Semaglutide for the treatment of resistant hypertension

Abstract Background Treatment options for resistant hypertension (RH) are often limited by medication intolerance and adverse effects. Novel approaches to treatment are required. The disease of obesity affects 70% of patients with RH. Purpose To determine if a weight centric approach using semaglutide improved BP control in patients with RH. Methods Individual participant data from three randomised placebo-controlled trials (STEP 1, 3 and 4) examining the effect of semaglutide 2.4mg on body weight over 68 weeks were included. Participants on >4 anti-hypertensive medications or those with systolic BP (SBP) >130mmHg at baseline and 3 anti-hypertensive medications including a diuretic were considered to have RH. Firstly, the change in SBP comparing those on semaglutide to placebo was analysed with baseline systolic BP as a covariate in an ANCOVA model. Then, the RH group was subdivided into those with SBP above or below 130mmHg at baseline and BP response to semaglutide assessed. Analyses were performed using R Software version 4.0.3. Results In the pooled analysis of 3136 trial participants, 111 met the criteria for RH. Compared to placebo, participants on semaglutide had a SBP reduction of -4.93mmHg, adjusted for SBP baseline to -3.16mmHg (95%CI -8.69 to 2.37). For those with RH and a baseline SBP > 130mmHg on semaglutide, the SBP change was -10.94mmHg. This change was 4.54mmHg for those with a SBP < 130mmHg. The diastolic BP changes were -3.62 and 2.79mmHg respectively (Figure 1). At trial completion, 36% of those on semaglutide did not meet the criteria for RH. Conclusions The effect of semaglutide on BP for patients with RH is modest. A greater BP reduction is evident for those with a higher baseline SBP. Targeting excess body weight with semaglutide is a viable treatment option for patients with RH and uncontrolled BP.