Oral Semaglutide: Pioneering Weight Loss with Cardiovascular Benefits

In the OASIS 4 trial, oral semaglutide 25 mg produced substantial weight loss and cardiometabolic gains in adults with overweight or obesity, offering a pragmatic, noninjectable option for long-term management.

The 64-week, randomized, double‑blind, placebo‑controlled phase 3 OASIS 4 trial enrolled adults with obesity or overweight plus at least one weight‑related comorbidity and excluded people with diabetes. Participants who adhered to treatment achieved a mean 16.6% weight reduction—the trial’s primary efficacy endpoint—a magnitude that meets clinically meaningful thresholds for obesity therapy and is comparable to existing injectable GLP‑1 agents in the studied cohort.

Alongside weight loss, there were improvements in cardiovascular risk markers and gains in daily physical function among treated participants. The scale of weight reduction is expected to drive downstream benefits—lowering blood pressure, improving lipid profiles and insulin sensitivity—which plausibly mediate the aggregated cardiometabolic signal. These concurrent cardiovascular changes strengthen the clinical relevance of treating cardiometabolic risk in patients without diabetes.

Tolerability was described as acceptable overall, with adverse events predominantly mild to moderate and most commonly gastrointestinal. Typical effects such as nausea and transient vomiting occurred and led to permanent discontinuation in a minority of participants, underscoring the need for anticipatory counseling and symptom‑management strategies during initiation and dose escalation.

Overall, the safety profile was reported to align with injectable semaglutide formulations, supporting oral use in appropriately selected patients with standard monitoring. And so clinicians should consider integrating the oral option into shared decision‑making, formulary discussions, and care pathways for eligible patients.

Taken together, the reported efficacy, concurrent cardiometabolic signal and manageable tolerability indicate oral semaglutide 25 mg can be a practical alternative for patients who prioritize an oral route while still achieving clinically meaningful weight and metabolic outcomes. Clinicians should embed patient preference in shared decision‑making, plan for monitoring of gastrointestinal tolerance and cardiometabolic markers, and engage formulary and access pathways to operationalize this option for appropriate patients.