On 22 December 2025, the US Food and Drug Administration (FDA) approved the Wegovy® pill (oral semaglutide 25 mg tablet) as the first oral GLP-1 receptor agonist for chronic weight management. Indications include reduction of excess body weight and long-term maintenance in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity, when used with reduced-calorie diet and increased physical activity. Additionally, it is approved to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight.
The VALAD trial was a phase 2, randomized, double-blind, placebo-controlled clinical trial conducted at academic medical centers in the United States. A total of 120 participants (mean age approximately 71 years) with early-stage AD or mild cognitive impairment with biomarker evidence of AD pathology, and seropositivity for HSV-1 or HSV-2, were enrolled and randomized 1:1 to valacyclovir or placebo. Participants received oral valacyclovir (up to 4 g daily, titrated based on tolerability) or matching placebo for 78 weeks (18 months).
Approval was supported by the OASIS phase 3 programme, including the pivotal OASIS 4 trial—a 64-week, randomised, placebo-controlled study in 307 adults with obesity or overweight and comorbidities. Using the treatment policy estimand (effect regardless of adherence), mean weight loss was approximately 13.6–14%; with the trial product estimand (assuming full adherence), it reached 16.6%, comparable to the ~15% observed with injectable Wegovy® in prior trials. One in three participants achieved ≥20% weight loss. Data from the SELECT cardiovascular outcomes trial further supported the CV risk reduction benefit. The safety profile aligned with known semaglutide effects, primarily gastrointestinal adverse events, with no new signals identified.
This approval introduces a convenient daily oral alternative, potentially improving accessibility and adherence for patients averse to injections. Novo Nordisk anticipates US launch in early January 2026, with submissions pending at the European Medicines Agency and other regulators. The Wegovy® pill expands treatment options in the growing GLP-1 class, addressing unmet needs in obesity management.
