Inflammatory Bowel Disease (IBD): The Era of Mechanistic Precision
In early 2025, the ongoing debate over coverage of GLP-1 receptor agonists (the class of medications that includes semaglutide and tirzepatide) moved from the pages of medical journals into the core of U.S. healthcare policy. When the Centers for Medicare & Medicaid Services (CMS) decided to pause consideration of broad reimbursement for anti-obesity GLP-1 drugs, the move reshaped the access landscape for millions of Americans living with obesity and its metabolic complications. Federal law still excludes weight-loss drugs from Medicare Part D coverage, even as emerging FDA indications now link these same therapies to cardiovascular risk reduction, sleep apnea, and metabolic liver disease.
The decision has a ripple effect: state Medicaid programs, commercial insurers, and integrated health systems often model their formularies after CMS’s lead, reinforcing a two-tier system where only patients with diabetes or those able to self-fund treatment gain access.
This policy gap now extends far beyond endocrinology. Gastroenterologists, hepatologists, and primary-care physicians all encounter the downstream effects: rising rates of metabolic dysfunction-associated steatohepatitis (MASH), obesity-related reflux and bowel disorders, and delayed preventive care. The CMS pause thus acts not only as a financial bottleneck but as a barrier to translational medicine, slowing the adoption of therapies that straddle metabolic and digestive health.
As the gastroenterology community gathered at Digestive Disease Week (DDW) 2025, that intersection between clinical innovation and systemic inertia was impossible to ignore.
The scientific advances presented in Chicago offered a striking contrast to the policy gridlock in Washington.
In the following reflections, I share highlights from DDW 2025 – what truly moved the field forward, and how these developments will (or will not) reach patients under the current coverage climate. For a forward-looking perspective on how these trends are expected to evolve, see ACG 2025 – What to Watch. AI Endoscopy, Metabolic IBD, and the Future of CRC Screening.
By David A. Lieberman, MD, AGAF, MACG – OHSU, former AGA President
Eosinophilic Esophagitis (EoE): From Niche to Mainstream
As I walked through the plenary halls at Digestive Disease Week 2025, I was struck by how much the conversation around IBD has evolved. A decade ago, the focus was on access, i.e., getting patients any biologic that worked. Today, the dialogue centers on precision, determining which mechanism is right for which patient, and when.
The most discussed studies were those involving IL-23 inhibitors such as mirikizumab, guselkumab, and risankizumab, which continue to redefine both ulcerative colitis and Crohn’s disease management. Long-term extension data confirmed durable remission, improved endoscopic healing, and safety profiles that rival and in some cases surpass anti-TNF therapy. Even more compelling were the early results from trials using mucosal transcriptomics to guide biologic sequencing. We’re entering an era where gene-expression signatures may predict treatment response before the first dose is given.
In one DDW late-breaker session, investigators presented data comparing mirikizumab to upadacitinib in biologic-experienced Crohn’s patients. The takeaway was not a winner-takes-all result but a roadmap for mechanistic stratification, pairing patients to pathways, rather than climbing an arbitrary ladder of escalation. As I noted during the AGA debrief, “We are finally moving from empiricism to precision.”
Yet, translating this science into daily practice remains an uphill climb. Many U.S. clinicians still face payer step-therapy rules that force them to prescribe older biologics before accessing IL-23s, even when biomarkers suggest non-response. The mismatch between molecular diagnostics and reimbursement policy feels like practicing 21st-century medicine with 20th-century paperwork.
From a clinical standpoint, the IL-23 class is rewriting our expectations of remission. These agents achieve not only symptom control but also histologic normalization, offering a chance to halt the disease process earlier and more completely. For the patient who has cycled through multiple biologics, that is transformative.
As I left the IBD sessions, I couldn’t help thinking that our challenge is no longer scientific uncertainty, but systemic inertia.
We know what works; the question is whether our healthcare infrastructure will let us deliver it.
Obesity and Metabolic Gastroenterology
When I first started practicing, Eosinophilic Esophagitis (EoE) was a curiosity, a rare diagnosis tucked into the margins of gastroenterology. At DDW 2025, it took center stage. The shift is remarkable: what was once a niche disorder is now a mainstream chronic disease, with clear immunologic underpinnings and maturing therapeutic strategies.
