Impact of oral semaglutide on cardiovascular risk factors in patients with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease: a SOUL post hoc analysis

Introduction In the SOUL trial, once-daily oral semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the risk of major adverse cardiovascular (CV) events by 14% compared with placebo in people with type 2 diabetes (T2D) and atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD). Purpose To investigate the treatment effect of oral semaglutide versus placebo on CV risk factors in the SOUL trial. Methods In SOUL, 9650 participants with T2D and ASCVD and/or CKD, all receiving standard of care, were randomised to oral semaglutide or placebo and followed for a mean of 47.5 months. These post hoc analyses of intention-to-treat data from SOUL evaluated the treatment effect of oral semaglutide compared with placebo on glycated haemoglobin (HbA1c), body mass index (BMI) and blood pressure (BP, including systolic BP [SBP], diastolic BP [DBP] and mean arterial BP [MAP]), using estimated treatment differences (ETDs), and on plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipids, using estimated treatment ratios (ETRs); measurements were at baseline and weeks 13, 52, 104, 156 and 208 (statistical comparison was done for data at week 156, due to the low number patients at week 208), except for hsCRP (weeks 13 and 104 only). Results These analyses included all randomised participants (4825 in each group); 98.4% completed the trial. Changes in HbA1c, BMI, SBP and hsCRP ratio to baseline are shown in Figure 1 and changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides ratio to baseline are depicted in Figure 2. At week 156, ETDs were in favour of oral semaglutide for HbA1c, BMI, SBP and ETRs for hsCRP, TC, HDL-C and triglycerides, but no significant treatment differences were observed for LDL-C, DBP or MAP. Conclusion Oral semaglutide shows sustained improvements in multiple CV risk factors (SBP, hsCRP, TC, HDL-C and triglycerides), in addition to HbA1c and BMI, in a relatively large sample of high-risk patients with T2D and ASCVD and/or CKD.