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Abstract Background Randomised clinical trials of patients with obesity treated with semaglutide (STEP trials) reported clinically significant reductions in blood pressure (BP). The mean baseline BP of trial participants was in the normal range. The effect of semaglutide on patients with hypertension has yet to be elucidated. Purpose To determine the blood pressure effect of semaglutide in patients with uncontrolled BP at randomization (baseline BP). Methods Individual participant data from three randomised placebo-controlled trials examining the effect of semaglutide 2.4mg on body weight (STEP 1, 3 and 4) over 68 weeks were included (the Cohort). Participants with systolic BP (SBP) 140mmHg at baseline were identified (HTN140 group). The effect of semaglutide on SBP estimated by ANCOVA with baseline SBP as a covariate. Adjustments of antihypertensive treatment (escalated if treatment started or dose increased; de-escalated if treatment stopped or dose decreased) were assessed using logistic regression analysis adjusted for baseline SBP. Results 3136 participants were included in the pooled analysis. 397 (13%) had a baseline SBP 140mmHg (semaglutide arm, n=257; placebo arm, n=140). The baseline BP and body weight of the HTN140 group were comparable between treatment arms Table 1. The effect of semaglutide on SBP was estimated as -4.09mmHg (95% CI -7.12 to -1.06, p0.05). This effect was comparable to that for the Cohort (-4.95mmHg; 95% CI -5.86 to -4.05, p0.05). The observed SBP reduction was 17.41mmHg for those in the semaglutide arm and 12.57mmHg in the placebo arm (Figure 1). This large in-trial effect was partly due to the escalation of anti-hypertensive treatment in 11.3% and 14.3% of participants randomized to semaglutide and placebo respectively (OR 0.76; 95% CI 0.39 to 1.49, p=0.42). Conclusions The effect of semaglutide on SBP was not greater in patients with uncontrolled SBP at randomization compared to the Cohort of all patients in STEP 1, 3, 4. The adjustment of anti-hypertensive medications contributed to a large observed reduction in SBP for both trial arms. This demonstrates the Hawthorne effect during these trials. Effect on SBP
Kennedy et al. (Sat,) studied this question.