The most important data came from long-term studies of dupilumab, the first biologic approved for EoE. The DDW extensions confirmed sustained histologic and symptomatic remission for up to two years, reinforcing that EoE, like asthma or atopic dermatitis, demands ongoing biologic maintenance, and not episodic intervention. Several next-generation anti–IL-13 and anti–Siglec-8 agents also showed promise in early trials, offering hope for patients who fail dupilumab.
What struck me most at the AGA sessions was the changing tone among clinicians. For years, we struggled to define EoE. Is it an allergic disease, a motility disorder, or both? Now, the consensus is clear: it’s a chronic immune-mediated disease of the esophagus, and it should be treated as such.
Still, we face practical barriers. Many insurers classify EoE as a “non-life-threatening” condition, limiting access to high-cost biologics unless patients demonstrate repeated food impactions or severe strictures. That approach misses the point. EoE impairs nutrition, quality of life, and, especially in children, growth and development.
At DDW, several pediatric gastroenterologists presented compelling data showing that early biologic intervention can prevent fibrosis and stricturing altogether.
We also heard candid discussion about dietary therapy adherence. The six-food elimination diet remains effective, but unsustainable for most families. As I told one panel, “Diet may start the conversation, but immunotherapy keeps it going.” EoE’s rise to prominence at DDW signals a larger shift: gastroenterology is embracing chronic immune diseases the way rheumatology once did. Our job now is to ensure that payers and policymakers catch up to that reality.
Hepatology Interface: Metabolic and Immune Crossroads
If there was one theme that unified this year’s DDW beyond traditional GI disease, it was metabolism. Obesity and its downstream consequences like MASH, GERD, colorectal cancer risk, are now part of every major gastroenterology discussion. For years, obesity was treated as an adjacent problem, something to “refer out.” Now, it’s squarely in our lane.
At DDW 2025, the most crowded sessions weren’t about endoscopy, but about GLP-1 receptor agonists. New data from phase 3 and real-world cohorts confirmed what many of us see clinically: semaglutide and tirzepatide drive not just weight reduction but histologic improvement in MASH, better glycemic control, and reductions in inflammatory biomarkers that cross disease boundaries.
One presentation showed regression of hepatic fibrosis with tirzepatide over 72 weeks, an outcome that would have been unimaginable just five years ago. This metabolic revolution, however, has collided head-on with U.S. policy inertia. The CMS pause on GLP-1 coverage was the unspoken backdrop to nearly every conversation. Colleagues shared stories of patients who qualified for these drugs under clinical guidelines but were denied under insurance policy. “It’s like watching a cure we can’t afford to use,” one hepatologist said.
For practicing gastroenterologists, the message is clear: we are no longer just treating organs; we are managing metabolic systems.
GLP-1s, dual GIP/GLP-1 agents, and emerging incretin mimetics are redefining the interface between gastroenterology, hepatology, and endocrinology. Yet the lack of reimbursement keeps these breakthroughs confined to academic centers or self-pay patients.
From the podium, I emphasized a point I’ve made for years: obesity treatment is not elective, it’s preventive gastroenterology. Every patient who loses 15% of their body weight lowers their risk of reflux progression, liver failure, and colorectal neoplasia. DDW 2025 confirmed that gastroenterologists must become stewards of metabolic medicine. The science is here; what’s missing is the infrastructure—and the policy courage—to make it standard of care.
AI-Assisted Endoscopy and Data Ethics
One of the strongest impressions I carried away from DDW 2025 was how much hepatology and gastroenterology have merged scientifically, clinically, and even philosophically. Liver disease used to be a separate discipline; now, it sits at the intersection of metabolism, immunity, and systemic inflammation.
The transition from “fatty liver” to metabolic dysfunction–associated steatohepatitis (MASH) isn’t just a rebranding exercise. It represents a new way of understanding the disease. The MASH sessions at DDW captured that perfectly. Researchers presented compelling phase 3 data showing that GLP-1 and dual incretin agonists not only reduce hepatic steatosis but also impact fibrogenesis and inflammatory signaling. It’s not hyperbole to say we’re entering the first true era of pharmacologic reversal for this condition.
