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Orforglipron cardiovascular safety: what ACHIEVE-4 found
Catch-up: original trial paper published 30 September 2026; this summary uses its indexed abstract.
ACHIEVE-4 compared daily oral orforglipron with insulin glargine in adults with type 2 diabetes and increased cardiovascular risk. The Phase 3, randomised, open-label trial assigned 2,749 participants and followed them for a median of two years.
Orforglipron met the prespecified non-inferiority test for a composite of cardiovascular death, non-fatal heart attack, non-fatal stroke or hospitalisation for unstable angina. The hazard ratio was 0.84 (95% confidence interval 0.59–1.20). This does not demonstrate cardiovascular superiority.
Gastrointestinal adverse events were more common with orforglipron; clinically significant or severe hypoglycaemia was less common. The study was funded by Lilly. SHIFT checked the original indexed abstract; the full paper was not independently available for this review.
SHIFT’s take
Observed trial outcomes should be distinguished from separate studies that model predicted future risk. These results concern the studied diabetes population, not every person seeking weight loss.
Known facts
- The original paper was electronically published on 30 September 2026.