Materials and methods
In the SELECT study, patients with obesity and cardiovascular diseases treated with semaglutide had a 20% relative reduction in the risk of developing MACE. The researchers conducted an interim analysis to determine which treatment-related changes explained this benefit.
The study involved 17,604 adults aged 45 years and older with a BMI of 27 and above, who had cardiovascular diseases and did not have diabetes. The average age of the patients was 62 years, 72% of them were men.
Patients were randomly assigned to subcutaneous administration of semaglutide once a week (at a dose of 2.4 mg for 16 weeks) or an appropriate placebo.
The researchers tracked repeated measurements of 12 potential mediators, including body weight, waist circumference, blood pressure, and levels of highly sensitive C-reactive protein (hsCRP), A1c, and lipids, at different time points over a period of at least 24 months.
The primary endpoint was MACE, which was defined as nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular disease. The average follow-up period was 39.8 months.
Results
The use of semaglutide was associated with a significant improvement in all 12 assessed risk factors (P < 0.05).
Waist circumference was estimated to account for 64.0% of the benefit from semaglutide (95% CI 27.5-179.6), the hsCRP level - 42.1% (95% CI 17.9-110.5), the A1c level - 29.0% (95% CI from -20.7 to 120.5), and body weight - 19.5% (95% CI from -33.0 to 110.7). All estimates had wide CI values.
The combination of eight key risk factors explains 31.4% of the benefit of semaglutide (95% CI -30.1 to 143.6). Other factors besides body weight and waist circumference accounted for 46.0% of the benefit (95% CI -6.0 to 161.0).
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