Novo Nordisk CagriSema Results Fall Short

Novo Nordisk A/S (NVO) reported on Feb. 23, 2026 that its experimental once-weekly combination, CagriSema, failed to meet the REDEFINE 4 trial’s pre-specified non-inferiority goal against tirzepatide. The company released these topline results ahead of further data and regulatory milestones.

Head-to-Head Trial Results and Safety Profile

REDEFINE 4 was an 84-week, open-label phase 3 trial comparing CagriSema with tirzepatide 15 mg in 809 adults with obesity and comorbidities. Participants had a mean baseline weight of 114.2 kg. The company reported outcomes using two efficacy measures: the efficacy estimand, a per-protocol analysis regardless of dose changes, and the treatment-regimen estimand, which reflects real-world adherence.

Under the efficacy estimand, CagriSema achieved 23.0% weight loss at 84 weeks, compared with 25.5% for tirzepatide. The treatment-regimen estimand showed 20.2% weight loss for CagriSema versus 23.6% for tirzepatide. The trial did not meet its primary endpoint of non-inferiority, raising questions about CagriSema’s competitive positioning against an established glucose- and weight-loss agent.

CagriSema combines the amylin analogue cagrilintide and the GLP-1 receptor agonist semaglutide at fixed doses of 2.4 mg each, administered once weekly by subcutaneous injection. Gastrointestinal adverse events were the most common side effects, generally mild to moderate and diminishing over time, consistent with the GLP-1 receptor agonist class.

Martin Holst Lange, Novo Nordisk’s executive vice president of research and development and chief scientific officer, said, "We are pleased with the weight loss of 23% for CagriSema in this open-label trial."

Regulatory and Development Outlook

Novo Nordisk submitted a U.S. New Drug Application for CagriSema in December 2025 based on the REDEFINE 1 and 2 pivotal studies. The U.S. Food and Drug Administration’s decision is expected in late 2026. The REDEFINE 4 topline results provide fresh comparative data but do not affect the ongoing regulatory review.

The company plans to start a higher-dose phase 3 program testing CagriSema 2.4/7.2 mg in the second half of 2026. It also expects data from REDEFINE 11, a placebo-controlled study with an 80-week primary period plus extension, in the first half of 2027. Novo Nordisk scheduled an investor conference call to discuss the topline announcement. The REDEFINE 11 readout will be the next major data milestone and could influence regulatory and clinical assessments.