Dear colleagues,

Two years ago, we asked whether gastroenterologists were ready to take the lead in managing obesity. Since then, the landscape has shifted dramatically. Landmark pharmacologic advances—particularly GLP-1 receptor agonists—have become household names, and the conversation around weight loss now permeates nearly every corner of medicine. But with broader adoption comes new questions: Should we favor medications over procedures? How durable are these interventions? Can endoscopic sleeve gastroplasty (ESG) and pharmacotherapy work together? And where do we, as gastroenterologists, fit in?

In this issue, Dr. Marianna Papademetriou makes a strong case for embracing medical weight loss tools—including GLP-1 RAs—as a natural extension of practice, grounded in physiology, patient need, and existing expertise. Dr. Eric Vargas and Dr. Dan Maselli counter with an equally compelling defense of ESG, arguing that endobariatrics remains a vital, underused tool—and that it’s time for greater integration, not replacement.

As this field continues to evolve, these commentaries remind us that effective weight loss care requires a multidisciplinary, patient-centered approach, using an ever-growing armamentarium of endoscopic and pharmacologic treatments. We hope these perspectives help guide how you approach weight loss management in your own practice. As always, we welcome your feedback and real-world experience, and you can join the conversation on X at @AGA_GIHN.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News. 

ESG: An effective complement to the pharmacologic era

By Eric J. Vargas, MD, MS, D-ABOM, and Dan Maselli, MD, D-ABOM

The evolving role of ESG

Over the past decade, ESG has matured from an innovative concept into a safe, reproducible, and durable intervention for weight loss. Initially introduced as a minimally invasive alternative to surgical sleeve gastrectomy, ESG has steadily refined its technique, safety, and outcomes. Today, it occupies a unique position within the continuum of obesity care, bridging the gap between lifestyle interventions, pharmacotherapy, and surgery.

As obesity care enters a robust pharmacologic era defined by increasingly potent gut-hormone agonists, ESG offers versatility as a durable anatomical therapy for a variety of patients: those seeking alternatives to long-term medications, those seeing weight return after medication cessation, and those aiming for surgical-level health benefits through complementary therapy that combines ESG with medications. This reflects a broader shift toward flexible, patient-centered strategies that address the chronic and multifactorial nature of obesity.

Incretin-mimetic revolution 

GLP-1 receptor agonists and other incretin mimetics has transformed the obesity landscape. Their efficacy has enabled many patients to achieve meaningful weight loss, often for the first time in their lives, and has dramatically increased public awareness on obesity as a treatable condition.

However, real-world practice has revealed a predictable challenge: weight recurrence when medications are reduced or discontinued. Interruptions due to cost, insurance variability, supply shortages, intolerable side effects, pregnancy planning, or patient preference frequently trigger weight regain. Across the endobariatrics landscape, we increasingly encounter patients who achieved substantial weight loss from medications but now seek a durable solution as they reconsider, taper, or discontinue lifelong pharmacotherapy. For many, losing progress after investing deeply in their weight loss-journey can be profoundly discouraging.

ESG as a stabilizing partner

Here is where ESG demonstrates its greatest value in the pharmacologic era of obesity management. Unlike medications that rely on continuous use, ESG provides a durable anatomical change that reinforces satiety, reduces gastric volume, and supports long-term behavior modification. The literature and clinical experience repeatedly show adherence to GLP-1 based medications does not extend beyond one to two years for the majority of patients with obesity. As leaders of the Metabolic & Bariatric Endoscopy Program at Mayo Clinic Rochester, we have seen firsthand how ESG mitigates the rebound that consistently follows pharmacotherapy tapering. Patients who undergo ESG while on GLP-1 therapy, and later reduce or discontinue medication, experience far more stable long-term weight trajectories compared with those who taper medications alone.

The combination is synergistic: pharmacotherapy initiates weight loss, and ESG anchors it. This partnership improves outcomes, reinforces adherence, and reduces the anxiety many patients feel about stopping obesity medications.

Looking ahead: The multi-agonist era

The next generation of pharmacologic agents promises even greater efficacy. Retatrutide, a triple GIP/GLP-1/glucagon agonist, has demonstrated early results approaching surgical-level weight loss. These developments are remarkable and welcomed. Yet all gut-hormone agonists share core limitations: they require ongoing use, tolerability varies, costs and coverage remain uncertain, discontinuation consistently leads to weight and comorbidity recurrence.

