Acute pancreatitis is not 'one-and-done'

"The reality is that while 96–98% of patients survive the acute event, a large proportion face clinically meaningful long-term pancreatic consequences that can be missed once they leave the hospital."

01/20/2026

by Doug Brunk

The first two years after acute pancreatitis (AP) are the critical window when both pancreatic morphology and endocrine function change most dynamically, interim results from an ongoing prospective study in Hungary showed.

“Acute pancreatitis (AP) is often treated like a ‘one-and-done’ hospitalization,” corresponding author Peter Hegyi MD, PhD, DSc, of the Institute of Pancreatic Diseases at Semmelweis University, Budapest, Hungary, told GI & Hepatology News. “The reality is that while ~96–98% of patients survive the acute event, a large proportion face clinically meaningful long-term pancreatic consequences that can be missed once they leave the hospital. In our cohort, by year 4 the combined burden of prediabetes and diabetes was very high, and the highest incidence of new endocrine deterioration clustered early. That matters because it gives clinicians a clear time horizon for follow-up rather than vague ‘as needed’ monitoring.”

In the Goulash-Plus study, published in Gastroenterology as a research letter, investigators at four centers in Hungary aimed to clarify the temporal course and predictors of both morphological and endocrine sequelae following AP. Reporting on 360 patients enrolled to date, they classified participants based on pancreatic morphology into AP, recurrent AP (RAP), early chronic pancreatitis (ECP), or chronic pancreatitis (CP) groups, and according to endocrine status into normal, prediabetes, or diabetes categories. Morphological and endocrine assessments were conducted at baseline and annually during follow-up.

The mean age of patients was 54.5 years and 43% were female. At baseline, 74.7% had a single AP episode, 11.9% had RAP, 6.9% had ECP, and 6.4% had CP. During follow-up, the proportion of patients with RAP, ECP, or CP more than doubled, from 25.3% at baseline to 55.1% at year four. Among patients with a single AP at baseline, 35.1% progressed to RAP, ECP, or CP by year four, with the most rapid morphological changes occurring within the first two years.

Endocrine dysfunction showed similar trends. While 59% of patients had normal glucose metabolism at baseline, the combined prevalence of prediabetes and diabetes reached 76.4% by year four. Notably, among patients with a single AP episode and normal baseline endocrine status, more than half (54.4%) developed prediabetes or diabetes by the fourth year. The most dynamic changes occurred in the first two years post-AP, with statistically significant annual increases in new-onset prediabetes and diabetes.

“What surprised me in the interim analysis was how sharply the curves moved early: both morphologic progression (toward recurrent AP/early chronic pancreatitis/chronic pancreatitis) and endocrine deterioration were front-loaded in the first two years, with a clear deceleration afterward,” Dr. Hegyi said. “Clinically, that’s a ‘lightbulb moment,’ because it suggests that if a patient remains stable through that early period, their subsequent risk trajectory may look different than we previously assumed.”

He further noted that the clinical implications of the findings to date are that AP should prompt a structured follow-up plan, particularly during the first two years. “Our data support (at minimum) annual assessment of endocrine status (e.g., oral glucose tolerance testing where appropriate) and consideration of imaging-based follow-up to detect morphologic progression during that early window,” Dr. Hegyi said. “Importantly, this approach is not about ‘testing everyone forever’; it’s about focusing attention when the signal is strongest and when early intervention, counseling, or referral is most likely to help.”

Dr. Hegyi acknowledged certain limitations of the study, including the interim nature of the findings. “Follow-up is ongoing, and observational data cannot prove causality,” he said. “Additionally, the optimal risk-stratification strategy (who needs which test, and how often) still needs refinement as the full cohort matures.”

The research was supported by the Hirshberg Foundation, Hungarian Ministry of Innovation and Technology, and the National Research, Development and Innovation Fund.

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In an interview with GI & Hepatology News, Philip Hart, MD, a gastroenterologist who is director of clinical research for the Division of Gastroenterology, Hepatology, and Nutrition at The Ohio State University, offered his thoughts on the study.

Why is this study important?

Dr. Hart: The paradigm of acute pancreatitis continues to evolve. Historically, it was considered a self-limited acute disease; studies, such as the present one, demonstrate it is an acute disease with important long-term sequelae. This prospective study focuses on recurrence and progression of pancreatitis (described here as morphologic progression) and changes in glycemic status.

Using prospective data, the investigators demonstrated a meaningful risk of clinical events within the first few years following hospitalization. Even amongst patients experiencing their first lifetime episode of acute pancreatitis, clinically meaningful risks were observed, including a 35% risk of recurrent acute pancreatitis at one year. And, over 75% of patients had prediabetes or diabetes by four-years of follow-up.

What are the potential clinical implications of the research?

Dr. Hart: Taken together, these findings support the growing consensus that clinical follow-up after hospital discharge is warranted for all patients with acute pancreatitis. This follow-up should include assessment for persistent symptoms, screening for diabetes (which is now endorsed by the American Diabetes Association), exocrine pancreatic dysfunction, and progression to chronic pancreatitis.

What additional research may be needed/what questions remain unanswered?

Dr. Hart: The investigators presented compelling trends in multiple aspects of disease progression for acute pancreatitis. Future studies are needed to identify clinical, radiographic, laboratory, and genetic markers that can identify individuals at highest risk for progression to enable tailored surveillance and early intervention efforts. The multicenter DREAM study (NCT06401577) in the United States is employing detailed metabolic testing (including standardized oral glucose tolerance testing) that will allow us to look at these various predictors and further understand the mechanisms of diabetes following acute pancreatitis.

Is there anything else you'd like to say about this work?

Dr. Hart: The estimates in this study may not be generalizable. As a preliminary analysis, four-year follow-up was available for only approximately 50% of the cohort. Additionally, approximately 40-50% of the study patients had non-mild severity of acute pancreatitis. This distribution of more severe disease may overestimate risks at the population level, so additional population-based studies are awaited to provide complementary results.

Dr. Hart reported having no relevant disclosures.

Summary content

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.

Acute pancreatitis is not 'one-and-done'

"The reality is that while 96–98% of patients survive the acute event, a large proportion face clinically meaningful long-term pancreatic consequences that can be missed once they leave the hospital."

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