Novo Nordisk (NOVO) Study result summary

Study design and objectives

• REDEFINE 4 was an open-label, phase III trial with 809 adults with obesity and comorbidities, comparing CagriSema 2.4 mg to tirzepatide 15 mg over 84 weeks, primarily in the U.S.

• The primary endpoint was to confirm non-inferiority of CagriSema versus tirzepatide in percentage body weight change over 84 weeks.

• Both drugs were administered once weekly via subcutaneous injection, with dose modifications allowed and regimens consistent with prior REDEFINE trials.

• The open-label design was due to tirzepatide's commercial availability only in pen format, and all participants and investigators were aware of treatment assignments.

Key efficacy and safety results

• CagriSema achieved a 23% mean body weight reduction, while tirzepatide achieved 25.5% after 84 weeks, starting from a mean baseline of 140.2 kg.

• The primary endpoint of non-inferiority was not met, as CagriSema did not match tirzepatide's weight loss efficacy.

• Both treatments showed safety and tolerability profiles consistent with previous studies, with gastrointestinal events being the most common and generally mild to moderate.

• More patients in the tirzepatide arm reached the highest dose, likely influenced by investigator familiarity and open-label bias.

• No new safety signals were observed for CagriSema.

Interpretation and future directions

• Investigators noted tirzepatide performed unusually well compared to historical data, possibly due to open-label bias and investigator experience.

• Not all patients reached the full dose of CagriSema, suggesting further weight loss potential if optimal dosing is achieved.

• Learnings from REDEFINE 1 and 4 are being incorporated into REDEFINE 11, which aims to better capture CagriSema's full efficacy.

• A phase III trial of high-dose CagriSema is planned for late 2026, and REDEFINE 11 results are expected in the first half of 2027.

• Additional head-to-head studies may be considered after further data review.