STEP 1

In patients with obesity, but without diabetes, does the use of the GLP-1 agonist semaglutide result in significant weight loss?

Study design: Multi-center, double-blind, randomized, placebo-controlled trial

Population

Number of patients studied: 1,961
Inclusion criteria: Age ≥18 years old; BMI >30, or ≥27 with ≥1 weight-related comorbidity; ≥1 self-reported unsuccessful dietary attempts to lose weight
Exclusion criteria: Diabetes; HbA1c ≥6.5%; history of pancreatitis; prior obesity treatments; recent significant weight change; abnormal TSH; severe psychiatric disorders; renal impairment; recent cardiovascular events; general safety exclusions

Interventions

Experimental group: Semaglutide 2.4 mg once weekly with lifestyle interventions (n=1,306)
Control group: Placebo with lifestyle interventions (n=655)

Primary outcome

Mean weight change from baseline to week 68: -14.9% (semaglutide) vs. -2.4% (placebo); Participants who achieved ≥5% weight reduction: 86.4% (semaglutide) vs. 31.5% (placebo)

Conclusion: Semaglutide resulted in significant weight loss compared to placebo in overweight and obese individuals without diabetes, with some gastrointestinal side effects and a signal towards more hepatobiliary complications

Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., ... & Walton, C. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989-1002.