The US Food & Drug Administration (FDA) has approved the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for weight loss and to reduce the risk of major adverse cardiovascular events (MACE).
Novo Nordisk plans to launch its once-daily Wegovy 25 mg pill in the US this month, reports AJMC.
The approval is based on results from the OASIS clinical trials and the SELECT trial. OASIS 4 showed a mean weight loss of 13.6% at 64 weeks. The study evaluated the efficacy and safety of once-daily oral semaglutide with lifestyle counselling compared with placebo.
The OASIS 4 trial enrolled 307 adults without diabetes who were obese or overweight (body mass index [BMI] of ≥ 30 or ≥ 27 with at least one obesity-related complication) who received either oral semaglutide (n = 205) or placebo (n = 102). The coprimary end points were the percent change in body weight and a reduction of 5% or more in body weight at week 64.
Patients on oral semaglutide recorded a significantly greater mean change in body weight from baseline to week 64 compared with patients on placebo (–13.6% vs –2.2%; 95% CI, –13.9% to –9.0%; P < .001).
The study also estimated the hypothetical trial-product estimand, which estimates treatment effect assuming patients adhere to the treatment as assigned, resulting in a mean change in body weight of –16.6% for oral semaglutide and 2.7% for placebo (95% CI, –16.5% to –11.2%).
Not only was the reduction in relative body weight similar across subgroups based on BMI at baseline, but there was also no evidence the effect varied by sex, race, or ethnic group.
Most adverse events experienced by 93.1% of patients on oral semaglutide and 85.3% of patients on placebo were mostly mild or moderate and resulted in no permanent discontinuation of treatment.
The most frequent AEs were gastrointestinal disorders (74.0% oral semaglutide and 42.2% placebo).
Oral semaglutide was first approved in 2019 for type 2 diabetes, when it became the first oral GLP-1 approved by the FDA
Most recently, the agency had expanded the indication for semaglutide tablets 7 and 14 mg to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes who are at an elevated risk.
The indication also covered patients without a prior heart attack or stroke.
Competition on the horizon
The FDA decision gives oral semaglutide an edge in a competitive weight loss market, with Eli Lilly having submitted its own oral GLP-1, orforglipron, to the FDA for review.
Orforglipron is an investigational, non-peptide, once-daily oral GLP-1 receptor agonist that can be taken without restrictions on food or water intake.
Topline results from the phase 3 ATTAIN-MAINTAIN trial showed orforglipron met the primary end point of superior percent maintenance of body weight reduction compared with placebo.
In addition, patients who switched from semaglutide to orforglipron maintained their previously achieved weight loss.
The change in body weight from baseline to 24 weeks for patients who switched from semaglutide to orforglipron was –0.1 kg vs 9.4 kg for placebo.
AJMC article – FDA Approves Oral Semaglutide as First GLP-1 Pill for Weight Loss (Open access)
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Global race heats up for weight-loss drug pill