Timothy Garvey, MD, is a professor of medicine at the Univeristy of Alabama at Birmingham. 

W. Timothy Garvey, MD

Obesity as a Disease: Reanalyzing and Reformatting How Excess Adiposity is Addressed In and Out of Clinics

 is among the most devastating chronic diseases in the world, with 1.6 million premature deaths from 

 connected back to excess adiposity every year. Current prediction models expect more than 2.9 billion adults worldwide to be living with a high body mass index (BMI) by 2030. What’s more, recent analyses have shown that 2/3 of all countries have ≤1 policy in place to address the epidemic.

Despite widespread awareness of both the condition and its potential comorbidities, combating obesity has thus far been an uphill battle. Its prevalence, combined with the immense social stigma surrounding the disease, has put patients in the unfortunate position of having to fight not only obesity itself, but also the assumptions and beliefs surrounding it. The American Diabetes Association (ADA) has released guidelines on addressing the bias and stigma around obesity and weight, suggesting that clinicians receive training on these biases to improve care for patients. This training emphasizes privacy and sensitivity during anthropometric measurements and asking permission before discussing weight and obesity with patients.

However, for every roadblock in the path to wellness, great strides have been made in obesity care over the last few years. From the advent of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide and tirzepatide to the broad adoption of the view of obesity as a multi-disciplinary condition, clinicians have begun to turn the tide against the disease. Prescription medications and the advancement of bariatric surgery have bolstered the effectiveness of major lifestyle interventions in managing excess adiposity. And the shifting perception of obesity as a chronic disease rather than a sign of weakness or laziness has only just begun to overhaul the way the condition is addressed.

Today, obesity is largely approached not as a risk factor but as a separate disease influencing all parts of the body. The recently proposed cardio-kidney-metabolic framework spotlights the interconnection between cardiovascular, renal, and metabolic diseases, among which obesity plays a substantial role. Clinicians have begun collaborating more often and more significantly in addressing these comorbidities, heading obesity off at each pass.

 editorial team spoke with 3 major voices in the world of obesity care, catching up with recent advancements, addressing ongoing challenges, and providing expert insights and advice.

Editor’s Note: Garvey reports disclosures with Boehringer-Ingelheim, Novo Nordisk, Eli Lilly, Merck, Neurovalens, Fractyl Health, and others. Cohen and Vedala report no relevant disclosures.

Lobstein T, Powis J, Thompson R, Jackson-Leach R. World Obesity Atlas 2025. 

https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2025

Bannuru RR; Professional Practice Committee. Weight stigma and bias: standards of care in overweight and obesity-2025. 

. 2025;13(Suppl 1):e004962. Published 2025 May 16. 

Moura AF, Pecoits-Filho R. Cardio-kidney-metabolic (CKM) framework: A nephrologist's perspective. 

. 2025;70(special 1):e250405. Published 2025 Nov 28. 

Videos

This World Obesity Day, catch up on major paradigm shifts in the diagnosis, discussion, and treatment of obesity, one of the world’s most devastating chronic diseases.

Oral Semaglutide and the Future of GLP-1 Obesity Treatment, With Timothy Garvey, MD

As highly effective GLP-1-based therapies continue to transform obesity care, their growing use has sharpened attention on safety, patient selection, and the importance of active clinical oversight. While the US Food and Drug Administration (FDA) approval of oral semaglutide (Wegovy) expands access and choice, it also underscores the need for careful risk assessment and long-term management strategies as clinicians incorporate these agents into routine practice.

The December 22, 2025, approval was based on the results from the phase 3 OASIS 4 clinical trial, a 64-week medical study that included 307 adults with obesity or overweight with ≥ 1 weight-related comorbidity, without diabetes. In addition to the oral formulation’s proven efficacy for weight loss, OASIS 4 data showed the most common adverse reactions were similar to those previously seen in clinical trials with semaglutide injection 2.4 mg, including nausea, diarrhea, and vomiting.

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, emphasizes that established contraindications remain unchanged across GLP-1 formulations but notes that the therapy is not suitable for patients with contraindications like a history of medullary thyroid carcinoma or acute pancreatitis. He also highlights gallbladder disease as an important clinical consideration, noting that rapid or substantial weight loss, regardless of modality, is associated with increased gallstone risk, with GLP-1 therapies appearing to amplify this effect.

Beyond traditional safety concerns, Garvey calls attention to a more nuanced challenge emerging in real-world practice: excessive weight loss in highly responsive patients. While many individuals benefit substantially from GLP-1–induced weight reduction, some continue losing weight beyond a healthy threshold.

