A single-patient case report published in Cardiovascular Diabetology – Endocrinology Reports describes a woman with type 2 diabetes and recurrent hypertriglyceridemia-mediated acute pancreatitis who, after starting the dual incretin drug tirzepatide, experienced normalized triglycerides, improved glycemic control, discontinuation of all insulin therapy, and twelve months without a further pancreatitis episode. The authors, Benjamin Lechner, Katharina Lechner, Ines Freibothe and Anja Vogt, emphasize that their observation is an association only and cannot establish that tirzepatide prevented recurrence.
Hypertriglyceridemia-mediated acute pancreatitis accounts for roughly one to ten percent of acute pancreatitis cases and typically occurs in the setting of diabetes and broader metabolic dysfunction. Current recommendations discourage incretin-based therapy in patients with a history of pancreatitis, a caution rooted in early concerns about a possible link between GLP-1 receptor agonists and pancreatic inflammation. The authors note that larger contemporary analyses have not shown a consistent increase in pancreatitis risk with GLP-1 receptor agonists or tirzepatide compared with other glucose-lowering agents, yet clinical hesitancy persists. Their report was designed to illustrate how an individualized, monitored approach might be justified in selected patients whose pancreatic injury appears metabolically driven rather than drug-related or hereditary.
The patient, born in 1993, first came to medical attention in 2018 when routine laboratory testing revealed marked hypertriglyceridemia, with triglycerides of 1,300 milligrams per deciliter. At that time her body mass index was 22 kilograms per square meter, well within the normal range, and her only regular medication was an inhaled formoterol and budesonide combination for asthma. Concomitant metabolic testing showed a HbA1c of 5.8 percent, a HOMA-IR of 2.6, and a Matsuda index of 3.7, a pattern indicating liver and whole-body insulin resistance without overt diabetes. Lifestyle modification and fenofibrate were initiated, but triglyceride levels remained highly variable over the following years, fluctuating between 200 and 2,000 milligrams per deciliter. There was no relevant alcohol use, no estrogen therapy, and no other obvious secondary cause of severe hypertriglyceridemia.
In 2022, diabetes mellitus was diagnosed with a HbA1c of 6.8 percent. Diabetes-associated autoantibodies were negative and C-peptide levels were elevated, supporting type 2 diabetes rather than autoimmune diabetes. Metformin was started but later discontinued because of intolerance. From 2023 onward the picture worsened considerably: the patient suffered one episode of acute pancreatitis in 2023 and two further episodes in 2024, each associated with very high triglyceride levels and hospitalization. Because of metformin intolerance and the need for reliable glycemic control, clinicians started an intensified conventional insulin regimen with basal insulin glargine U300 and prandial insulin lispro at 0.3 to 0.4 international units per kilogram per day. Despite continued fenofibrate at 250 milligrams daily and high-dose omega-3 fatty acids at 4 grams per day, triglyceride control remained poor.
The turning point came in early March 2025, when the patient presented with upper abdominal pain. On admission, triglycerides peaked at 4,400 milligrams per deciliter and C-reactive protein reached 28.8 milligrams per deciliter. Acute pancreatitis was confirmed, representing her fourth symptomatic episode. Her BMI at that point was 24 kilograms per square meter and HbA1c was 6.9 percent. Further imaging and clinical assessments supported two additional diagnoses: chronic fibrosing pancreatitis and severe metabolic dysfunction-associated steatotic liver disease, known as MASLD. During hospitalization, triglycerides fell rapidly from 4,400 to 335 milligrams per deciliter under prolonged fasting and intensified intravenous and subcutaneous insulin therapy, while fenofibrate and omega-3 fatty acids were continued. The authors are explicit that this acute improvement occurred before tirzepatide was started and reflects the expected effect of strict caloric restriction and intensive insulin treatment in severe hypertriglyceridemia, not any effect of the new drug.
Before considering tirzepatide, the team conducted a comprehensive genetic work-up addressing two separate questions. Targeted Sanger sequencing after specific PCR amplification of PRSS1, SPINK1, CTRC and the CEL-HYB allele excluded hereditary pancreatitis, revealing no pathogenic variants. A monogenic cause of severe hypertriglyceridemia was evaluated with a next-generation sequencing hyperlipoproteinemia panel, which likewise identified no pathogenic or likely pathogenic variants, and copy number analysis showed no exon-spanning deletions or duplications. The panel did, however, detect a homozygous APOA5 *3 haplotype, p.Ser19Trp, classified as a risk factor rather than a pathogenic variant. This haplotype, with a minor allele frequency of 0.1 to 15 percent depending on ethnicity, has been associated with susceptibility to hypertriglyceridemia and late-onset hyperchylomicronemia and may have contributed to the severe triglyceride phenotype in combination with metabolic risk factors. Physical examination showed preserved subcutaneous adipose tissue without regional lipoatrophy, and the overall phenotype was one of relative sarcopenia with predominant abdominal adiposity rather than a classical lipodystrophic pattern.
