CagriSema Demonstrates Statistically Significant, Superior Weight Loss Vs Placebo

Novo Nordisk’s newest obesity therapy has demonstrated “statistically significant and superior weight loss” compared to both the individual components and to placebo, according to a company news release.¹

Although the drug fell short of its 25% expected weight loss, results are still promising for people with overweight or obesity. | Image credit: New Africa - stock.adobe.com

The drug, CagriSema, is a once-weekly, fixed-dose combination of cagrilintide 2.4 mg, a long-acting amylin analog, and semaglutide 2.4 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist administered via subcutaneous injection.

Cagrilintide/semaglutide was evaluated in the REDEFINE 1 clinical trial (NCT05567796), which included 3417 adults with overweight or obesity, 1 or more comorbidity, and a mean baseline body weight of 106.9 kg (235.6 lbs).

At the conclusion of the 68-week study period, investigators found that the drug achieved its primary endpoint of statistically significant, superior weight loss. The trial had a flexible protocol, allowing patients to modify their dosing throughout. At the end of the study, 57.3% of participants in the cagrilintide/semaglutide group were on the highest medication dose, compared with 82.5% in the cagrilintide group and 70.2% in the semaglutide group.

When evaluating treatment effects if all individuals adhered to treatment, those who received cagrilintide/semaglutide achieved superior weight loss—22.7%—after 68 weeks vs 11.8% and 16.1% weight loss in the cagrilintide and semaglutide groups, respectively, and vs 2.3% in the placebo group. Additionally, investigators found that 40.4% of patients in the cagrilintide/semaglutide group achieved weight loss of 25% or more at 68 weeks (6%, 16.2% and 0.2% vs cagrilintide, semaglutide, and placebo, respectively).

READ MORE: Pfizer Advances Oral GLP-1 Development as the Race for Second-Gen Obesity Therapies Continues

Results also indicated that cagrilintide/semaglutide was safe and well-tolerated; the most common adverse events were mild to moderate gastrointestinal that diminished over time, which are consistent with other drugs in the GLP-1 receptor agonist class.

“We are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide in monotherapy in the REDEFINE 1 trial,” said Martin Holst Lange, executive vice president of development at Novo Nordisk. “This was achieved even though only 57% of patients reached the highest CagriSema dose.”

Using these insights, the company plans to continue exploring “the additional weight loss potential” of the drug, Lange added.

Although cagrilintide/semaglutide fell short of its targeted 25% weight loss,² the results of REDEFINE 1 are still promising for patients with obesity. Earlier medications led to less overall weight loss, required daily pills or injections, and were associated with adverse effects that could include headache, high blood pressure, rapid or irregular heart rate, and altered taste, among others.³

Novo Nordisk expects results from a second pivotal phase 3 trial, REDEFINE 2—evaluating cagrilintide/semaglutide in adults with overweight or obesity and type 2 diabetes—in the first half of 2025. Through the REIMAGINE program, the manufacturer is evaluating the drug’s use in adults with type 2 diabetes.

READ MORE: Obesity Management Resource Center

References

1. Novo Nordisk A/S: CagriSema demonstrates superior weight loss in adults with obesity or overweight in the REDEFINE 1 trial. News release. Novo Nordisk. December 20, 2024. Accessed December 20, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915082

2. Fick M. Novo Nordisk affirms 25% weight-loss expectation for experimental drug CagriSema. Reuters. November 6, 2024. Accessed December 20, 2024. https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-its-experimental-drug-cagrisema-has-similar-side-effects-2024-11-06/

3. Top weight loss medications. Obesity Medicine Association. January 26, 2024. Accessed December 20, 2024. https://obesitymedicine.org/blog/weight-loss-medications/