Physicians' Academy for Cardiovascular Education

Direct comparison of the efficacy of two GLP-1RA on weight loss in overweight and obese adults

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

Literature - Rubino DM, Greenway FL, Khalid U et al. - JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619.

Introduction and methods

Aim of the study

This study directly compared the efficacy two GLP-1RA, semaglutide and liraglutide, on weight loss, added to counseling for diet and physical activity, in adults with overweight or obesity without diabetes.


Eligible participants were ≥18 years old and had a BMI ≥30 or ≥27 with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea or CVD). People with diabetes, HbA1c ≥6.5% and self-reported body weight changes >5 kg within 90 days prior to screening were excluded.

A total of 338 participants were randomized in a 3:1:3:1 ratio to receive once-weekly subcutaneous semaglutide (2.4 mg, n=126), or matching placebo, or once-daily subcutaneous liraglutide (3.0 mg, n=127), or matching placebo for 68 weeks. Placebo groups were pooled (n=85). Due to dosing differences, assignment to semaglutide or liraglutide was not blinded. In contrast, assignment to active treatment or placebo was double-blinded.

Semaglutide was initiated at 0.25 mg and escalated to 2.4 mg over 16 weeks. If the target dose of 2.4 mg could not be tolerated, a maintenance dose of 1.7 mg was allowed. Liraglutide was initiated at 0.6 mg and escalated to 3.0 mg over 4 weeks. If a dose of 3.0 mg was not tolerated, liraglutide was discontinued. The treatment could be restarted.

All participants received counseling for diet and physical activity recommendations.



The primary outcome was percentage change in body weight from baseline to week 68 in the semaglutide versus liraglutide group. Confirmatory secondary endpoints included the proportion of participants in the semaglutide versus liraglutide group who achieved a weight loss of ≥10%, ≥15% and ≥20% by week 68.

Supportive secondary endpoints included comparisons versus the pooled placebo group and changes from baseline to week 68 in absolute body weight, waist circumference, blood pressure, fasting lipid concentrations, CRP, HbA1c, fasting plasma glucose, fasting serum insulin, glycemic status, and permanent discontinuations of study drug for semaglutide versus liraglutide.

Main results

Percentage change in body weight

Weight loss of ≥10%, ≥15% or ≥20%

Other secondary outcomes



Treatment with once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, led to significantly greater weight loss at 68 weeks in adults with obesity or overweight without diabetes.

Find this article online at JAMA.

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