How Oral GLP-1 Therapy Fits Into the Evolving Obesity Treatment Landscape, With Timothy Garvey, MD

The US Food and Drug Administration approval of Novo Nordisk’s oral semaglutide (Wegovy) as the first GLP-1 receptor agonist pill for chronic weight management represents a notable evolution in a rapidly expanding obesity treatment landscape. As GLP-1-based therapies continue to reshape metabolic care, the availability of an oral option introduces new considerations around adherence, access, and long-term disease management for clinicians.

Injectable GLP-1 receptor agonists have demonstrated unprecedented efficacy in weight reduction and cardiometabolic risk modification, yet real-world use has highlighted persistent barriers. Discontinuation rates remain high, often driven by injection aversion, logistical challenges, or tolerability concerns.

In an interview with HCPLive, Timothy Garvey, MD, a professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham, noted that oral administration may help address some of these barriers by aligning treatment with patient preferences, which can be a critical determinant of long-term adherence in chronic disease care.

“Despite the fact that these GLP-1 based obesity medicines are really transformational, currently, we're really not treating this disease very well when you consider that after 1 year, over 50% of patients aren't taking the medicine anymore,” he explained. “We need strategies for longer term adherence, and when a patient is taking a medication in the form that they prefer, then predictably, there would be better adherence over time.”

Beyond preference, the oral formulation introduces practical advantages with implications for both domestic and global care delivery. Unlike injectable semaglutide, the oral version does not require refrigeration, reducing storage and travel-related challenges. Garvey notes this feature may be particularly impactful in regions with limited cold-chain infrastructure, where injectable therapies have been difficult to distribute at scale. As obesity prevalence continues to rise worldwide, improved flexibility in drug delivery could expand access to effective pharmacologic treatment.

Efficacy data supporting the approval also reinforce the clinical relevance of the oral option, with results from the OASIS 4 trial showing weight loss outcomes comparable to those reported in injectable semaglutide studies. In the 64-week phase 3 trial, patients who stayed on treatment with semaglutide experienced an average weight loss of ~17% and ~14% regardless of if patients stayed on treatment.

Gastrointestinal adverse events including nausea, vomiting, diarrhea, and constipation were consistent with the known GLP-1 class profile, underscoring that route of administration does not eliminate the need for careful dose escalation and patient counseling.

As prescribing options multiply, clinicians are increasingly tasked with matching therapies to individual patient needs rather than choosing a single dominant modality. Garvey emphasized that oral and injectable semaglutide should be viewed as complementary tools within a broader obesity management framework, with cost, access, and patient preference guiding selection.

“I hope that these medications are made available by healthcare professionals to the patients they're following, and not through online prescription services where there’s no meaningful evaluation or meaningful follow up. That's not how we treat a disease like this, and our patients deserve better than that,” Garvey said.

As obesity is increasingly recognized as a chronic, adiposity-based disease with multisystem implications, Garvey emphasizes that sustained clinical oversight remains essential, regardless of whether treatment is delivered by pill or injection.

Editors’ Note: Garvey reports relevant disclosures with Boehringer-Ingelheim, Novo Nordisk, Eli Lilly, Merck, Neurovalens, Fractyl Health, and others.

References

1. Brooks A. FDA Approves Semaglutide (Wegovy) Pill As First Oral GLP-1 for Weight Loss. December 22, 2025. Accessed December 24, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-pill-as-first-oral-glp-1-for-weight-loss

2. Kunzmann K. FDA Approves Semaglutide for Obesity Weight Management. June 4, 2021. Accessed December 24, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-obesity-weight-management