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NVO REDEFINE 4: CagriSema Fails Non-Inferiority vs LLY Tirzepatide

Matt RuncheySHORELINE, WA — February 23, 2026 · 11:00 AM PST2 min
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Disclosure: As of 2026-02-10, the Runchey Research Model Trading Fund holds a long position in NVO. View our full Editorial Integrity & Disclosure Policy.

Novo Nordisk's CagriSema achieved 23.0% weight loss in the REDEFINE 4 trial — but lost the head-to-head battle against Eli Lilly's tirzepatide on the study's primary endpoint of non-inferiority. Our CagriSema efficacy market resolves NO, a miss for the ensemble which had predicted 62% YES.

23.0%
CagriSema (NVO)
On-treatment estimand
25.5%
Tirzepatide (LLY)
On-treatment estimand
Failed
Non-Inferiority
CI exceeded margin
0.38
Brier Score
Predicted 62% YES

What the Data Shows

REDEFINE 4 was designed to prove CagriSema's non-inferiority to tirzepatide 15mg. While CagriSema delivered 23.0% weight loss (on-treatment) and 20.2% (ITT), tirzepatide achieved 25.5% and 23.6% respectively — a 2.5–3.4 percentage point absolute advantage. The lower bound of the confidence interval exceeded the pre-specified non-inferiority margin, meaning the trial officially did not meet its primary endpoint.

Where the Ensemble Went Wrong
All 9 model runs correctly assessed that CagriSema would likely exceed 20% weight loss — it did. The miss was a resolution-criteria reading failure: models focused on the absolute weight loss threshold without adequately weighting clause (b), which triggers NO if the trial fails its primary endpoint. The primary endpoint was comparative (non-inferiority to tirzepatide), not absolute. Opus run 2 was the most skeptical at 54% and scored best (Brier 0.29).
Competitive Implications
For LLY, this data reinforces tirzepatide's position as the best-in-class GLP-1 for weight loss. For NVO, CagriSema remains highly effective in isolation but demonstrably inferior to the market leader — consistent with the Moat Mapper's “managed decline to strong #2 position” scenario. The COMPETITIVE_POSITION signal remains CONTESTED. Seven NVO forecast markets remain active.

View all 7 active NVO forecast markets and ensemble predictions

NVO Forecast Markets

This report was generated by the Runchey Research AI Ensemble using primary SEC data and reviewed by Matthew Runchey for accuracy.

This analysis is for educational purposes only and does not constitute investment advice. See our Editorial Integrity & Disclosure Policy and Terms of Service.