Cardiovascular outcomes by baseline blood pressure control status in persons with type 2 diabetes at high cardiovascular risk treated with oral semaglutide

Introduction Oral semaglutide was associated with significant reduction in major adverse cardiovascular events (MACE) vs placebo in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD) in the SOUL trial (NCT03914326). Purpose Given the frequent coexistence and importance of raised blood pressure (BP) in T2D as determinant of MACE, these post hoc exploratory analyses aimed to assess the associations between baseline BP control status and the effect of oral semaglutide on cardiovascular (CV) outcomes in SOUL. Methods Overall, 9650 participants with T2D (defined as HbA1c 6.5–10%) and ASCVD and/or CKD, aged ≥50 years, were randomised to oral semaglutide or placebo. For these analyses, participants were grouped by baseline BP control status. BP was measured in the sitting position using standard procedures. Controlled BP was defined as <130/80 mmHg and uncontrolled BP as ≥130/80 mmHg. Cox proportional hazards models were used to estimate the effect of oral semaglutide on CV outcomes, including time to first 3-point (3pt) MACE (occurrence of non-fatal myocardial infarction [MI], non-fatal stroke or CV death), time to each 3pt MACE component and time to all-cause death, by baseline BP control. Changes in systolic BP (SBP) and diastolic BP (DBP) from baseline to week 104 by baseline BP control status were estimated using an analysis of covariance model. Results Of 9646 participants with BP data, 2767 had controlled BP and 6879 had uncontrolled BP at baseline (Table). Participants with controlled BP had more frequent history of MI or stroke and coronary revascularisation before SOUL, but similar levels of CV risk factors and BP medication use. There was no significant difference in BP control status between treatment groups at baseline; at week 104, the difference was significant (participants with controlled BP, oral semaglutide: 35.2% vs placebo: 31.3%, p=0.0001). Oral semaglutide use was associated with modest reductions in SBP, but not in DBP, vs placebo, after 104 weeks in both controlled and uncontrolled groups. For SBP, the estimated treatment difference for oral semaglutide vs placebo (95% CI) was −1.81 (−2.97;−0.64; p=0.002) in the controlled BP group and −1.67 (−2.41;−0.94; p<0.0001) in the uncontrolled BP group. For all CV outcomes, there was no significant difference in hazard ratio (HR) between those with controlled or uncontrolled BP, with significant reductions observed in risk of 3pt MACE (controlled BP, HR: 0.80, 95% CI: 0.65;0.99; uncontrolled BP, HR: 0.87, 95% CI: 0.76;0.99; p=0.55) and non-fatal MI (controlled BP, HR: 0.67, 95% CI: 0.47;0.94; uncontrolled BP, HR: 0.77, 95% CI: 0.62;0.97; p=0.49) for participants treated with oral semaglutide vs placebo (Figure). Conclusion Oral semaglutide led to modest reductions in SBP and consistent reductions in CV outcomes in people with T2D with ASCVD and/or CKD, irrespective of baseline BP control status.