Bariatric surgery vs GLP-1s: GERD risk
Propensity-matched analysis of over 80,000 patients reveals bariatric surgery nearly doubles five-year esophageal complication rates compared with GLP-1 RA therapy.
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11/05/2025
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by Kerri Miller
A large propensity-matched cohort study presented at the American College of Gastroenterology 2025 Annual Scientific Meeting in Phoenix revealed significant differences in esophageal complications between bariatric surgery and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy for weight loss.
Bariatric surgery—particularly sleeve gastrectomy—nearly doubled the five-year risk of de novo GERD, esophagitis, and Barrett esophagus compared with GLP-1 RA therapy and was associated with greater need for endoscopic evaluation and acid-suppression therapy.
Himsikhar Khataniar, MD, and fellow researchers from Allegheny General Hospital in Pittsburgh, PA, and collaborating institutions, analyzed data from the TriNetX U.S. Collaborative Network. They identified adults with a body mass index greater than or equal to 30 kg/m² who either initiated FDA-approved weight-loss GLP-1 RA therapy (liraglutide, semaglutide, or tirzepatide) or underwent sleeve gastrectomy or Roux-en-Y gastric bypass from 2015 to 2020. While tirzepatide is a dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist, researchers grouped it under GLP-1 RAs.
Exclusions included prior GLP-1 RA exposure, previous bariatric surgery, or any history of GERD, esophagitis, Barrett esophagus, esophageal cancer, scleroderma, pregnancy, or intensive-care admission. Propensity-score matching balanced 47 demographic, clinical, medication, and laboratory variables between groups.
Before matching, 89,422 bariatric surgery recipients (mean age 49 years; 73% female) and 84,689 GLP-1 RA users (mean age 53 years; 56% female) were identified. Post-matching cohorts were well-balanced, with a mean age of 51 years and 65% female representation in each group.
Dr. Khataniar and colleagues assessed de novo reflux esophagitis, GERD, Barrett esophagus, esophageal cancer, esophagogastroduodenoscopy (EGD) utilization, and initiation of acid-suppression therapy.
Reflux esophagitis occurred in 0.7% of surgery patients versus 0.4% of GLP-1 RA users, representing nearly double the risk with surgery. GERD developed in 16.9% of surgery patients compared with 9.8% of GLP-1 RA users, reflecting an 88% increased risk with surgical intervention.
Barrett esophagus developed in 0.5% of surgery patients versus 0.2% of GLP-1 RA users, showing double the risk with surgery. Esophageal cancer remained rare in both groups, with no statistically significant difference between treatments.
EGD utilization was substantially higher among surgery patients at 8.8% versus 3.7% in the GLP-1 RA group. Proton-pump inhibitor initiation occurred in 29.4% of surgery patients compared with 20.8% of GLP-1 RA users. H₂-receptor antagonist prescriptions were required in 15.6% of surgery patients versus 11% of GLP-1 RA users.
Among individual interventions, tirzepatide users showed the lowest GERD incidence at 6.4%, whereas sleeve gastrectomy had the highest rate at 19.1% relative to GLP-1 RAs.
All researchers reported no relevant financial relationships.
Summary content
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.