CagriSema associated with significant reduction in blood pressure and reduces the proportion of patients at risk of developing heart disease

Post hoc analyses from the phase 3 REDEFINE 1 trial evaluating CagriSema, an investigational injectable combination treatment for adults with overweight or obesity, and its effects on well-known cardiovascular (CV) risk factors, has revealed that systolic blood pressure was reduced by -10.9 mmHg over 68 weeks (versus -8.8 mmHg with semaglutide 2.4 mg and -2.1 mmHg with placebo).

This reduction was seen regardless of BMI (less than versus greater than or equal to 35 kg/m2). In the CagriSema group, nearly 4 out of 10 people who had been on blood pressure-lowering medication were able to cut down or stop this medication during the trial. Exploratory post hoc analyses are hypothesis generating, and further work investigating the clinical validity of these results would be of value.

CagriSema was also associated with a reduction in a key marker of body-wide inflammation – high-sensitivity C-reactive protein (hsCRP) – at week 68, regardless of baseline hsCRP levels. The reduction with CagriSema (–68.9%) was greater than with semaglutide 2.4 mg alone (–55.4%) or placebo (–16.0%). In a mediation analysis, the hsCRP reduction with CagriSema was only partially explained by weight loss, suggesting that the inflammatory effects of CagriSema are not fully weight loss dependent.

REDEFINE 1 was a double-blind, placebo-and active-controlled 68-week efficacy and safety phase 3 trial of once-weekly CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg), cagrilintide 2.4 mg monotherapy and semaglutide 2.4 mg monotherapy versus placebo in 3,417 adults with obesity (BMI ≥30 kg/m2), or overweight (BMI ≥27 kg/m2) with one or more obesity-related comorbidities, and without type 2 diabetes.

Safety data generated in the REDEFINE 1 trial were comparable with the GLP-1 RA class. Overall, discontinuation rates due to adverse events were low, with 6% for CagriSema versus 3.7% for placebo. In REDEFINE 1, adverse events were mainly gastrointestinal (79.6% in the CagriSema group versus 39.9% with placebo), including nausea (55% versus 12.6%), constipation (30.7% versus 11.6%), and vomiting (26.1% versus 4.1%), and were mostly transient and mild-to-moderate in severity.

CagriSema is being investigated by Novo Nordisk as a once-weekly subcutaneous injectable treatment for adults with overweight or obesity (REDEFINE program) and as a treatment for adults with type 2 diabetes (REIMAGINE program). CagriSema is a fixed-dose combination of a long-acting amylin analogue, cagrilintide 2.4 mg, and the GLP-1 receptor agonist, semaglutide 2.4 mg.

CagriSema is not approved in the US or EU.