“Some patients just keep losing weight and losing weight, and they can feel tired and run down and listless, and their cognition can even be a little cloudy,” he said. “They don't socialize as well… Some of these patients will say ‘Dr Garvey, I'm losing too much weight. I have to slow down. My friends tell me I don't look good. I look older, I'm tired, I don't have the energy to get things done anymore.’ Other patients will have those same symptoms, but they're kind of enthralled or addicted to the weight loss, and they'll just want to keep losing weight and losing weight. They don't have a perspective on this, and this is where a healthcare professional comes in.”

Adherence considerations also differ between formulations. Oral semaglutide requires daily dosing under specific conditions to optimize absorption, including administration with water on an empty stomach before food intake. Garvey notes that while this regimen may appear burdensome, most patients adapt readily, particularly when oral therapy aligns with their preferences.

Looking ahead, Garvey frames oral semaglutide as part of a rapidly advancing therapeutic continuum. Dual- and triple-agonist agents targeting multiple metabolic pathways are already demonstrating weight loss approaching that of bariatric surgery in clinical trials. However, he cautions that greater potency does not equate to universal need. Increasingly, clinicians are finding success with submaximal dosing, emphasizing individualized treatment rather than maximal weight reduction.

Despite recent progress, Garvey stressed that long-term experience with these second-generation agents remains limited.

“We've only had these medicines since 2021, so we don't have long-term experience. We don't know what the long-term effects will be with bone loss and muscle loss and perhaps 10 years later, more falls and fractures. We just don't know,” Garvey said. “We need a longer term experience, and we need to develop evidence-based strategies for maintaining patients on these medications, promoting adherence, and make sure they take medicines for this chronic disease so they can maintain the health benefits and the weight loss. We're not there yet, so we still have a long way to go.”

Editors’ Note: Garvey reports relevant disclosures with 

Boehringer-Ingelheim, Novo Nordisk, Eli Lilly, Merck, Neurovalens, Fractyl Health, and others.

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

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

With the FDA approval of oral semaglutide, Garvey weighs safety, oversight, and the future direction of GLP-1 weight management therapy.

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.

Garvey reflects on the recent FDA approval of oral semaglutide (Wegovy) as the first GLP-1 pill for weight loss.

Welcome back to Diabetes Dialogue at ADA 2025!

Diabetes Dialogue: REDEFINE 1 and REDEFINE 2, with Timothy Garvey, MD, and Melanie Davies, MD

85th Scientific Sessions of the American Diabetes Association (ADA 2025)

, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, take a deep dive into the REDEFINE 1 and REDEFINE 2 trials with trial investigators W. Timothy Garvey, MD, of University of Alabama at Birmingham, and Melanie Davies, MD, of the University of Leicester.

REDEFINE 1 was a 68-week, phase 3a trial enrolling over 3400 adults without diabetes but with obesity or overweight and at least one comorbidity. Participants received once-weekly CagriSema, semaglutide alone, cagrilintide alone, or placebo alongside lifestyle intervention.

Key outcome: CagriSema led to a mean weight loss of 20.4%, vs 3.0% with placebo.

Over 50% of participants on CagriSema reached a non-obese BMI.

Gastrointestinal side effects were common (80%), but mostly mild to moderate.

REDEFINE 2 enrolled 1206 adults with type 2 diabetes and overweight or obesity, randomized to CagriSema or placebo for 68 weeks.

Key outcome: CagriSema led to 13.7% mean weight loss, vs 3.4% with placebo.

73.5% achieved an HbA1c ≤6.5% vs 15.9% on placebo.

Significant improvements were seen across all weight loss and glycemic endpoints.

The speakers also highlight the agent’s favorable side effect profile, flexibility in real-world dosing, and benefits in body composition and physical function. Garvey emphasizes the shift toward complication-centric obesity care, underscoring the need for clinician-guided treatment beyond online prescription models.

The conversation closes with a look ahead to REDEFINE 3—a cardiovascular outcomes trial including patients with and without diabetes—and other ongoing studies in the REDEFINE and REIMAGINE trial programs.

Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

Relevant disclosures for Garvey include Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Epitomee, Pfizer Inc., and Neurovalens. Relevant disclosures for Davies include Abbie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GSK, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, and Zealand Pharma.

Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. 

Davies MJ, Bajaj HS, Broholm C. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. 

Podcasts

Explore groundbreaking findings from the REDEFINE trials on CagriSema's impact on weight loss and diabetes management at ADA 2025.

W. Timothy Garvey, MD

Articles