Jul 09, 2025
At the 85th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, Novo Nordisk unveiled pivotal Phase IIIa results from its REDEFINE clinical program, reinforcing the potential of CagriSema—a once-weekly co-formulation of cagrilintide (amylin analogue) and semaglutide (GLP-1 receptor agonist)—as a transformative therapy for individuals with obesity, with and without T2D.
REDEFINING CagriSema
REDEFINE 1, a global, double-blind, 68-week trial in 3,417 adults with overweight or obesity (but without diabetes), demonstrated that CagriSema achieved an average body weight reduction of 20.4%, compared to just 3.0% with placebo, translating to a treatment difference of −17.3 percentage points (p<0.001). These results put CagriSema at the top end of efficacy among current non-surgical weight loss interventions. Notably, over 50% of CagriSema-treated participants reached a BMI below the obesity threshold, compared to just 10.2% on placebo. A significantly higher proportion of patients on CagriSema also achieved ≥5%, 20%, 25%, and even 30% weight reduction. Gastrointestinal events—mainly mild to moderate and transient—were the most common adverse effects, reported in 79.6% of patients on CagriSema vs. 39.9% on placebo.
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In REDEFINE 2, which included 1,206 adults with T2D, CagriSema maintained strong efficacy, achieving a mean weight loss of 13.7% vs. 3.4% with placebo, and a treatment difference of −10.4 percentage points (p<0.001). Importantly, 73.5% of patients reached an HbA1c of ≤6.5%, compared to just 15.9% on placebo, demonstrating dual efficacy in weight and glycemic control. The consistency of outcomes across both nondiabetic and diabetic populations underscores the versatility of CagriSema as a next-generation metabolic therapy.
Novo Nordisk’s REDEFINE program, which now includes the newly launched REDEFINE 11 trial, is designed to further optimize CagriSema’s positioning across obesity and diabetes care by exploring longer treatment durations and alternative protocol designs.
KOL Views
From a public health standpoint, CagriSema has the potential to transform the landscape of obesity and diabetes care, especially as obesity rates continue to rise globally and effective, sustainable interventions remain limited. – Expert Opinion
We have got very powerful agents that are able to lower HbA1c and weight in patients with T2D. These results are amongst the best we have ever seen. This is the second dual-approach agent after tirzepatide (MOUNJARO/ZEPBOUND, Eli Lilly) to show really good results. What sets CagriSema apart is the mechanism of action, with the amylin analog. In the continuous glucose monitoring subgroup, we saw that it was very effective from a glycemic control perspective. – Expert Opinion
Conclusion
CagriSema, Novo Nordisk’s dual-hormone combination of semaglutide (GLP-1 RA) and cagrilintide (amylin analogue), demonstrated robust efficacy in the REDEFINE 1 and 2 trials, achieving up to 20.4% mean weight loss in people without diabetes and 13.7% in those with T2D—outperforming GLP-1 monotherapy. Its favorable tolerability profile and low discontinuation rates further strengthen its clinical appeal. However, despite these results, Novo Nordisk’s shares declined post-announcement, as investors had anticipated even stronger outcomes, particularly in the T2D cohort, where the efficacy lagged behind emerging triple agonists like retatrutide. While the data fell short of market hype, CagriSema’s balanced profile combining meaningful efficacy with safety positions it as a potential option for long-term obesity and T2D management, especially as Novo expands the REDEFINE program with ongoing safety studies.
Article in PDF
Jul 09, 2025
At the 85th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, Novo Nordisk unveiled pivotal Phase IIIa results from its REDEFINE clinical program, reinforcing the potential of CagriSema—a once-weekly co-formulation of cagrilintide (amylin analogue) and semaglutide (GLP-1 receptor agonist)—as a transformative therapy for individuals with obesity, with and without T2D.
REDEFINING CagriSema
REDEFINE 1, a global, double-blind, 68-week trial in 3,417 adults with overweight or obesity (but without diabetes), demonstrated that CagriSema achieved an average body weight reduction of 20.4%, compared to just 3.0% with placebo, translating to a treatment difference of −17.3 percentage points (p<0.001). These results put CagriSema at the top end of efficacy among current non-surgical weight loss interventions. Notably, over 50% of CagriSema-treated participants reached a BMI below the obesity threshold, compared to just 10.2% on placebo. A significantly higher proportion of patients on CagriSema also achieved ≥5%, 20%, 25%, and even 30% weight reduction. Gastrointestinal events—mainly mild to moderate and transient—were the most common adverse effects, reported in 79.6% of patients on CagriSema vs. 39.9% on placebo.
In REDEFINE 2, which included 1,206 adults with T2D, CagriSema maintained strong efficacy, achieving a mean weight loss of 13.7% vs. 3.4% with placebo, and a treatment difference of −10.4 percentage points (p<0.001). Importantly, 73.5% of patients reached an HbA1c of ≤6.5%, compared to just 15.9% on placebo, demonstrating dual efficacy in weight and glycemic control. The consistency of outcomes across both nondiabetic and diabetic populations underscores the versatility of CagriSema as a next-generation metabolic therapy.
Novo Nordisk’s REDEFINE program, which now includes the newly launched REDEFINE 11 trial, is designed to further optimize CagriSema’s positioning across obesity and diabetes care by exploring longer treatment durations and alternative protocol designs.
KOL Views
From a public health standpoint, CagriSema has the potential to transform the landscape of obesity and diabetes care, especially as obesity rates continue to rise globally and effective, sustainable interventions remain limited. – Expert Opinion
We have got very powerful agents that are able to lower HbA1c and weight in patients with T2D. These results are amongst the best we have ever seen. This is the second dual-approach agent after tirzepatide (MOUNJARO/ZEPBOUND, Eli Lilly) to show really good results. What sets CagriSema apart is the mechanism of action, with the amylin analog. In the continuous glucose monitoring subgroup, we saw that it was very effective from a glycemic control perspective. – Expert Opinion
Conclusion
CagriSema, Novo Nordisk’s dual-hormone combination of semaglutide (GLP-1 RA) and cagrilintide (amylin analogue), demonstrated robust efficacy in the REDEFINE 1 and 2 trials, achieving up to 20.4% mean weight loss in people without diabetes and 13.7% in those with T2D—outperforming GLP-1 monotherapy. Its favorable tolerability profile and low discontinuation rates further strengthen its clinical appeal. However, despite these results, Novo Nordisk’s shares declined post-announcement, as investors had anticipated even stronger outcomes, particularly in the T2D cohort, where the efficacy lagged behind emerging triple agonists like retatrutide. While the data fell short of market hype, CagriSema’s balanced profile combining meaningful efficacy with safety positions it as a potential option for long-term obesity and T2D management, especially as Novo expands the REDEFINE program with ongoing safety studies.
