medwireNews: The STEP 6 findings reveal significant weight loss, along with a reduction in abdominal visceral fat, in east Asian people with obesity taking a high dose of semaglutide.
As reported in The Lancet Diabetes & Endocrinology, the average bodyweight reduction during 68 weeks of treatment was 13.2% in the 199 participants randomly assigned to receive semaglutide 2.4 mg/week, compared with 2.1% in the 101 people taking placebo.
The investigators also tested a lower dose of 1.7 mg/week for regulatory purposes; this produced an average bodyweight reduction of 9.6% in 101 participants, which was also significantly greater than the change in the placebo group.
The team noted bodyweight reductions of at least 5%, 10%, or 15% occurring in 83%, 61%, and 41% of the semaglutide 2.4 mg group, respectively, compared with just 21%, 5%, and 3% of the placebo group.
The study participants came from Japan or South Korea and had a BMI of at least 27 kg/m2 and two or more weight-related comorbidities, or of at least 35 kg/m2 with at least one comorbidity. One of the comorbidities had to be hypertension or dyslipidemia; in addition, a subset of Japanese participants, comprising 25% of the total trial population, had type 2 diabetes.
Semaglutide treatment produced significant improvements in blood pressure, lipid profiles, and inflammatory markers, as well as around a 2% reduction in glycated hemoglobin in people with type 2 diabetes.
The average reductions in waist circumference were 11.1, 7.7, and 1.8 cm in the semaglutide 2.4, semaglutide 1.7 mg, and placebo groups, respectively. In line with this, among 180 participants who had baseline and follow-up computed tomography scans, there were average 40.0% and 22.2% reductions in abdominal visceral fat area in the semaglutide 2.4 and 1.7 mg groups, respectively, compared with 6.9% in the placebo group.
Semaglutide treatment also produced significantly greater reductions than placebo in the number of people with an abdominal visceral fat area of 100 cm2 or greater, a threshold that Takashi Kadowaki (Toranomon Hospital, Tokyo, Japan) and co-researchers say “is a strong indicator for risk of obesity-related diseases in people from east Asia with obesity, potentially due to genetically-determined molecular mechanisms.”
As anticipated, the most common adverse events were gastrointestinal, and these were “mostly transient and mild or moderate in severity,” say the researchers, who also note that these were not dose-dependent, with the highest rate reported in the semaglutide 1.7 mg group.
In a linked commentary, Tricia Tan (Imperial College London, UK) and Bernard Khoo (University College London, UK) note that the reduction in abdominal visceral fat “suggests that semaglutide has a clinically significant effect on the pathophysiology of metabolic syndrome.”
They also observe that the publication of STEP 6 offsets the other trials from the series, in which “participants from Asia were a decided minority, which is not reflective of the global situation regarding obesity.”
The commentators believe these results in Japanese and Korean people are likely generalizable to other Asian populations but note that data from Chinese people will be forthcoming in the ongoing STEP 7.
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Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00008-0
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