CagriSema Reduces SBP by 10.9 mmHg in Post Hoc Analysis of REDEFINE 1 Trial

Novo Nordisk's investigational obesity treatment CagriSema reduced systolic blood pressure by 10.9 mmHg over 68 weeks in adults with overweight or obesity, according to findings of a post hoc analysis of the phase 3 REDEFINE 1 trial presented during this week's ObesityWeek meeting in Atlanta.¹

The results of the the cardiovascular risk reduction analysis were publisehd simultaneously in the journal Hypertension on November 6, 2025, according to a company statement.¹

Reduced Need for Antihypertensives

The combination treatment, which pairs the long-acting amylin analogue cagrilintide 2.4 mg with GLP-1 receptor agonist semaglutide 2.4 mg in a once-weekly subcutaneous injection, produced greater blood pressure reductions than semaglutide 2.4 mg alone (–8.8 mmHg) or placebo (–2.1 mmHg). The blood pressure effect remained consistent across categories of body mass index categories, and nearly 40% of participants taking antihypertensive medications reduced or discontinued their blood pressure drugs during the trial. Importantly, in participants identified as having resistant hypertension at baseline CagriSema achieved greater BP reductions than placebo for SBP (–8.6 vs –4.9 mm Hg) and DBP (–3.1 vs –0.9 mm Hg), according to the results.

Independent Anti-inflammatory Effect

CagriSema also reduced high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation linked to cardiovascular risk, by 68.9% at week 68, compared with 55.4% for semaglutide alone and 16.0% for placebo, according to the study abstract. A mediation analysis found that weight loss only partially explained the hsCRP reduction, suggesting an anti-inflammatory effect that extends beyond the medication's impact on body weight.

Additional analysis showed that fewer participants taking CagriSema fell into the intermediate-to-high risk category for developing atherosclerotic cardiovascular disease (ASCVD) within 10 years compared with other treatment groups.

"We're very excited by the results of these analyses of CagriSema, which show promising results of combining cagrilintide with the proven significant effects of semaglutide on CV health," Martin Holst Lange, chief scientific officer and executive vice president of R&D at Novo Nordisk, said in the statement. "People living with obesity have treatment goals that often include both losing weight and improving overall health, he continued, goals that support the company's ongoing research into pluripotent therapies.

Fewer participants taking CagriSema fell into the intermediate-to-high risk category for developing ASCVD within 10 years compared with other treatment groups.

"The CagriSema data presented at ObesityWeek are very encouraging regarding the effects on well-known CV risk factors like high blood pressure, a strong signal that warrants further investigation," first author Subodh Verma, MD, PhD, Canada Research Chair in Cardiovascular Surgery at the University of Toronto, said in a statement. "If we can lower inflammation, bring blood pressure to more normal levels, and help people lose weight at the same time, there's potential for holistic improvement in overall health."

The REDEFINE 1 Trial

The REDEFINE 1 trial enrolled 3,417 adults with obesity (BMI 30 kg/m² or greater) or overweight (BMI 27 kg/m² or greater) with one or more obesity-related comorbidities but without type 2 diabetes. The 68-week double-blind study compared the comination CagriSema, cagrilintide 2.4 mg monotherapy, and semaglutide 2.4 mg monotherapy against placebo.

The CagriSema safety profile was consistent with the GLP-1 receptor agonist class. Adverse-event–related discontinuation occurred in 6% of CagriSema-treated participants vs 3.7% treated with placebo. GI events were more common with CagriSema (79.6% vs 39.9%), chiefly nausea (55% vs 12.6%), constipation (30.7% vs 11.6%), and vomiting (26.1% vs 4.1%). Most events were transient and mild to moderate.”

Verma and colleagues emphasized that these post hoc analyses are hypothesis-generating and that further studies are needed to confirm the clinical relevance of the findings. Novo Nordisk is currently conducting REDEFINE 3, a dedicated trial assessing CagriSema’s impact on cardiovascular outcomes in patients with established cardiovascular disease, with or without type 2 diabetes.

CagriSema, a combination of a long-acting amylin analogue and a GLP-1 receptor agonist, is under investigation in the REDEFINE program for adults with overweight or obesity and the REIMAGINE program for adults with type 2 diabetes. The drug has not yet been approved in the United States or European Union.