Results from a Phase 3 long-term safety study of Orforglipron in participants with Type 2 Diabetes were posted on 2026-06-30. The trial demonstrated significant dose-dependent reductions in Hemoglobin A1c (HbA1c), with the highest dose achieving a least squares mean change of -2.13%. Additionally, up to 90.82% of participants on the highest dose achieved an HbA1c below 7.0%.
Background
Orforglipron is an investigational drug being studied for the treatment of Type 2 Diabetes. This condition is characterized by high blood sugar levels resulting from insulin resistance or insufficient insulin production, leading to various health complications if not managed effectively.
Trial design
The completed Phase 3 study, titled "A Long-term Safety Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes," enrolled 401 participants. The trial investigated the long-term safety of orforglipron as a monotherapy or in combination with oral antihyperglycemic medication in individuals with Type 2 Diabetes. The study included a 52-week treatment period with a 20-week dose escalation phase, followed by a 2-week safety follow-up.
Key results
The trial reported the number of participants experiencing Treatment Emergent Adverse Events (TEAEs) across different dose groups. For the 3 mg Orforglipron group, 107 Participants experienced TEAEs. In the 12 mg Orforglipron group, 114 Participants experienced TEAEs, and for the 36 mg Orforglipron group, 118 Participants experienced TEAEs.
Regarding efficacy, significant reductions in Hemoglobin A1c (HbA1c) from baseline were observed. The 3 mg Orforglipron group showed a least squares mean change of -1.71 percentage of HbA1c (Standard Error: 0.072). The 12 mg Orforglipron group achieved a least squares mean change of -1.97 percentage of HbA1c (Standard Error: 0.075). The highest dose, 36 mg Orforglipron, resulted in a least squares mean change of -2.13 percentage of HbA1c (Standard Error: 0.073).
Achievement of glycemic targets was also measured. For an HbA1c <7.0%, the mean percentage of participants was 82.73% (Standard Error: 3.25) in the 3 mg group, 86.11% (Standard Error: 2.86) in the 12 mg group, and 90.82% (Standard Error: 2.52) in the 36 mg group.
For an even stricter target of HbA1c ≤6.5%, the mean percentage of participants was 62.64% (Standard Error: 4.11) in the 3 mg group, 76.23% (Standard Error: 3.57) in the 12 mg group, and 84.56% (Standard Error: 3.27) in the 36 mg group.
What this means
The results from this Phase 3 study suggest that Orforglipron, when administered as monotherapy or in combination with other oral antihyperglycemic medications, can effectively lower HbA1c levels in patients with Type 2 Diabetes. The observed dose-dependent reductions in HbA1c and the high percentages of participants achieving glycemic targets (<7.0% and ≤6.5%) are clinically meaningful. The reporting of Treatment Emergent Adverse Events (TEAEs) across the dose groups provides initial insights into the long-term safety profile of the drug, which will be crucial for its potential development and regulatory review.
Source
These trial results were posted on 2026-06-30 by ClinicalTrials.gov, an official database of clinical studies. The full details of the study, "A Long-term Safety Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes," are available on clinicaltrials.gov.