CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1

Background: Fixed-dose combination of semaglutide/cagrilintide (CagriSema 2.4 mg/2.4 mg) has demonstrated significant and clinically relevant body weight reductions in adults with overweight or obesity compared with placebo. Methods: The phase 3a, 68-week REDEFINE 1 trial randomized adults without diabetes with body mass index ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related complication, to once-weekly CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, plus lifestyle intervention. Secondary and post hoc analyses evaluated the antihypertensive effect from REDEFINE 1, focusing on CagriSema and placebo groups, by subgroup/category, including baseline body mass index, the presence of hypertension or resistant hypertension at baseline, and concomitant changes in the use of antihypertensive medications. Results: Overall, 3417 participants underwent randomization; CagriSema: n=2108, semaglutide: n=302, cagrilintide: n=302, and placebo: n=705. Changes from baseline to week 68 in blood pressure (BP) were greater with CagriSema versus placebo (systolic BP: -10.9 versus -2.8 mm Hg; diastolic BP: -5.4 versus -1.7 mm Hg, respectively). The proportion of participants reaching BP targets at week 68 was 63.0% and 32.0% for CagriSema and placebo, respectively. The proportion of participants with resistant hypertension at baseline (n=167) that reached BP targets at week 68 was 42.0% and 29.3% for CagriSema and placebo, respectively (odds ratio, 1.7 [95% CI, 0.7-4.4]). Among participants who used antihypertensive medication during the study, 39.6% in the CagriSema group decreased or stopped treatment from week 0 to week 68 versus 18.8% with placebo. Conclusions: CagriSema presents clinically relevant reductions in BP across a wide range of participant subgroups, including those with resistant hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05567796.