Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.

Orforglipron demonstrates non-inferior cardiovascular safety compared to insulin glargine in adults with type 2 diabetes at increased cardiovascular risk, with a hazard ratio of 0.84.

• Why it matters: Cardiovascular safety is crucial for diabetes treatments, especially for high-risk populations, but the safety profile of non-peptide GLP-1 receptor agonists like orforglipron has not been established.
• What they did: A phase 3, randomized, open-label trial involving 2749 participants compared orforglipron (up to 36 mg daily) with insulin glargine over a median of 2 years, assessing major adverse cardiovascular events (MACE-4).
• The result: Orforglipron was found to be non-inferior to insulin glargine for MACE-4, with fewer hypoglycemia episodes and deaths, supporting its use as a safe, oral treatment option for high-risk type 2 diabetes patients.