At a Glance
- REDEFINE 4 enrolled 809 people with obesity and comorbidities in an 84-week open-label trial comparing CagriSema to tirzepatide 15 mg.
- CagriSema achieved 23.0% weight loss after 84 weeks on the if-all-adhere estimand compared to 25.5% with tirzepatide.
- CagriSema demonstrated a safe and well-tolerated profile with mostly mild-to-moderate gastrointestinal adverse events.
- CagriSema for weight management was submitted to the US FDA in December 2025 with a decision anticipated by late 2026.
Written By: Pharmacally Medical News Desk
Novo Nordisk released headline results from its REDEFINE 4 phase 3 trial (NCT06131437) on February 23, 2026, pitting its investigational obesity drug CagriSema against Eli Lilly’s tirzepatide. This open-label, 84-week study enrolled 809 adults with obesity and comorbidities, starting at a mean body weight of 114.2 kg.
Both drugs were given once-weekly via subcutaneous injection: CagriSema as a fixed-dose combo of cagrilintide 2.4 mg (an amylin analog) and semaglutide 2.4 mg (a GLP-1 agonist), versus tirzepatide 15 mg.
Key Trial Results
CagriSema delivered solid weight loss, but not enough to meet the primary endpoint of non-inferiority versus tirzepatide.
- If-all-adhere estimand (assuming perfect adherence): 23.0% weight loss with CagriSema vs. 25.5% with tirzepatide.
- Treatment-regimen estimand (real-world adherence): 20.2% vs. 23.6%.
The open-label design where participants and investigators knew the treatments may have influenced adherence and outcomes. Still, Novo executives highlighted CagriSema’s 23% loss as promising, crediting cagrilintide’s additive effects on top of semaglutide for reducing hunger and boosting satiety beyond GLP-1 alone.
Safety aligned with expectations: Gastrointestinal issues dominated for CagriSema, mostly mild-to-moderate and fading over time, mirroring GLP-1 class effects.
Martin Holst Lange, Novo Nordisk’s EVP of R&D and Chief Scientific Officer, emphasized CagriSema’s potential as the first GLP-1/amylin combo to market. “Cagrilintide adds to semaglutide’s benefits, offering superior weight loss to GLP-1 alone,” he said. Novo remains committed to obesity innovation, including CagriSema and zenagamtide.
Regulatory momentum continues: FDA submission for weight management (based on REDEFINE 1 and 2) occurred in December 2025, with a decision expected late 2026. Upcoming milestones include REDEFINE 11 data in H1 2027 and a higher-dose (2.4/7.2 mg) phase 3 start in H2 2026.
Broader REDEFINE Program Context
REDEFINE spans multiple phase 3 trials in 4,600 adults with overweight/obesity, testing CagriSema 2.4/2.4 mg (and variants) against placebo:
Trial | Duration | Focus | Participants |
68 weeks | vs. placebo/components | 3,417 (no T2D) | |
68 weeks | vs. placebo | 1,206 (T2D) | |
REDEFINE 3 | Event-driven | Cardiovascular outcomes | 7,000 (CVD ± T2D) |
REDEFINE 8 | 104 weeks | Body comp/maintenance | 400 |
REDEFINE 9 | 68 weeks | Lower doses | 300 |
REDEFINE 11 | 80 weeks | Full potential/maintenance | 600 |
CagriSema is also in the REIMAGINE program for type 2 diabetes.
This trial underscores the competitive obesity market, where incremental gains matter. Despite missing the endpoint, CagriSema’s profile keeps it in the race.
References
Novo Nordisk A/S: CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trials in people with obesity, the primary endpoint was not achieved, 23 February 2026, News Details
A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight, ClinicalTrials.gov ID NCT06131437, https://clinicaltrials.gov/study/NCT06131437