Novo to advance CagriSema despite missing key endpoint against Lilly in obesity trial

Days after its next-generation anti-obesity drug failed to match the weight-loss results of rival Eli Lilly’s tirzepatide in a closely watched head-to-head trial, Danish drugmaker Novo Nordisk said on Wednesday that it would continue advancing CagriSema, citing its strong weight-loss profile and the large unmet need in obesity.
 
The 84-week REDEFINE 4 Phase 3 study compared to a once-weekly CagriSema (2.4mg cagrilintide and 2.4mg semaglutide) with tirzepatide 15mg in 809 adults with obesity and at least one related health condition. The trial did not meet its primary endpoint of demonstrating non-inferiority to tirzepatide.
Patients taking CagriSema lost 23% of their body weight under the efficacy analysis, compared with 25.5% for tirzepatide. When treatment adherence was factored in, weight loss was 20.2% for CagriSema versus 23.6% for tirzepatide.
 
In a statement on Wednesday, Novo Nordisk said, “In REDEFINE 4, CagriSema (2.4mg/2.4mg) did not meet its primary endpoint when compared to tirzepatide (15mg), meaning it was not deemed ‘non-inferior’ to tirzepatide, in this trial at least. The weight loss, however, was good. People treated with CagriSema over 84 weeks lost 23% of their body weight, which is in line with REDEFINE 1’s 22.7% and at par with the most efficient obesity medicines on the market.”
 
The company further added that given the large unmet need in obesity and CagriSema’s strong weight loss profile, cardiometabolic benefits (heart, liver, kidney) and proven efficacy of semaglutide with more than 49 million patient years of exposure, it is committed to continuing to study CagriSema, which will be the first amylin combination medicine for obesity. We believe in the power of this biology, it said.
 
On future trials, Novo Nordisk said, “We are particularly excited about REDEFINE 11, which has a longer duration than REDEFINE 1 and an optimised trial design that will ensure patients get the full weight-loss benefits of CagriSema.”
 
The company had previously reported 22.7% weight loss in REDEFINE 1, positioning CagriSema among the more effective obesity treatments currently in development. The obesity therapeutics segment has emerged as one of the most commercially significant areas in pharmaceuticals, with analysts estimating the global market could exceed $100 billion annually over the next decade. More than 650 million adults worldwide live with obesity, according to the World Health Organization, creating sustained demand for long-term treatment options.
 
Novo Nordisk’s semaglutide franchise, led by Ozempic and Wegovy, generated more than $30 billion in global sales in 2024. However, Lilly’s tirzepatide has set higher efficacy benchmarks in several trials, intensifying competition between the two companies.
 
CagriSema combines semaglutide, a GLP-1 receptor agonist, with cagrilintide, a long-acting amylin analogue designed to enhance satiety and reduce calorie intake through complementary biological pathways.
CagriSema has already been submitted to the US Food and Drug Administration for weight management based on earlier REDEFINE trials, with a regulatory decision expected by late 2026. Additional data from REDEFINE 11 are anticipated in the first half of 2027, and a higher-dose Phase 3 trial is planned for the second half of 2026.
 
In a recent interview with Business Today, Vikrant Shrotriya, Managing Director, Novo Nordisk India, said the company is deepening its focus on next-generation metabolic therapies as competition intensifies. He described multi-hormone combinations such as GLP-1 and amylin as “the next major leap in metabolic care”, particularly in India, where “obesity and diabetes coexist in nearly 70 per cent of patients”.
 
“Semaglutide has long-term clinical evidence for effective blood sugar control and weight loss, as well as cardiovascular, hepatic and renal benefits,” Shrotriya said. Globally, Novo Nordisk invested more than DKK 60 billion in research and development in 2024 and over DKK 129 billion in production capacity.