Semaglutide Superior to Liraglutide for Weight Loss in Head-to-Head Study

ObesityWeek 2021. Weight loss with semaglutide was more than 2 times greater than with liraglutide in the 68-week placebo-controlled trial of the 2 GLP-1 RAs.

Once-weekly semaglutide 2.4 mg was found superior to daily liraglutide for weight reduction in adults with overweight/obesity, according to findings of the STEP 8 clinical trial announced at ObesityWeek 2021.

Patients treated with semaglutide lost more than twice the weight of liraglutide-treated patients during the 68-week trial and also experienced improvements in cardiometabolic risk factors vs participants in the liraglutide group, according to the study abstract.

The randomized, active-controlled STEP 8 trial, led by Domenica M. Rubino, MD, director, Washington Center for Weight Management and Research, enrolled 338 US adults with body mass index (BMI)≥27 kg/m2 and ≥1 weight-related comorbidity, or BMI ≥30 kg/m2, without diabetes.

Mean age of participants was 49 years and 78.4% were women. Mean body weight at study baseline was 104.5 kg and mean BMI 37.5 kg/m2.

Rubino and colleagues randomized participants (3:1:3:1) to semaglutide 2.4 mg once weekly (N=126) or matching placebo (PBO), or liraglutide 3.0 mg daily (N=127) or matching placebo. All participants received the same lifestyle intervention. The authors note that while treatment arm assignment of participants was not blinded, within each arm receipt of active drug vs placebo was double-blinded.

The study’s primary endpoint for analysis at week 68 was percentage change in body weight in the semaglutide- vs liraglutide-treated groups. Confirmatory secondary endpoints were the proportion of participants in each treatment group that achieved weight loss of ≥10%, ≥15%, and ≥20%. The secondary endpoint, assessed by the treatment policy estimand, was change in cardiometabolic risk factors.


From baseline to week 68, the researchers report, the mean change in body weight for semaglutide-treated patients was –15.8% vs –6.4% for those treated with liraglutide (estimand treatment difference: –9.4%-points [95% confidence interval: –12.0, –6.8]; p<.001).

Analysis of the confirmatory secondary endpoint found that greater proportions of participants in the semaglutide group vs the liraglutide group achieved weight loss of ≥10% (70.9% vs 25.6%); ≥15% (55.6% vs 12.0%); and ≥20% (38.5 vs 6.0%); (p<.001 for all odds ratios).

Cardiometabolic risk factors also improved with semaglutide vs liraglutide treatment including waist circumference, HgbA1c, and c-reactive protein level (unadjusted p<.001 for all). No data were reported for placebo.

Evaluation of adverse events (AEs) found that gastrointestinal AEs, common to the glucagon-like peptide-1 receptor agonist class, were reported by 84.1% of semaglutide-treated and 82.7% of liraglutide-treated participants, although the authors write that most events were mild or moderate and transient and that prevalence declined over the course of the study. While 12.6% of participants stopped treatment related to liraglutide AEs, 3.2% discontinued because of semaglutide-related AEs.

Rubino et al write in the conclusion to the study abstract that semaglutide was superior to liraglutide at “meaningfully reducing” body weight and improving measures of cardiometabolic risk and that no new safety signals were identified.

Reference: Rubino DM, Greeway FL, Khalid U, et al. Semaglutide 2.4 mg vs liraglutide 3.0 mg for weight management in overweight or obesity (STEP 8). Paper presented at: ObesityWeek 2021; November 1-5, 2021; held online.