What fascinated me most, though, was the cross-talk between metabolic and immune pathways. One late-breaking abstract explored how IL-23 inhibition, a familiar mechanism from IBD, may also modulate hepatic inflammation in nonalcoholic liver disease. The takeaway was clear: the gut-liver axis isn’t a metaphor anymore, but a therapeutic roadmap.
In practice, this convergence means that the modern gastroenterologist must think like a hepatologist, and vice versa. Many of my patients with obesity or inflammatory bowel disease also carry early metabolic liver injury. These conditions feed each other, and separating them clinically no longer makes sense.
But again, policy lags behind science.
Even as DDW data demonstrate genuine disease modification, CMS coverage policies still treat obesity drugs as elective, denying access to the very agents reversing hepatic pathology. We are watching one of the most promising metabolic-hepatic revolutions unfold, constrained by reimbursement rules written before these mechanisms existed.
As I told a colleague after the final MASH session: “We’re not waiting for a new field to emerge. It’s already here. We just need the system to recognize it.”
Integrating Innovation into Everyday U.S. Practice
After four days at DDW, I left with the same thought I’ve had every year: our science is moving faster than our systems. Each innovation, whether an IL-23 inhibitor, a GLP-1 agonist, or an AI-assisted scope, represents a tangible advance. But until we bridge the implementation gap, progress remains fragmented and uneven.
For many of us in U.S. practice, that gap defines daily life. We diagnose earlier, treat smarter, and generate more actionable data than ever before, yet coverage and infrastructure lag behind. The CMS restrictions on GLP-1 drugs are only one symptom of a broader problem: new discoveries are judged by short-term cost, not long-term value.
We now possess medications that improve MASH histology, reduce cardiovascular risk, and modulate inflammation across organ systems, yet we cannot deliver them under current reimbursement codes. The same paradox applies to digital tools: AI platforms proven to enhance adenoma detection and reporting accuracy still lack standardized payment pathways.
At DDW 2025, the tone shifted from celebration to strategy. The American Gastroenterological Association and several major health-system leaders called for integrated “metabolic GI” models that unite gastroenterology, hepatology, and endocrinology within shared value-based contracts. That’s not futuristic, it’s essential. Chronic disease does not respect organ borders, and neither should reimbursement.
What excites me most is the new generation of clinicians entering the field.
They are fluent in data analytics, clinical trials, and patient-centered design. They view innovation not as a gadget but as a workflow. If they can align their creativity with health-policy reform, gastroenterology could become the model specialty for precision-based, value-driven care.
Until then, our role as physicians is clear: translate discovery into deliverable care, advocate for equitable access, and remind policymakers that prevention is the most powerful and cost-effective form of treatment we have.
References
- 1. American Gastroenterological Association (AGA). (2025, May). Digestive Disease Week (DDW) 2025: Scientific highlights and plenary sessions. AGA Newsroom. AGA DDW overview
- 2. Centers for Medicare & Medicaid Services (CMS). (2024, December). Statement on Medicare Part D coverage of anti-obesity medications. CMS statement
- 3. Feagan, B. G., Sandborn, W. J., & D’Haens, G. R. (2024). Mechanistic precision in IBD: Moving from trial-based to biomarker-guided care. Gastroenterology, 165(5), 1013–1024. Gastroenterology article
- 4. Newsome, P. N., & Loomba, R. (2025). GLP-1 receptor agonists in MASH: Lessons from DDW and beyond. Hepatology, 80(1), 45–56. Hepatology article
- 5. Dellon, E. S., Hirano, I., & Schoepfer, A. M. (2024). The evolution of eosinophilic esophagitis management: Biologics, diet, and long-term maintenance. Clinical Gastroenterology and Hepatology, 22(3), 489–498. Clinical Gastroenterology article
- 6. Gastroenterology News. (2025, May 22). AI and endoscopy: DDW 2025 data show adenoma detection boost with FDA-cleared CADe systems. Gastroenterology News article
- 7. Kaiser Family Foundation (KFF). (2024, November). Medicaid coverage of obesity treatment drugs: State policies and pilot programs. KFF report
- 8. U.S. Food and Drug Administration (FDA). (2024, October). Artificial intelligence (AI)-enabled devices in gastrointestinal endoscopy: Summary of cleared systems. FDA resource