Given the recurrent pancreatitis, chronic pancreatic damage with preserved insulin secretion, persistent metabolic dysfunction, and the burden of the intensified insulin regimen, tirzepatide was started on March 27, 2025 at 5 milligrams once weekly. At initiation, triglycerides were 335 milligrams per deciliter, HbA1c was 7.0 percent, C-reactive protein was 0.9 milligrams per deciliter, ALT was 32 units per liter, and GGT was 55 units per liter. Over the following three months, both prandial insulin lispro and basal insulin glargine U300 were gradually tapered and fully discontinued by June 18, 2025, without deterioration in glycemic control. By that date triglycerides had fallen to 137 milligrams per deciliter, HbA1c to 6.3 percent, and C-reactive protein to 0.7 milligrams per deciliter, allowing fenofibrate and omega-3 fatty acids to be stopped the same day. The metabolic gains therefore persisted even after withdrawal of the two triglyceride-lowering co-medications.
Follow-up continued through one year. After six months of tirzepatide, in September 2025, the patient had lost approximately 10 kilograms, bringing BMI to 20 kilograms per square meter, with triglycerides of 177 milligrams per deciliter, HbA1c of 5.8 percent, C-reactive protein of 0.6 milligrams per deciliter, ALT of 39 units per liter and GGT of 42 units per liter. Liver enzymes rose mildly and transiently at three months, with ALT of 85 and GGT of 79 units per liter, before normalizing by twelve months to ALT of 26 and GGT of 31 units per liter. By February 2026, weight had stabilized with no further loss, fasting triglycerides were 85 milligrams per deciliter, HbA1c had improved to 5.5 percent, and C-reactive protein had normalized to 0.4 milligrams per deciliter. Rosuvastatin at 5 milligrams daily was started before the final assessment because carotid atherosclerotic plaques were detected. No further pancreatitis episodes occurred during the twelve months of follow-up, and the patient reported a marked improvement in quality of life.
The authors interpret the chronological sequence as supporting a beneficial association between tirzepatide and subsequent metabolic stabilization in a patient without obesity, while stressing the limits of that inference. A single case cannot establish whether tirzepatide prevented recurrence of hypertriglyceridemia-mediated pancreatitis, and the favorable course may reflect other factors. They also acknowledge that formal body-composition assessments, including DEXA, skinfold measurements and serum leptin levels, were not performed, so a partial lipodystrophy syndrome cannot be definitively excluded despite the absence of overt regional lipoatrophy and the negative genetic testing. On the supportive side, they cite randomized trials and meta-analyses that have not shown a consistent pancreatitis signal for GLP-1 receptor agonists or tirzepatide, evidence that tirzepatide improves glycemia, body weight and triglycerides in type 2 diabetes independent of body weight, and recent data suggesting a decreased risk of acute pancreatitis in people with type 2 diabetes and a history of acute pancreatitis treated with tirzepatide or semaglutide. Because weight stabilized after six months, the team considered continued tirzepatide at 5 milligrams justified under regular weight monitoring, with plans for cautious dose reduction to 2.5 milligrams or supervised discontinuation if further weight loss occurred, alongside dietary counseling to ensure adequate protein and micronutrient intake and recommended resistance exercise.
The broader message of the report is deliberately cautious. The authors argue that metabolic pancreatitis related to diabetes and obesity may be underrecognized, and that concerns partly driven by confounding by indication should not automatically preclude carefully monitored incretin-based therapy when metabolic dysfunction appears to be the dominant contributor to pancreatic injury. Their conclusion frames the case as supporting careful, individualized consideration of incretin therapy in metabolically driven pancreatitis rather than automatic exclusion based solely on prior pancreatitis history. For clinicians, the practical takeaway is not that tirzepatide treats pancreatitis, a claim the data cannot support, but that the absolute contraindication implied by older fears may deserve re-examination in selected, closely monitored patients. Confirmation will require controlled studies; what this report supplies is a detailed, genetically characterized case demonstrating that such an approach is feasible and, in this one patient, was followed by a striking and sustained metabolic recovery.
Subject of Research: A case report of tirzepatide treatment in a patient with type 2 diabetes and recurrent hypertriglyceridemia-mediated pancreatitis
Article Title: Tirzepatide in recurrent hypertriglyceridemia-mediated pancreatitis and type 2 diabetes: a case report
Article References: Lechner, B., Lechner, K., Freibothe, I., & Vogt, A. (2026). Tirzepatide in recurrent hypertriglyceridemia-mediated pancreatitis and type 2 diabetes: a case report. Cardiovascular Diabetology – Endocrinology Reports, 12(1), Article 50. https://doi.org/10.1186/s40842-026-00318-z
Image Credits: AI Generated
DOI: 10.1186/s40842-026-00318-z
Keywords: tirzepatide, hypertriglyceridemia, pancreatitis, type 2 diabetes, incretin therapy, triglycerides, case report, insulin resistance, MASLD, APOA5, GLP-1 receptor agonists, metabolic dysfunction
News Source: Ophelia Keating. (October 29, 2026). Tirzepatide Tied to Pancreatitis-Free Year in Severe Diabetes Case. Scienmag.
