Semaglutide confers ASCVD risk factor benefits in high-risk patients

Treatment with semaglutide yields early and sustained improvements in multiple atherosclerotic cardiovascular disease (ASCVD) factors in high-risk patients with type 2 diabetes (T2D) and ASCVD and/or chronic kidney disease (CKD), according to a post hoc analysis of the SOUL trial.

SOUL included 9,650 randomized participants (mean age 66.1 years, 28.9 percent female), of which 4,825 received once-daily oral semaglutide (maximum dose 14 mg) and 4,825 received placebo. All participants received standard of care.

Outcomes included changes in glycated haemoglobin (HbA1c), body weight, blood pressure (BP), and plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipids.

A total of 9,495 participants (98.4 percent) completed the trial, with a mean follow-up of 47.5 months.

Compared with the placebo group, the semaglutide group showed marked improvements in HbA1c (−0.87 percentage points), body weight (−2.54 percent), systolic BP (SBP, −3.84 mm Hg), pulse pressure (−3.81 mm Hg), hsCRP (−18.08 percent), total cholesterol (TC, −7 percent), non–high-density lipoprotein cholesterol (non–HDL-C, −8.02 percent), HDL-C (−4.49 percent), and triglycerides (−8.15 percent) as early as week 13. These improvements were sustained throughout the trial duration.

Weight loss occurred gradually in both treatment groups.

At week 156, semaglutide was associated with more favourable effects on HbA1c (estimated treatment difference [ETD], −0.47 percentage points, 95 percent confidence interval [CI], −0.52 to −0.42), body weight (ETD, −3.26 percentage points, 95 percent CI, −3.55 to −2.98), SBP (−1.83 mm Hg, 95 percent CI, −2.47 to −1.18), pulse pressure (ETD, −2.17 mm Hg, 95 percent CI, −2.72 to −1.61), hsCRP (estimated treatment ratio [ETR], 0.77, 95 percent CI, 0.74–0.81), total cholesterol (ETR, 0.99, 95 percent CI, 0.98–1.00), non–high-density lipoprotein (HDL) cholesterol (ETR, 0.98, 95 percent CI, 0.97–0.99), HDL cholesterol (ETR, 1.01, 95 percent CI, 1.01–1.02), and triglycerides (ETR, 0.94, 95 percent CI, 0.93–0.96) compared with placebo.

No significant treatment differences were seen for low-density lipoprotein cholesterol or diastolic BP.