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/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.

• All participants and investigators were aware of treatment assignments.

Key efficacy and safety results

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

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

• Using the treatment-regimen estimand, CagriSema achieved 20.2% weight loss versus 23.6% for tirzepatide.

• Both treatments showed similar safety and tolerability profiles, with gastrointestinal events being the most common and generally mild to moderate, diminishing over time.

Interpretation and trial limitations

• Tirzepatide's efficacy in this trial exceeded typical results from previous studies, possibly due to open-label design and investigator familiarity.

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

• Not all CagriSema patients reached the full target dose, suggesting further weight loss potential remains untapped.