What is the role of insulin infusion in hypertriglyceridemia-induced acute pancreatitis?

Acute pancreatitis is the most common cause of hospitalization for gastrointestinal disease and accounts for more than 275,000 hospital admissions in the US each year.1 Although alcohol use and gallstones are the most common causes of acute pancreatitis, hypertriglyceridemia plays a role in about 10% of cases.2 Generally, hypertriglyceridemia is considered the primary etiology for pancreatitis when gallstones are not present, there is no significant history of alcohol use, and the triglyceride level exceeds 1,000 mg/dL.3 Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) presents similar to other cases of acute pancreatitis, but patients with hypertriglyceridemia are more likely to have a complicated course and a greater risk of organ failure.4

Acute pancreatitis treatment
The basic management strategies for acute pancreatitis include intravenous (IV) hydration and pain control.3 The American College of Gastroenterology suggests moderately aggressive fluid resuscitation with lactated Ringer solution. A multimodal approach to pain management is generally recommended with nonsteroidal anti-inflammatory agents for mild pain and the addition of opioids as necessary.5,6 Prophylactic antibiotics are no longer recommended for all patients with acute pancreatitis with their use reserved for infected necrosis.3 Other treatments are patient-specific and often based on the etiology of the pancreatitis.

For patients with HTG-AP, pain management and hydration remain important pieces of the treatment protocol, but management of metabolic abnormalities and prohibiting or limiting food intake are important measures. Fasting alone without other intervention can decrease plasma triglycerides by about 50% in 24 hours.7 However, for patients with risk factors for worse outcomes or more severe disease, additional triglyceride-lowering measures may be considered.8 Features that may indicate the need for more aggressive treatment include: hypocalcemia, lactic acidosis, signs of organ dysfunction or multi-organ failure, or signs of worsening systemic inflammation (≥2 of the following: temperature $>$38.5°C or $<$35.0°C, heart rate $>$90 beats/min, respiratory rate $>$20 breaths/min or PaCo2 of $<$32 mmHg, or white blood cell count $>$12,000 cells/mL, $<$4000 cells/mL, or $>$10% immature forms).

Treatment options for patients with HTG-AP at high-risk for complications or extremely elevated triglyceride levels include insulin infusion, plasmapheresis/plasma exchange, and/or heparin/low-molecular-weight heparin.8,9 Although these agents are known to be effective for lowering triglyceride levels, their utility in HTG-AP is not well established and guidelines for lipid management in patients with endocrine disorders from the Endocrine Society published in 2020 are vague.10 The guidelines recommend against routine use of either insulin infusion or plasmapheresis in patients with HTG-AP and suggest use of plasmapheresis only in patients with extremely elevated triglyceride levels (eg, >10,000 mg/dL) or those at high-risk of complications (eg, pregnancy). The guidelines do not mention the use of heparin products. Thus, the role of pharmacotherapy is unclear.

Evidence for insulin infusion in HTG-AP

Insulin activates lipoprotein lipase and lowers triglyceride concentrations by promoting triglyceride clearance.9 Its efficacy for acutely lowering triglycerides has been documented in patients requiring insulin treatment for hyperglycemia. However, when used alongside glucose, it has also been shown to lower triglycerides in patients with acute pancreatitis who are not hyperglycemic.

Although there are numerous studies evaluating the role of insulin in patients with HTG-AP, the studies are primarily small and observational. Few randomized trials exist, and those trials are limited to comparisons of insulin infusion and plasmapheresis or similar procedure.11,12 It is difficult to draw conclusions from these trials, as plasmapheresis is not an established standard of care, the patient populations are heterogeneous, and the trials are small.

A 2023 review by Gubensek et al, noted the shortcomings of the literature including the lack of systematic reporting of the insulin dose and lack of comparison to fasting alone.13 Only one nonrandomized study compared insulin to fasting alone, and this study did not find insulin to more rapidly lower triglycerides compared with fasting alone.14 Gubensek did note that observational data up to this time found insulin infusions to reduce triglycerides by 40% to 68% in the first 24 hours of administration.

A selection of recent literature after the 2023 review was identified for further analysis and is summarized in the Table. Other observational studies have been published in abstract form and generally support the efficacy of insulin for lowering triglycerides in HTG-AP, but publications lack detail for Table inclusion.15,16

Table. Recent literature evaluating insulin infusions for hypertriglyceridemia-induced acute pancreatitis.17-22
Study designSubjectsInterventionsResultsConclusions
Le 202517Prospective cohortN=54 adults with HTG-AP and TG ≥1000 mg/dLInsulin infusion (0.1 to 0.3 units/kg/hour titrated at caregiver discretion) with dextrose infusion to maintain blood glucose 150 to 200 mg/dLBy 72 hours, 92.6% of patients achieved target TG level (<500 mg/dL).

More rapid TG lowering within the first 12 hours was associated with a lower risk of requiring plasma exchange due to worsening pancreatitis.		Insulin infusion lowers TG levels, with greater TG lowering in the first 12 hours associated with lower risk of worsening pancreatitis.
Tan 202518Retrospective cohortN=171 adults with HTG-AP were included in either the very severe group (TG >2000 mg/dL; n=100) or the severe group (TG >1000 to 2000 mg/dL; n=71)Insulin infusion (0.1 to 0.3 units/kg/hour) with dextrose infusion as needed and LMWH or UFH (n=66 in the very severe group and n=47 in the severe group)

Plasma exchange (n=34 in the very severe group)

NPO (n=14 in the severe group)		Very severe
Clinical outcomes were similar between the insulin group and the plasma exchange groups; however, cost was significantly improved with insulin treatment.

