Adult patients with type 2 diabetes and a history of cardiovascular or kidney disease may have fewer major adverse cardiovascular events when treated with oral semaglutide compared with those treated with placebo, according to the SOUL trial.
In the trial, researchers enrolled 9,650 patients aged 50 or older from 33 countries. All of them had type 2 diabetes and either atherosclerotic cardiovascular disease, chronic kidney disease, or both. The participants were randomly assigned to receive 14 mg of oral semaglutide or placebo once daily in addition to standard care.
Over a median follow-up of 49.5 months, 12.0% of participants in the semaglutide group experienced a MACE vs 13.8% in the placebo group. Events included cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke. The incidence rates were 3.1 vs 3.7 per 100 person-years, respectively (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77–0.96, P = .006).
The absolute risk reduction at 3 years was 2 percentage points. The number needed to treat (NNT) to prevent one event was 50 (95% CI = 31–125).
Among the primary endpoint components, nonfatal myocardial infarction showed the greatest difference—4.0% in the semaglutide group vs 5.2% in placebo (HR = 0.74, 95% CI = 0.61–0.89). Rates of cardiovascular mortality and nonfatal stroke were similar between the groups.
The first confirmatory secondary outcome—major kidney disease events—occurred in 8.4% of the semaglutide group and 9.0% of the placebo group (HR = 0.91, 95% CI = 0.80–1.05, P = .19), a difference that was not statistically significant. As a result, further secondary outcomes were not formally tested.
At week 104, the semaglutide group had a mean reduction in HbA1c of –0.71 percentage points vs –0.15 with placebo. The mean weight loss was –4.22 kg vs –1.27 kg.
Serious adverse events occurred in 47.9% of the patients in the semaglutide group and 50.3% of those in the placebo group. Gastrointestinal side effects were more frequent with semaglutide (5.0% vs 4.4%) and contributed to higher treatment discontinuation (15.5% vs 11.6%).
The benefits of semaglutide appeared consistent across prespecified subgroups, including age, baseline HbA1c, and kidney function.
“Oral semaglutide was superior to placebo in reducing the risk of major adverse cardiovascular events,” concluded lead study author Darren K. McGuire, MD, MHSc, of the University of Texas Southwestern Medical Center, and colleagues.
Full disclosures are available in the published study.