.114)
- 12 mg Orforglipron: -1.59 percentage of HbA1c (Standard Error: 0.087)
- 36 mg Orforglipron: -1.45 percentage of HbA1c (Standard Error: 0.104)
- For "Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol)":
- Placebo: 37.11 percentage of participants
- 3 mg Orforglipron: 78.15 percentage of participants
- 12 mg Orforglipron: 81.25 percentage of participants
- 36 mg Orforglipron: 78.99 percentage of participants
- For "Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol)":
- Placebo: 18.56 percentage of participants
- 3 mg Orforglipron: 66.39 percentage of participants
- 12 mg Orforglipron: 68.75 percentage of participants
- 36 mg Orforglipron: 68.91 percentage of participants
Key analyses comparing Orforglipron to placebo demonstrated significant differences:
- For change from baseline in HbA1c, the Least Square (LS) Mean Difference (Net) for 3 mg Orforglipron versus placebo was -1.12 (95.0% CI: -1.43 to -0.8, p-value: 0.001).
- For change from baseline in HbA1c, the LS Mean Difference (Net) for 12 mg Orforglipron versus placebo was -1.44 (95.0% CI: -1.72 to -1.16, p-value: 0.001).
- For change from baseline in HbA1c, the LS Mean Difference (Net) for 36 mg Orforglipron versus placebo was -1.30 (95.0% CI: -1.61 to -1.0, p-value: 0.001).
- For achieving an HbA1c target value of < 7.0%, the Risk Difference (RD) for 3 mg Orforglipron versus placebo was 44.9 (95.0% CI: 34.41 to 55.39, p-value: 0.001).
- For achieving an HbA1c target value of < 7.0%, the Risk Difference (RD) for 12 mg Orforglipron versus placebo was 48.22 (95.0% CI: 37.5 to 58.93, p-value: 0.001).
- For achieving an HbA1c target value of < 7.0%, the Risk Difference (RD) for 36 mg Orforglipron versus placebo was 46.94 (95.0% CI: 36.61 to 57.28, p-value: 0.001).
What this means
The results indicate that Orforglipron, across multiple doses, significantly improved glycemic control in adults with Type 2 Diabetes compared to placebo. The substantial reductions in HbA1c and the higher proportion of participants achieving target HbA1c levels suggest that Orforglipron could be an effective oral treatment option for managing Type 2 Diabetes. These findings provide important data for clinicians considering therapeutic strategies for glycemic control.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The primary completion status and results for study NCT05971940, titled "A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone," were posted on 2025-04-03 on clinicaltrials.gov.