The LancetOriginal article
[Articles] 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
Phase 3positiveorforgliproninsulin glarginePositive
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Summary
Achieve Therapeutics' ACHIEVE-4 Phase 3 trial demonstrated that orforglipron achieved non-inferiority to insulin glargine for cardiovascular safety (MACE-4) in type 2 diabetes patients at increased cardiovascular risk, with lower rates of clinically significant hypoglycemia, supporting potential approval as a once-daily oral treatment option.
Clinical Trial Data
Phase
Phase 3
Primary Endpoint
Met
Outcome Details
Orforglipron demonstrated non-inferiority to insulin glargine for MACE-4 with confirmed cardiovascular safety. Gastrointestinal adverse events were most frequent; clinically significant hypoglycemia occurred less frequently with orforglipron than insulin glargine.
Importance:7/10
Sentiment:
0.75
Phase 3 datacardiovascular safetytype 2 diabetesMACE endpointnon-inferiority trialoral medication
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Published by The Lancet on September 30, 2026 10:01 PM