ABSTRACT
In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .
ABSTRACT
We assessed the effect of semaglutide 2.4 and 1.7 mg versus placebo on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL) in the STEP 6 trial. Adults from East Asia (body mass index [BMI] ≥27.0 kg/m2 with ≥2 weight-related comorbidities, or ≥35.0 kg/m2 with ≥1 weight-related comorbidity) were randomized 4:1:2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, or semaglutide 1.7 mg or placebo, plus lifestyle intervention for 68 weeks. WRQOL and HRQOL were assessed from baseline to Week 68 using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) and the 36-Item-Short-Form-Survey-version-2.0 acute (SF-36v2), with changes in scores by categories of baseline BMI (≥30 and ≥35 kg/m2 ) also assessed. In total, 401 participants (mean body weight 87.5 kg, aged 51 years, BMI 31.9 kg/m2 , waist circumference 103.2 cm) were included. From baseline to Week 68, the IWQOL-Lite-CT Psychosocial and Total scores were significantly improved with semaglutide 2.4 and 1.7 mg versus placebo. For Physical score, effects were only in favour of semaglutide 2.4 mg versus placebo. In the SF-36v2, Physical Functioning was significantly improved with semaglutide 2.4 mg versus placebo, but no beneficial effects favouring either semaglutide treatment arms versus placebo were seen in the other SF-36v2 domains. Benefits favouring semaglutide 2.4 mg versus placebo were also observed in subgroups with higher BMIs for IWQOL-Lite-CT and SF-36v2 Physical Functioning scores. Treatment with semaglutide 2.4 mg improved aspects of WRQOL and HRQOL in people from East Asia with overweight/obesity.