Daily oral semaglutide confers weight loss vs. placebo; similar vs. weekly injectables
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Key takeaways:
- Daily oral semaglutide was tied to more weight loss vs. placebo plus lifestyle interventions in people with overweight or obesity.
- Efficacy and safety was similar vs. larger oral doses and weekly injectables.
SAN ANTONIO — Once-daily oral semaglutide conferred more weight loss vs. placebo plus lifestyle intervention and was similar vs. larger oral GLP-1 receptor agonist doses and weekly injectables for efficacy and safety, a speaker reported.
At ObesityWeek, W. Timothy Garvey, MD, FACE, MABOM, endocrinologist and professor at the University of Alabama at Birmingham and principal investigator of the UAB Diabetes Research Center, presented the results of the double-blind, randomized-controlled OASIS 4 trial of once-daily oral semaglutide 25 mg (Novo Nordisk) for people with overweight or obesity.
“The STEP program has shown that subcutaneous semaglutide is efficacious in treating people with overweight and obesity. But the availability of an oral formulation of semaglutide for obesity could provide a convenient alternative to the injectable,” Garvey said during the presentation. “OASIS 1, a phase 3 trial, which examined the efficacy and safety of a higher, 50-mg dose per day of oral semaglutide, showed efficacy, with 15.1% weight loss versus 2.4% for placebo in patients with overweight and obesity, and also improved cardiometabolic risk factors. OASIS 4 is designed to evaluate the efficacy and safety of a lower dose once per day, 25 mg vs. placebo.”
For the OASIS 4 trial, the researchers randomly assigned 307 adults with of BMI at least 30 kg/m2 or at least 27 kg/m2 with at least one weight-related comorbidity (mean age, 48 years; 79% women; 92% white; mean BMI at baseline, 37.6 kg/m2) to once-daily oral semaglutide or placebo for 64 weeks on top of lifestyle intervention, which consisted of at least 150 minutes of physical activity each week and a –500 kcal per day deficit diet.
Semaglutide dose was escalated to 25 mg over the course of 12 weeks and maintained for 52 weeks.
The co-primary endpoints were weight change and achievement of 25% weight loss. Secondary endpoints were achievement of at least 10%, 15% or 20% weight loss and change in Impact of Weight on Quality of Life-Lite Clinical Trials Physical Function score.
In total, 81.5% of participants assigned to oral semaglutide completed the trial, which was more than the 74.5% of placebo-assigned participants who completed OASIS 4.
The average percentage weight loss in the oral semaglutide groups was 13.6% compared with 2.2% in the placebo group (estimated treatment difference, –11.4 percentage points; 95% CI, –13.9 to –9; P < .0001) and was 16.6% and 2.7%, respectively when the researchers used the on-treatment data (estimated treatment difference, –13.9 percentage points; 95% CI, –16.5 to –11.2; P < .0001), according to the presentation.
People assigned to daily oral semaglutide were more likely have significant weight loss compared with those assigned to placebo:
- at least 5% weight loss (OR = 7.3; 95% CI, 4.2-12.8);
- at least 10% weight loss (OR = 9.1; 95% CI, 4.7-17.3);
- at least 15% weight loss (OR = 15.7; 95% CI, 6.2-40.2); and
- at least 20% weight loss (OR = 12.2; 95% CI, 3.7-40.3; P for all < .0001).
The researchers also observed a significant improvement in Impact of Weight on Quality of Life-Lite Clinical Trials Physical Function score among those assigned to daily oral semaglutide, with an estimated 7.7 treatment difference (P = .0006) compared with placebo.
Improvements were also reported in parameters including waist circumference, C-reactive protein, fasting glucose, HbA1c and across participants’ lipid profile for those assigned to semaglutide.
At baseline, nearly half of trial participants had prediabetes, while the remainder had normoglycemia. At 64 weeks, approximately 71% of individuals with prediabetes reverted to normoglycemia compared with 33% assigned to placebo.
Most adverse events were gastrointestinal-related (74%), with the most common symptoms being nausea (46.6%), vomiting (30.9%) and constipation (20.1%). Gastrointestinal-related adverse events also occurred in 42.2% of the placebo arm, according to the study.
“The OASIS 4 trial showed that once-daily oral semaglutide 25 mg worked pretty well. There was significant weight loss, improvement in physical function and improvements in cardiometabolic risk factors. The weight loss on 25 mg was comparable to those reported at 50 mg in OASIS 1 and 2.4 mg subcutaneously weekly in STEP 1,” Garvey said during the presentation. “The safety profile was consistent with the known safety profile for GLP-1 receptor agonists. Oral 25 mg may represent an efficacious option for treatment of overweight and obesity, particularly in patients who prefer oral administration.”
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Garvey WT. Oral-108. Presented at: ObesityWeek; Nov. 3-6, 2024; San Antonio.
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