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# Orforglipron against insulin glargine in the ACHIEVE-4 cardiovascular safety trial
- URL: https://www.coios.me/orforglipron-against-insulin-glargine-in-the-achieve-4/
- Published: 2026-10-03T13:20:53.000Z
- Updated: 2026-10-03T17:26:53.000Z
- Description: ACHIEVE-4 randomised 2749 adults with type 2 diabetes, overweight or obesity and established cardiovascular or kidney disease to oral orforglipron or insulin glargine, testing non-inferiority for four-component major adverse cardiovascular events over a median two years.
- Author: Daniel Ryan
- Tags: Tomorrow's world, Innovation in treatment, Heart and stroke, Obesity, diabetes and GLP-1, World, #peer-reviewed, #new, #item, #source-2026-09

The open-label trial compared orforglipron, an oral non-peptide GLP-1 receptor agonist, with titrated insulin glargine in 2749 adults with type 2 diabetes at increased cardiovascular risk, of whom 86% had established cardiovascular disease and 38% chronic kidney disease. The primary outcome was time to cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for unstable angina, with non-inferiority declared if the upper limit of the 95% confidence interval for the hazard ratio was below 1.8.

*Why it is interesting: Cardiovascular safety of a non-peptide GLP-1 receptor agonist set against an active comparator, with a stated non-inferiority margin of 1.8 on the hazard ratio.*

Source

[The Lancet, 30 September 2026](https://doi.org/10.1016/s0140-6736%2826%2901865-9?ref=coios.me)

DOI

10.1016/s0140-6736(26)01865-9

Type

Peer-reviewed article

Design

Phase 3 event-driven randomised open-label active-comparator non-inferiority trial, 2749 adults, 317 sites in 16 countries, median follow-up 2 years, 2023-2024

Verdict

New finding

Driver

[Innovation in treatment](https://www.coios.me/d-treatment-innovation/)

Driver

[Heart and stroke](https://www.coios.me/d-cardiovascular/)

Driver

[Obesity, diabetes and GLP-1](https://www.coios.me/d-obesity-diabetes/)