CagriSema Phase 3 Update: Weight Loss of Nearly 16% Seen in REDEFINE 2 Trial
CagriSema proved superior to placebo in the pivotal phase 3 trial but as in the earlier REDEFINE 1 study fell short of the 25% or greater reduction Novo Nordisk projected.
Novo Nordisk’s investigational combination therapy, CagriSema, achieved significant weight loss in adults with obesity or overweight and type 2 diabetes (T2D), according to results from the phase 3 REDEFINE 2 trial, announced on March 10, 2025.1 Over the 68-week study period, participants treated with CagriSema experienced an average weight reduction of 15.7%, compared to 3.1% with placebo, when assessing only those who adhered to treatment. When applying a broader treatment policy analysis, weight loss was 13.7% with CagriSema vs 3.4% with placebo.
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The trial also met its co-primary endpoint of weight loss of at least 5% at 68 weeks, with 89.7% of participants on CagriSema reaching the goal vs 30.3% in the placebo group.
“The REDEFINE 2 results confirmed the superior efficacy of CagriSema in people with overweight or obesity and type 2 diabetes,” Martin Holst Lange, executive vice president for development at Novo Nordisk, said in a company statement. “We look forward to bringing this second pivotal trial to regulatory authorities with the aim of making this next-generation therapy available to the millions of patients in need.”
CagriSema is a novel once-weekly subcutaneous fixed-dose combination of the long-acting amylin analogue cagrilintide (2.4 mg) and the glucagon like peptide-1 receptor agonist semaglutide (2.4 mg). The unique pairing of peptides combines attributes that support weight reduction including slowed gastric emptying, reduced secretion of glucagon, and increased satiety.
REDEFINE 2 enrolled 1,206 adults with a mean baseline body weight of 102 kg. The trial utilized a flexible dosing protocol, allowing participants to modify their dosing throughout the trial, according to Novo Nordisk. After 68 weeks, 61.9% of CagriSema-treated participants were receiving the highest dose.
The REDEFINE 2 safety data indicated that CagriSema was well tolerated. The most common adverse events were gastrointestinal-related, were primarily mild to moderate, and diminished over time, consistent with the known safety profile of GLP-1 receptor agonists.
In the previously reported phase 3 REDEFINE 1 trial, the combination met its primary endpoint, a statistically significant and superior weight loss of 22.7% after 68 weeks of treatment compared with placebo in a cohort of adults with obesity or with overweight and without T2D.2 Although meeting this endpoint, however, the study's 22.7% reduction in weight across CagriSema dosing fell short of company and analyst expectations, which were set at 25% or more, according to industry outlets.2
At the time of the announcement of the results, Lange said the company was "encouraged" by the weight reduction superiority of CagriSema compared to placebo and to both semaglutide and cagrilintide monotherapy.2 Just slightly more than half, 57%, of REDEFIND 1 participants reached the highest dose of CagriSema in the study, another less than favorable outcome that Novo Nordisk attributed to the study's flexible dosing protocol.2
Novo Nordisk expects to file for regulatory approval of CagriSema in the first quarter of 2026. Additional detailed results from REDEFINE 1 and REDEFINE 2 will be presented at an upcoming scientific conference in 2025, the company stated in the announcement.
The Phase 3 REDEFINE Program
REDEFINE is a phase 3 clinical development program with once-weekly subcutaneous CagriSema in obesity. The global clinical trial program consists of 2 pivotal phase 3 trials, which have enrolled approximately 4,600 adults with overweight or obesity. The full phase 3 trial program includes:
- REDEFINE 1 – a 68-week efficacy and safety phase 3 trial of once-weekly CagriSema, cagrilintide 2.4 mg and semaglutide 2.4 mg versus placebo in 3,417 adults with obesity or overweight with one or more comorbidities and without type 2 diabetes.
- REDEFINE 2 – a 68-week efficacy and safety phase 3 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 3 trial of once-weekly CagriSema versus placebo in 7,000 adults with established cardiovascular disease with or without T2D.
- REDEFINE 4 – an 84-week efficacy and safety phase 3 trial of once-weekly CagriSema versus once-weekly tirzepatide 15 mg in 800 adults with obesity.