These emerging therapies will only increase the relevance of ESG. As medications become more potent, the need for a stabilizing anatomical intervention that sustains weight loss beyond active pharmacotherapy will grow. ESG provides the foundation, functioning as a minimally invasive, long-term anchor in a multimodal treatment strategy.

Flexibility and surgical compatibility

A key advantage of ESG is its versatility. Although typically performed once, ESG can be safely repeated in patients with gastric dilation or partial weight recurrence—findings consistent with obesity as a chronic, relapsing disease with multiple redundant pathways. In our practice, reinforcing a previously placed sleeve has restored physiologic benefit in selected patients, a capability unique among minimally invasive interventions.

ESG also integrates well with bariatric surgery. It can be performed after removal of an adjustable gastric band or to revise a dilated surgical sleeve. Conversely, ESG can enhance pre-operative feasibility in patients with high BMI, significant metabolic disease, or inadequate response to medications who are preparing for bariatric surgery. Patients who undergo ESG before surgery often find the eventual transition to surgery both physically and psychologically easier. For many, progressing from medication to ESG to surgery feels more intuitive than moving directly from medication to a surgical intervention.

Durability, metabolic effects, and endorsement

Long-term data further validate ESG’s role in comprehensive obesity management. Five-year studies now demonstrate sustained 10-15% total body weight loss, low rates of adverse events(<1%), and durable improvements in comorbid conditions such as type 2 diabetes, MASLD, and cardiovascular disease. These findings align with the IFSO Bariatric Endoscopy Committee’s recent evidence-based review endorsing ESG as a validated, durable, and integral therapy.

Expanding access and infrastructure

ESG’s utility is further strengthened by emerging policy and infrastructure. A dedicated Category I CPT code for ESG will take effect in January 2026, reflecting mainstream recognition of the procedure as an evidence-based therapy. Several private insurers have already added ESG as a covered benefit, including Mayo Clinic, expanding access and helping narrow equity gaps for patients who may not have the means or desire to remain on lifelong pharmacotherapy.

Within our program, we have observed how coordinated follow-up, multidisciplinary care, and structured training platforms create sustainable ESG practices. These elements will be essential to scaling ESG responsibly across diverse clinical settings.

ESG and the future of metabolic endoscopy

More than a decade into its use, ESG has clearly proven the value of endoscopic gastric remodeling for patients with obesity and related metabolic disease. Yet this is only the beginning. As ESG is increasingly paired with incretin-based medications to achieve weight-loss outcomes approaching bariatric surgery, its role as a platform for combination metabolic endoscopic therapies is becoming clear. Emerging approaches—including gastric fundal mucosal ablation to reduce ghrelin and duodenal mucosal ablation to improve insulin resistance—offer new, targeted ways to modulate appetite and metabolism. Together, these mucosal interventions and ESG could evolve into a single-stage, incisionless combination procedure delivered safely in the ambulatory setting at experienced endobariatric centers.

Conclusion

After following patients for many years, it is clear that ESG offers durability, flexibility, and compatibility with both pharmacotherapy and surgery—attributes increasingly important in a landscape shaped by potent incretin-based and multi-agonist medications. For some patients, ESG will serve as a meaningful alternative to medications; for many others, it will enhance and stabilize pharmacotherapy-induced weight loss. As access expands, ESG will remain a central tool for long-term, sustainable obesity management in the pharmacologic era.

Dr. Vargas is an interventional endoscopist and assistant professor of medicine at Mayo Clinic Rochester.

Dr. Maselli is a gastroenterologist in Atlanta, GA, practicing at True You Weight Loss.

Disclosures

Dr. Vargas has received research support from Boston Scientific and Phillips Healthcare.

Dr. Dan Maselli has conducted prior consulting for Apollo Endosurgery/Boston Scientific.

References

1. Dayyeh BKA et al. Obesity Surgery. 2024;34(12):4318-4348.

2. Lahooti A et al. Gastrointestinal Endoscopy. 2025;102(1):26-36.

3. Berg S et al. Obes Rev. 2025 Aug;26(8):e13929.

All of Your Patients are Already on GLP1s

By Marianna Papademetriou, MD

GLP-1RAs mark transformational shift in obesity care

In our medical careers, the approval and widespread uptake of incretin mimetics, more commonly GLP-1RAs, represent a turning point in obesity management. Historically, the management of obesity relied on lifestyle modifications and limited pharmacologic options, both of which offered modest results and were difficult to sustain long term. Now, with the advent of GLP-1RAs—recently FDA-approved for obesity, metabolic associated steatohepatitis (MASH), cardiac disease, and sleep apnea—has fundamentally altered this paradigm. Gastroenterologists are uniquely positioned to lead the integration of GLP-1 therapies into our established practices.

