REDEFINE 1: CagriSema shows superior weight loss

The trial included 3,417 randomised people with obesity or overweight with one or more comorbidities and a mean baseline body weight of 106.9 kg. The trial achieved its primary endpoint by demonstrating a statistically significant and superior weight loss at week 68 with CagriSema versus placebo.

The REDEFINE 1 trial was based on a flexible protocol, allowing patients to modify their dosing throughout the trial. After 68 weeks, 57.3% of patients treated with CagriSema were on the highest dose compared to 82.5% with cagrilintide 2.4 mg and 70.2% with semaglutide 2.4 mg. When evaluating the effects of treatment if all people adhered to treatment , people treated with CagriSema achieved a superior weight loss of 22.7% after 68 weeks compared to a reduction of 11.8% with cagrilintide 2.4 mg, 16.1% with semaglutide 2.4 mg and 2.3% with placebo alone. In addition, 40.4% of patients who received CagriSema reached a weight loss of 25% or more after 68 weeks, compared to 6.0% with cagrilintide 2.4 mg, 16.2% with semaglutide 2.4 mg, and 0.9% with placebo. When applying the treatment policy estimand , people treated with CagriSema achieved a superior weight loss of 20.4% compared to a reduction of 11.5% with cagrilintide 2.4 mg, 14.9% with semaglutide 2.4 mg and 3.0% with placebo. In the trial, CagriSema, cagrilintide 2.4 mg and semaglutide 2.4 mg appeared to have a safe and well-tolerated profile. The most common adverse events with CagriSema were gastrointestinal, and the vast majority were mild to moderate and diminished over time, consistent with the GLP-1 receptor agonist class.

“We are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide in monotherapy in the REDEFINE 1 trial. This was achieved even though only 57% of patients reached the highest CagriSema dose,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “With the insights obtained from the REDEFINE 1 trial, we plan to further explore the additional weight loss potential of CagriSema.”

The results from the second pivotal phase III trial, REDEFINE 2, in adults with type 2 diabetes and either obesity or overweight are expected during the first half of 2025.

REDEFINE is a phase III clinical development programme with once-weekly subcutaneous CagriSema in obesity. The global clinical trial programme consists of two pivotal phase III trials, which have enrolled approximately 4,600 adults with overweight or obesity. Additional phase 3 trials are ongoing.

REDEFINE 1 – a 68-week efficacy and safety  phase  III t rial of once-weekly CagriSema, cagrilintide 2.4 mg and semaglutide 2.4 mg versus placebo in 3,400 adults with obesity or overweight with one or more comorbidities and without type 2 diabetes.

REDEFINE 2 – a 68-week efficacy and safety phase III trial of once-weekly CagriSema versus placebo in 1,200 adults with type 2 diabetes and either obesity or overweight.

REDEFINE 3 – an event-driven cardiovascular outcomes phase III trial of once-weekly CagriSema versus placebo in 7,000 adults with established cardiovascular disease with or without type 2 diabetes.

REDEFINE 4 – a 72-week efficacy and safety phase III trial of once-weekly CagriSema versus once-weekly tirzepatide 15 mg in 800 adults with obesity.