Subcutaneous Cagrilintide, Semaglutide Shows Significant Weight Loss in Type 2 Diabetes Trial

New study findings announced positive results from the phase 3 REDEFINE 2 trial that assessed once-weekly subcutaneous cagrilintide/semaglutide (CagriSema; Novo Nordisk) among individuals with obesity or overweight and type 2 diabetes. The trial met its primary end point of statistically significant and superior weight loss at week 68 with cagrilintide/semaglutide compared to placebo.¹

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“The REDEFINE 2 results confirmed the superior efficacy of CagriSema in people with overweight or obesity and type 2 diabetes," Martin Holst Lange, executive vice president for development at Novo Nordisk, said in a news release.¹

Overweight and obesity are major risk factors for developing type 2 diabetes. According to the Obesity Action Coalition, the prevalence of type 2 diabetes is 3 to 7 times higher among individuals with obesity compared with normal-weight adults. Additionally, the risk is 20 times higher among individuals with a body mass index (BMI) greater than 35 kg/m2.²

Weight loss is crucial for individuals with excess weight or obesity, especially those with type 2 diabetes. The disease usually starts with insulin resistance, which occurs when cells do not use insulin properly. The exact cause of insulin resistance remains unclear, but obesity and inactivity are known to exacerbate it.²

Achieving a moderate and sustained weight loss of 5% to 10% can significantly improve insulin function, lower fasting glucose levels, and decrease medication dependence. While lifestyle changes involving diet, exercise, and behavioral adjustments are effective, medication or surgery might be necessary in some cases.²

CagriSema could offer further treatment for this patient population as a fixed-dose combination of long-acting amylin analogue, cagrilintide 2.4 mg, and semaglutide 2.4 mg. Both medications are indicated to encourage weight loss by decreasing hunger and increasing the feeling of fullness. Its treatment is being assessed in the REDEFINE program.¹

The REDEFINE 2 study included a total of 1200 adults with type 2 diabetes and either obesity or overweight, with a 68-week efficacy and safety profile. The study authors noted that the trial was based on a flexible protocol, which allowed patients to adjust their dosing throughout the study. Among the 1200 individuals included in the study, 61.9% were on the highest dose of cagrilintide/semaglutide.¹

The results demonstrated that after 68 weeks, patients adhering to cagrilintide/semaglutide treatment experienced a 15.7% weight loss, significantly higher than the 3.1% loss observed with placebo. Notably, 89.7% of cagrilintide/semaglutide patients achieved a 5% or greater weight loss, a coprimary end point, compared to only 30.3% of those on placebo.¹

Further results demonstrated that when considering all treated individuals, regardless of adherence, cagrilintide/semaglutide resulted in a 13.7% weight loss, still significantly greater than the 3.4% loss with placebo.¹

Additionally, cagrilintide/semaglutide had a well-tolerated safety profile with mild to moderate gastrointestinal adverse events. However, the adverse events diminished over time.¹

“We look forward to bringing this second pivotal trial to regulatory authorities with the aim of making this next-generation therapy available to the millions of patients in need.” Lange said in a news release.¹

REFERENCES

Novo Nordisk A/S: CagriSema demonstrates superior weight loss in adults with obesity or overweight and type 2 diabetes in the REDEFINE 2 trial. Novo Nordisk. News release. Published March 10, 2025. Accessed March 11, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915294

Obesity Action Coalition. Obesity and Type 2 Diabetes. Accessed March 11, 2025. https://www.obesityaction.org/resources/obesity-and-type-2-diabetes/#:~:text=At%20all%20ages%2C%20the%20risk,be%20associated%20with%20insulin%20resistance