Novo Nordisk’s CagriSema Achieves 22.7% Weight Loss In Obesity Trial, Shows Potential As Next-Gen Dual Hormone Therapy

Novo Nordisk has announced robust results from its Phase 3 REDEFINE 1 trial, evaluating the investigational weight loss therapy CagriSema in adults with obesity or overweight and a related medical condition but without diabetes. Published in The New England Journal of Medicine and presented at the ADA’s 85th Scientific Sessions, the findings show that CagriSema, an innovative combination of semaglutide (a GLP-1 receptor agonist) and cagrilintide (an amylin analogue) achieved significant and clinically meaningful weight loss when paired with lifestyle interventions over a 68-week period.

“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. These results reinforce our confidence in CagriSema, and we continue to study the potential of this combination through the REDEFINE trials,” said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. 

Patients treated with CagriSema experienced a 22.7% mean reduction in body weight compared to just 2.3% in the placebo group when treatment adherence was assumed. When evaluated regardless of adherence, the results still showed a 20.4% weight loss with CagriSema vs. 3.0% with placebo. Remarkably, more than half of those treated crossed the BMI threshold to fall below the obesity range (BMI < 30). Furthermore, nearly 35% of participants achieved ≥25% body weight reduction, and approximately 19% lost over 30% of their body weight.

"In REDEFINE 1, CagriSema provided weight loss in the highest range of efficacy observed with existing weight loss interventions.Investigators were allowed some flexibility in dose adjustments to balance efficacy and safety, but regardless of dose adjustments participants lost significant weight. These findings are relatable to clinical practice, where dosing is often adjusted based on individual needs and clinical judgement,” said lead investigator Timothy Garvey, MD, professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham. 

CagriSema was generally well tolerated, with adverse events consistent with the GLP-1 RA drug class, mostly mild-to-moderate gastrointestinal symptoms. Discontinuation due to side effects was relatively low (6% vs. 3.7% for placebo). Building on this success, Novo Nordisk has already initiated the REDEFINE 11 study, which aims to explore the long-term efficacy and safety of the same dose of CagriSema in a longer-duration trial.