Novo Nordisk reported results from its REDEFINE 4 trial in late February 2026, a head-to-head, open-label study comparing its experimental amylin/GLP-1 combination CagriSema against Eli Lilly's already-approved GLP-1/GIP drug tirzepatide. CagriSema produced substantial weight loss, but it did not meet the trial's primary goal of statistical non-inferiority to tirzepatide.

What the Trial Measured

REDEFINE 4 enrolled 809 adults with obesity and at least one weight-related health condition, with an average baseline body weight of about 114 kilograms. The trial compared CagriSema at its 2.4 mg/2.4 mg dose against tirzepatide at 15 mg, with the primary endpoint being whether CagriSema's weight loss was statistically non-inferior to tirzepatide's, meaning not meaningfully worse, within a pre-specified margin.

The Results

By the trial's intent-to-treat analysis, participants on CagriSema lost an average of 23 percent of body weight, compared with 25.5 percent for those on tirzepatide. Using a stricter "treatment regimen" analysis that accounts only for people who stayed on the assigned dose, the figures were 20.2 percent for CagriSema versus 23.6 percent for tirzepatide. The gap was large enough that the trial did not reach its non-inferiority threshold, meaning Novo Nordisk cannot claim CagriSema matched tirzepatide's weight-loss effect in this study.

How the Companies Responded

Novo Nordisk's chief scientific officer struck a measured tone, saying the company was "pleased with the weight loss of 23 percent for CagriSema in this open-label trial" and noting that CagriSema, if approved, would be the first GLP-1/amylin combination product on the market. The company pointed to its ongoing REDEFINE 11 trial as a further readout on CagriSema's long-term weight-loss potential.

Why "Open-Label" Matters Here

REDEFINE 4 was an open-label trial, meaning both participants and researchers knew which drug each person was taking, rather than a blinded comparison. Open-label designs are common in trials comparing two active drugs, since it's usually impractical to disguise an injectable device or dosing schedule, but they carry a higher risk of expectation effects influencing behavior or reporting than a fully blinded trial would. That doesn't invalidate the weight-loss numbers, which were objectively measured, but it's a relevant detail when weighing how much confidence to place in secondary, more subjective outcomes from the same study.

Regulatory and Market Context

Neither CagriSema nor tirzepatide's outcome in this specific trial changes their current FDA status: tirzepatide is already FDA-approved as Mounjaro and Zepbound, while CagriSema remains an investigational drug that has not yet completed the approval process. A missed non-inferiority endpoint in one head-to-head trial does not necessarily end a drug's development, but it does complicate the marketing case Novo Nordisk hoped to make against its chief rival's leading obesity drug, at a time when Eli Lilly has already been gaining market share.

What Comes Next

A missed non-inferiority endpoint in one trial is not necessarily the end of CagriSema's development. Novo Nordisk has pointed to its REDEFINE 11 trial as a further data point on the drug's long-term weight-loss ceiling, and companies frequently continue pursuing approval for a drug that shows strong, if not category-leading, efficacy, particularly one with a novel mechanism like the amylin/GLP-1 combination CagriSema represents. The amylin component is worth noting on its own: it works through a different receptor pathway than GLP-1 alone, and some researchers think amylin-based combinations may eventually offer a distinct side-effect profile or maintenance advantage even without beating tirzepatide on raw weight-loss percentage.

Talk to a Doctor

Trial results like these are useful for understanding a drug's evidence base, not for self-directed treatment decisions. Anyone weighing GLP-1 or amylin-based therapies for obesity should discuss individual health history, other medications, and realistic expectations with a licensed physician.