Key Takeaways
- CagriSema delivers significant weight loss: In the REDEFINE 1 trial, Novo Nordisk’s CagriSema achieved a 22.7% mean weight reduction in adults with obesity or overweight without diabetes.
- Over half reached non-obese body mass index (BMI): 50.7% of CagriSema-treated participants reached a BMI below 30, compared to just 10.2% in the placebo group.
- Investors weigh CagriSema vs. tirzepatide: Despite strong results, market skepticism remains due to CagriSema falling short of the anticipated 25% weight loss and stiff competition from Eli Lilly’s tirzepatide.
Results from the Phase III REDEFINE 1 trial show that Novo Nordisk’s investigational combination therapy CagriSema (2.4 mg semaglutide/2.4 mg cagrilintide) significantly outperformed placebo in adults with overweight or obesity and at least one weight-related medical condition, but without diabetes. The data, along with findings from the Phase III REDEFINE 2 trial, were presented at the American Diabetes Association’s 85th Scientific Sessions and published in The New England Journal of Medicine.1
Can CagriSema Challenge Existing Leaders in Obesity Treatment?
“In REDEFINE 1, participants saw significant and clinically meaningful weight loss under a protocol that allowed investigators to maintain patients on a submaximal dose if deemed best for the patient. We also witnessed low, single-digit discontinuation rates due to adverse events in both REDEFINE 1 and 2,” said Martin Holst Lange, EVP, head of development, Novo Nordisk, in a press release. “These results reinforce our confidence in CagriSema, and we continue to study the potential of this combination through the REDEFINE trials.”
REDEFINE 1 Trial Design and Endpoints
- The double-blind, placebo- and active-controlled 68-week REDEFINE 1 trial evaluated the efficacy and safety of CagriSema compared to placebo in 3,417 adults with obesity or overweight with one or more comorbidities and without type 2 diabetes.
- The dual primary endpoints of the trial were the percentage change in body weight from baseline to week 68 and the proportion of participants achieving at least 5% weight loss at week 68.
- Secondary endpoints included the proportion of patients achieving ≥10%, ≥15%, ≥20%, ≥25%, and ≥30% body weight reduction at week 68, the proportion of patients reaching a body mass index (BMI) below the obesity threshold and change in body composition.
Key Efficacy Findings
- CagriSema demonstrated a 22.7% mean weight reduction at 68 weeks.
- Additionally, 50.7% of CagriSema-treated participants reached a non-obese BMI compared to 10.2% in the placebo group.
- Further, 40.4% of patients in the treatment group achieved a body weight reduction of ≥25%.
- Around 23.1% lost ≥30% of their body weight. Using the treatment policy estimand, 34.7% of participants on CagriSema achieved ≥25% weight loss, and 19.3% achieved ≥30%.
CagriSemaSafety Profile and Adverse Events
- Safety data from the REDEFINE 1 and REDEFINE 2 trials were reported to be comparable with the GLP-1 receptor agonist class.
- Approximately 6% of patients discontinued treatment due to adverse events (AEs) compared to 3.7%. in the placebo group.
- AEs were mainly gastrointestinal, and included nausea, constipation, vomiting, and were mostly transient and mild-to-moderate in severity.1
Market Reaction and Competitive Landscape
The results come amid investor scrutiny after Novo Nordisk’s US-listed shares fell 7% in premarket trading, as CagriSema did not meet the 25% weight-loss target previously suggested by company leadership. Citi Research analyst Paul Lejuez told Barron’s that the market remains cautious, particularly given recent momentum behind Eli Lilly’s tirzepatide, which is already approved for both weight management and type 2 diabetes. While CagriSema may show slightly greater efficacy—by approximately 2% to 3%—Lejuez said this is unlikely to support a narrative that it could replace tirzepatide.2
