STEP 8: Greater weight loss for once-weekly semaglutide vs daily liraglutide
Once-weekly subcutaneous semaglutide (2.4mg) is more effective on weight loss in conjunction with counselling and physical activity vs once-daily subcutaneous liraglutide (3.0mg), according to the outcomes from the Semaglutide Treatment Effect in People With Obesity (STEP) 8 randomised clinical trial. The study, which included 338 participants, reported that the mean body weight change from baseline to 68 weeks was -15.8% with semaglutide vs. -6.4% with liraglutide. The findings were published in the paper, ‘Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes - The STEP 8 Randomized Clinical Trial’, featured in JAMA. The trial was funded by Novo Nordisk.
The STEP 8 study was conducted at 19 US sites from September 2019 to May 2021 in 338 adults with BMI>30 or >27 with one or more weight-related comorbidities, without diabetes. Participants were randomised (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n=126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity.
Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the four-week titration. Placebo groups were pooled (n=85). Semaglutide and liraglutide are modified, long-acting analogues of native glucagon-like peptide-1 (GLP-1).
A majority of participants were white (73.7%) and female (78.4%) with a mean body weight was 104.5 kg, mean BMI 37.5, mean waist circumference was 113.3cm and 36.1% had prediabetes. Most had 0 to 2 comorbidities at screening, with dyslipidaemia and hypertension being the most prevalent. Of the randomised participants, 80.2% (n=271) completed treatment (on-treatment at week 68) and 94.4% (n=319) completed the trial (attended week 75 end–of–follow-up visit).
At week 68, the estimated mean change in body weight was –15.8% with semaglutide and –6.4% with liraglutide (p<0.001). The proportions of participants achieving 10% or more, 15% or more and 20% or more weight loss were 70.9%, 55.6%, and 38.5% with semaglutide and 25.6%, 12.0%, and 6.0% with liraglutide, respectively. The odds of achieving weight loss of 10% or more, 15% or more and 20% or more were significantly greater with semaglutide vs with liraglutide (p<0.001 for all) Overall, 67 participants (19.8%) permanently discontinued treatment and discontinuations rates were greatest with liraglutide (27.6%), then placebo (17.6%) and semaglutide (13.5%).
At week 68, reductions in absolute body weight, waist circumference, total cholesterol level, very low-density lipoprotein cholesterol level, triglyceride level, HbA1c level, fasting plasma glucose level and C-reactive protein level were significantly greater with semaglutide vs with liraglutide. Changes in other end points were not significantly different. The reduction in diastolic blood pressure was significantly greater with semaglutide vs liraglutide at week 68, but changes at all other time points were comparable. Systolic blood pressure increased with placebo.
Adverse events (AEs) were reported by 95.2% of participants with semaglutide, 96.1% with liraglutide and 95.3% with placebo. Gastrointestinal disorders were the most frequent AEs with semaglutide and liraglutide, reported by 84.1% and 82.7% of participants, respectively, and more events occurred with semaglutide than with liraglutide.
“Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide, compared with once-daily subcutaneous liraglutide, added to counselling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks,” the authors concluded.
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