In a recent study published in Nature Medicine, an international team of researchers investigated the effects of semaglutide on body weight and anthropometric measurements, safety and tolerability in obese but non-diabetic adults. We assessed across a range of baseline BMIs. ) Categories.
Study: Long-term weight loss effects of semaglutide in non-diabetic obesity in the SELECT trial. Image credit: Douglas Cliff / Shutterstock
background
Global obesity prevalence (BMI ≥30 kg m−2) has nearly tripled since 1975. Although BMI correlates with body fat at a population level, it may not accurately reflect an individual's fat mass or distribution. Excess body fat, especially visceral and ectopic fat, causes cardiovascular disease (CVD) and contributes to chronic diseases such as diabetes and cancer. Losing weight can reduce these effects, and moderate weight loss improves CV risk factors and quality of life. Achieving significant weight loss through lifestyle changes alone is difficult, but drugs like semaglutide have shown promise. Further research is needed to understand the long-term effects, optimal dosing, and potential side effects of semaglutide in diverse populations with different health conditions.
About research
This study follows ethical standards and analyzes the Effects of Semaglutide on Heart Disease and Stroke in Overweight or Obese Patients (SELECT) trial, a randomized, double-blind, placebo-controlled study. SELECT compared semaglutide 2.4 mg subcutaneously once weekly versus placebo to reduce major adverse cardiac events in overweight or obese individuals with established cardiovascular disease and no diabetes. evaluated. The study, which received regulatory and ethical approval, enrolled patients aged 45 years and older with a BMI of 27 kg/m or higher and established CVD. All participants provided informed consent.
The trial, designed by Novo Nordisk and an academic steering committee, randomly assigned patients to semaglutide or placebo. The starting dose was 0.24 mg weekly and increased every 4 weeks to his target of 2.4 mg. Dose adjustments were allowed based on tolerability. Although the researchers followed guidelines for treatment and lifestyle counseling to manage CVD, the counseling did not focus on weight loss.
Gender and ethnicity were self-reported, and physical measurements were taken according to a specific protocol. Endpoints included changes in body weight, waist circumference (WC), waist-to-height ratio (WHtR), and percent achieving significant weight loss.
97.1% of the semaglutide group and 96.8% of the placebo group completed the study, with 30.6% and 27.0%, respectively, discontinuing treatment. Statistical analyzes based on intention-to-treat principles used covariance models and multiple imputation of missing data, with analyzes performed using SAS software.
research result
The study enrolled 17,604 patients (72.3% male) from 41 countries between October 2018 and March 2021, with an average age of 61.6 years and a BMI of 33.3 kg/m2. Baseline characteristics of the population have been previously reported. In particular, the proportion of Asians was higher in the lower BMI categories, and the proportion of women increased as the BMI category increased. Lower BMI categories were associated with a higher proportion of normoglycemic patients and lower glycated hemoglobin levels. The proportion of patients with high cholesterol and a history of smoking was similar across BMI categories, whereas the proportion of patients with high-sensitivity C-reactive protein levels increased with higher BMI categories.
The 4-year average weight loss trajectory with semaglutide and placebo showed that weight loss continued through week 65 and was maintained through week 208. At week 208, the mean weight loss in the semaglutide group was 10.2%, while the mean weight loss in the semaglutide group was 1.5%. Placebo group. Initial on-treatment analysis showed that at week 208, mean weight loss was 11.7% in the semaglutide group and 1.5% in the placebo group. At week 104, weight loss was greater than 5%, greater than 10%, greater than 15%, and greater. 20%, 25% or higher were achieved in 67.8%, 44.2%, 22.9%, 11.0%, and 4.9% of the semaglutide-treated group, while 21.3%, 6.9%, 1.7%, and 1.7% of the semaglutide-treated group achieved They were 0.6% and 0.1%. For those receiving a placebo.
Changes in WC reflected changes in body weight, with an average decrease of 7.7 cm in the semaglutide group compared with 1.3 cm in the placebo group at week 208. Within the SELECT population with baseline BMI <35 kg/m-2, 15.0% of the semaglutide group and 14.3% of the placebo group were below gender- and race-specific WC cutoffs. By week 104, 41.2% of patients in the semaglutide group were below these cutoff points, compared with 18.0% in the placebo group. Mean WHtR at baseline was 0.66 and decreased by 6.9% in the semaglutide group compared to 1.0% in the placebo group by week 208.
At week 104, 52.4% of patients treated with semaglutide improved in BMI category, compared with 15.7% of patients receiving placebo. The proportion of obese patients (BMI ≥ 30 kg/m-2) decreased from 71.0% to 43.3% in the semaglutide group, compared with 71.9% to 67.9% in the placebo group. Safety and tolerability were also evaluated, and semaglutide was associated with lower rates of serious adverse events (SAEs) across all BMI categories. The incidence of SAEs per 100 years of observation was lower in the semaglutide group compared with the placebo group, but there were no significant differences in hepatobiliary or gastrointestinal SAEs between the two groups.
