Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

Literature - Knop FK, Aroda VR, do Vale RD, et al. - Lancet. 2023 Jun 23;S0140-6736(23)01185-6 [Online ahead of print]. doi: 10.1016/S0140-6736(23)01185-6

Introduction and methods

Background

While subcutaneous semaglutide 2.4 mg once a week has been approved for the treatment of overweight and obesity, availability of an oral formulation of this GLP-1RA could provide an additional therapeutic option for this population.

Aim of the study

The study aim was to evaluate the efficacy and safety of oral semaglutide 50 mg once daily in patients with overweight or obesity but no T2DM.

Methods

The OASIS (Oral Semaglutide Treatment Effect in People with Obesity) 1 trial was an international, multicenter, double-blind, placebo-controlled, phase 3, superiority RCT in which 667 adults with either a BMI of ≥30 kg/m² or a BMI of ≥27 kg/m² with ≥1 body weight–related complications or comorbidities (i.e., hypertension, dyslipidemia, obstructive sleep apnea, or CVD), but no T2DM, were enrolled. Participants were randomized in a 1:1 ratio to oral semaglutide escalated to 50 mg or visually identical placebo once daily for 68 week, as an adjunct to lifestyle intervention. Thereafter, patients underwent an off-treatment follow-up for 7 weeks.

Outcomes

The 2 coprimary endpoints were: (1) percentage change in body weight from baseline to 68 weeks, and (2) weight reduction of ≥5% at 68 weeks (intention-to-treat analysis). Confirmatory secondary endpoints were weight reduction of ≥10%, ≥15%, or ≥20% at 68 weeks, and change from baseline to 68 weeks in patient-reported physical function outcomes as assessed with 2 questionnaires.

Safety assessments included the number of treatment-emergent adverse events and serious adverse events assessed up to 75 weeks.

Main results

Efficacy

• The estimated mean body weight change from baseline to 68 weeks was –15.1% (SE: 0.5) in patients receiving semaglutide (n=334) and –2.4% (SE: 0.5) in placebo-treated patients (n=333) (estimated treatment difference: –12.7 percentage points; 95%CI: –14.2 to –11.3; P<0.0001).
• At 68 weeks, more patients in the semaglutide group had reached a weight reduction of ≥5% than in the placebo group (269/317 (85%) vs. 76/295 (26%); OR: 12.6; 95%CI: 8.5–18.7; P<0.0001).
• Patients in the semaglutide group were also more likely to reach a ≥10% weight reduction (69% vs. 12%; OR: 14.7; 95%CI: 9.6–22.6; P<0.0001), a ≥15% weight reduction (54% vs. 6%; OR: 17.9; 95%CI: 10.4–30.7; P<0.0001), and a ≥20% weight reduction (34% vs. 3%; OR: 18.5; 95%CI: 8.8–38.9; P<0.0001).
• In addition, patient-reported physical function outcomes showed significant improvements with semaglutide versus placebo (both P<0.0001).

Safety

• More adverse events were observed in the semaglutide group (92%) compared with the placebo group (86%). Adverse events leading to discontinuation of the study drug (mostly gastrointestinal) occurred in 6% and 4%, respectively.
• The most frequently reported adverse events were gastrointestinal (nausea, constipation, diarrhea, and vomiting). These events were reported by 80% of the patients receiving semaglutide and 46% of those taking placebo and were typically transient and mild to moderate in severity.
• Serious adverse events were reported by similar proportions in the semaglutide and placebo groups (10% vs. 9%).
• During the trial, the pulse rate increased by 4.1 bpm (SE: 05) in semaglutide-treated patients and decreased by 0.4 bpm (SE: 05) in placebo-treated patients.

Conclusion

Find this article online at The Lancet.