We have had safe, effective, and durable treatment through bariatric and metabolic surgery for decades. In the last 10 years, endoscopic bariatric and metabolic procedures (EBMTs) have also been developed and evolved to include a variety of options to tailor to individual patient goals and needs.¹ However, uptake of surgical procedures has stagnated at around 270,000 per year, representing a fraction of eligible US patients.²

EBMTs likewise, are still limited geographically and have not historically been covered by commercial insurance, although we are on the verge of this changing with the new CPT codes in 2026. Notably, because we know obesity is chronic, relapsing, and significantly under-treated, there is clearly need for an all-hands-on-deck approach with available modalities.

I’ll discuss three main reasons why gastroenterologists are already ideally positioned to prescribe and support the use of GLP1-RA as part of this evolving landscape. First, many patients are already on GLP1s, with or without the support of clinicians with expertise in this field and may be better served with thoughtful clinician guidance. Additionally, many GI conditions can improve with the significant weight loss achieved on GLP1RA. Third, the most common side effects are GI related; and, therefore, gastroenterologists are primed to help with management and personalization.

Widespread patient adoption of GLP-1RAs

A recent Kaiser Family Foundation poll found that one in five US adults report ever being on a GLP1-RA.³ In 2024, when both semaglutide and tirzepatide were on the national drug shortage list, a large compounding industry developed to fill the gap. Digital health care delivery start-ups materialized to provide patients with prescriptions with limited required personal health data. Access barriers, from cost to health-care bias, were removed as patients could order medications from the comfort of their homes. Reddit and Facebook support groups appeared for patients to counsel each other. Many were successful in reaching their weight-loss goals. However, with time we’ve accumulated more experience for optimizing care. Patients may benefit even further from gastroenterologist guidance through the process to help counter lean muscle mass and bone loss, avoid nutritional deficiencies, and titrate medications for comorbidities.⁴ Patients have shown they want to be on these medications; as gastroenterologists we should meet patients where they are with the expertise and empathy that can improve outcomes.

Expanding clinical indications

GLP1-RAs are now approved for more indications beyond treatment of overweight and obesity. Semaglutide was recently approved for metabolic associated steatohepatitis (MASH). Tirzepatide is approved for the treatment of sleep apnea.  While not approved specifically for these conditions, obesity is an independent risk factor for the development of many GI cancers. Among patients with yype 2 diabetes, GLP-1 RAs show significant risk reductions for several obesity-associated GI cancers when compared to insulin: colorectal (46% reduction), pancreatic (59% reduction), liver (53% reduction), gallbladder (65% reduction), and esophageal (40% reduction).⁵ As the clinicians who are often diagnosing these conditions, gastroenterologists should also be at the forefront of prescribing medications that help reduce risks.

Well known profile of side effects

Rather infamously, GLP1-RAs are associated with a variety of GI side effects. Curiously, I have never encountered a class of medications where patients are more willing to tolerate said side effects and persevere than when prescribing GLP1-RAs. Dose escalation to levels where significant weight loss is achieved also includes a transitional period where patients may experience nausea, vomiting, reflux, dyspepsia, diarrhea, or constipation. Gallstones and biliary disease are also seen. Some patients require longer lead in periods before doses are escalated, and some patients reach their weight endpoints at doses lower than those studied in clinical trials. These side effects can often be managed medically using the same techniques, counseling, and medication arsenals that gastroenterologists have honed for years.

GLP1-RAs are here to stay.  As the therapeutic landscape continues to evolve, it is incumbent upon gastroenterologists to embrace evidence-based use of GLP-1RAs, coordinate multidisciplinary care to maximize patient outcomes, and optimize management of adverse effects. Future research is needed to best customize long-term therapy for efficient weight maintenance and cost-effectiveness.

Dr. Papademetriou is an assistant professor at the VA Medical Center in Washington, DC.

References

1. Jirapynio et al. Gastrointest Endosc. 2024 Jun;99(6):867-885.e64.

2. https://asmbs.org/resources/estimate-of-bariatric-surgery-numbers. Access date: 12/1/2025.

3. KFF Health Tracking Poll (October 27-November 2, 2025). Access date: 12/1/2025.

4. Mozaffarian et al. Obesity (Silver Spring). 2025 Aug;33(8):1475-1503. 

5. JAMA Network Open. 2024 Jul 1;7(7):e2421305. doi: 10.1001/jamanetworkopen.2024.21305.