Cagrilintide Demonstrates Promising Results as Monotherapy for Obesity Management

In the phase 3, double-blind, placebo-and active-controlled 68-week efficacy and safety REDEFINE 1 trial (NCT05567796), cagrilintide (Novo Nordisk) 2.4 mg monotherapy—a long-acting amylin analogue that mimics the naturally occurring hormone amylin—demonstrated clinically meaningful weight loss for adults with obesity or overweight compared with placebo. These findings mark the first and only phase 3 clinical trial results evaluating an investigational long-acting amylin analogue used alone for the treatment of obesity.^1,2

“Our current and future therapies aim to help people with obesity achieve meaningful weight loss and broader health benefits. With the global scale of obesity, further scientific innovation and therapy options are needed to meet every individual's needs and preferences,” Martin Holst Lange, chief scientific officer and executive vice president of Research & Development at Novo Nordisk, said in a news release.¹

Cagrilintide’s Role in Weight Management

As a long-acting amylin analogue, cagrilintide mimics the naturally occurring hormone amylin and works differently than other approved glucagon-like peptide-1s (GLP-1) for weight loss. The drug is intended to be used alone or in combination with semaglutide (CagriSema; Novo Nordisk) for weight loss and improved glycemic control.¹

REDEFINE-1 Overview and Results

A total of 3417 adults with obesity or overweight with at least 1 or more comorbidities and without type 2 diabetes were included in the phase 3 trial. The initial trial assessed the use of once-weekly cagrilintide 2.4 mg and semaglutide 2.4 mg, cagrilintide 2.4 mg monotherapy, and semaglutide 2.4 mg monotherapy versus placebo. In this post hoc analysis, researchers assessed the efficacy and safety of cagrilintide 2.4 mg monotherapy compared with a placebo for a 68-week period.¹

The results demonstrated that cagrilintide displayed clinically meaningful weight loss, with an average body weight reduction of 11.8% compared with 2.3% with placebo after 68 weeks, if all patients adhered to treatment. Further findings revealed that 31.6% of patients receiving cagrilintide achieved greater than 15% weight loss, compared with 4.7% of patients receiving placebo. However, the treatment effect, regardless of adherence, demonstrated an average weight loss of 11.5% in cagrilintide patients, compared with 3.0% using placebo. Additionally, 31.0% of those treated with cagrilintide achieved at least 15% weight loss versus only 5.2% in the placebo group.¹

“These data highlight the exciting potential of cagrilintide to offer an alternative approach for people to lose weight, achieve health-related outcomes and manage their obesity, including a favorable tolerability profile,” Timothy Garvey, MD, lead investigator, professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham, said in the news release. “Like other chronic diseases, we need a range of treatment options to address the individual needs of people with obesity, such as their own specific response to treatment.”¹

The most common adverse effects were gastrointestinal, including nausea, vomiting, diarrhea, and constipation that were mild to moderate in severity. Despite this, cagrilintide was well tolerated.¹

“In our clinical trials, cagrilintide has provided substantial weight loss, in a distinct manner compared to approved obesity medications, and appears well-tolerated. We’re excited that these data, the first phase 3 data of a next-generation amylin therapy, show promise and we look forward to further investigating cagrilintide’s potential in the dedicated phase 3 RENEW program,” Holst said in the news release.¹

REFERENCES

1. Novo Nordisk presents phase 3 data for next-generation amylin cagrilintide, leading to advancement into dedicated clinical programme. Novo Nordisk. News release. September 16, 2025. Accessed October 7, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916427

2. A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight (REDEFINE 1). National Library of Medicine. https://clinicaltrials.gov/study/NCT05567796