Severe
Clinical outcomes were similar between the insulin group and the NPO groups; however, cost was significantly improved with NPO.		In patients with very severe HTG-AP, insulin may be similarly effective to plasma exchange.

In patients with severe HTG-AP, NPO may be similarly effective to insulin.
Thanh 202519SC, retrospectiveN=89 patients with HTG-AP and TG >1000 mg/dLInsulin infusion (0.1 to 0.3 units/kg/hour) with dextrose infusion as needed (n=56)

Plasma exchange (n=33)		Median percent TG reduction at 24 hours was greater with plasma exchange (18.2% vs 15.4%); however, the groups were similar at 48 hours (83.6% and 81.9%).

Median LOS was significantly shorter in the insulin group (6 days vs 10 days).		Plasma exchange lowered TG levels faster than insulin. Although insulin-treated patients had shorter LOS, this is likely confounded by the fact that these patients were less ill at baseline than those who received plasmapheresis.
Yacine 202520MC, retrospective, US-based cohort studyN=466 adults with HTG-AP and TG >1000 mg/dLFixed-dose insulin infusion of 0.1 units/kg/hour (capped at 12 units/hour for those weighing ≥115 kg) with dextrose infusion to maintain normoglycemia (n=244)

Standard of care prior to implementation of fixed-dose insulin (could include insulin treatment but not in the protocolized manner) (n=242)		ICU LOS was not different between groups (2.42 days pre-protocol vs 2.82 days post-protocol).

Time to TG <1000 mg/dL was similar between groups (1.55 days pre-protocol vs 1.5 days post-protocol).

Incidence of severe hypoglycemia was similar between groups (1.2% vs 3.6%), but mild hypoglycemia was greater in the post-protocol group (36.6% vs 25.2%).		Fixed-dose insulin offers a standardized approach to HTG-AP and provides outcomes similar to standard care.
Ibarra 2023212-center, retrospective, US-based cohort studyN=40 adults with HTG-AP and a TG ≥1000 mg/dLFixed-dose insulin infusion of 0.1 units/kg/hour for patients with diabetes and 0.05 units/kg/hour for patients without diabetes (both capped at 10 units/hour) with dextrose infusion to maintain normoglycemia (n=20)

Usual care prior to implementation of fixed-dose insulin (n=20)		More patients achieved TG levels <500 mg/dL in the fixed-dose insulin group (85% vs 50%) with similar incidence of hypoglycemia (5% in the post-implementation group vs 15% pre-implementation).More patients achieved TG goals with fixed-dose insulin protocol compared with standard care without increasing hypoglycemia.
Perez 2023222-center, retrospective, US-based cohort studyN=67 adults with HTG-AP and a TG >1000 mg/dLFixed-dose insulin infusion of 0.1 units/kg/hour (capped at 15 units/hour) with dextrose infusion to maintain normoglycemia (n=41)

Usual care prior to implementation of fixed-dose insulin (n=26)		All patients achieved a TG level ≤1000 mg/dL. Patients treated with the fixed-dose insulin infusion reached TG ≤1000 mg/dL in 26.9 hours compared with 43.3 hours (p=0.07) in the control group.

There was no difference between groups in achieving a TG level ≤500 mg/dL (76.9% with control and 75.6% with insulin protocol), but those treated with the treated with fixed-dose insulin achieved the goal significantly faster (49.2 hours versus 70.9 hours; p=0.04).

Hypoglycemia was numerically lower in the insulin infusion protocol group despite higher insulin infusion rates (7.3% vs 19.2%).		The use of an insulin infusion protocol, compared with usual care, resulted in quicker achievement of a TG level ≤500 mg/dL and a trend toward faster achievement of TG ≤1000 mg/dL without an increased risk of hypoglycemia.
Abbreviations: HTG-AP=hypertriglyceridemia-induced acute pancreatitis; ICU=intensive care unit; LMWH=low-molecular-weight heparin; LOS=length of stay; MC=multicenter; NPO=nothing by mouth; SC=single-center; TG=triglyceride; UFH=unfractionated heparin.

Discussion
Current evidence for insulin infusion in the treatment of HTG-AP is limited, primarily derived from small, nonrandomized, observational studies.17-22 Recent literature offers improved dosing guidance compared with older literature, and most studies initiate insulin infusion at 0.1 units/kg/hour. Both fixed-dose and titratable regimens have been studied, with increasing evidence supporting a fixed-dose protocol. The maximum dose has reached as high as 15 units/hour, but there is little information available to support an appropriate upper limit.22 Notably, some studies have used doses as low as 0.05 units/kg/hour in patients without hyperglycemia, but there is less evidence for doses under 0.1 units/kg/hour.21 Generally, 5% or 10% dextrose infusions are used to maintain normoglycemia and frequent monitoring of blood glucose and electrolytes is required.

Despite the multitude of observational studies, the lack of high-quality literature for insulin use in HTG-AP leaves many questions unanswered.17-22 A primary concern is determining who should be treated. Identifying patients with HTG-AP who will benefit from interventions beyond fasting is not well-established, and it is unclear who should receive additional therapy with insulin or plasmapheresis. Most observational studies included patients with established HTG-AP and triglyceride levels exceeding 1,000 mg/dL, but baseline characteristics were heterogenous and inconsistently reported. Evidence for therapeutic outcomes is also lacking. Triglyceride lowering is an established outcome; however, there is little information on length of stay, morbidity, or mortality. Some observational studies also combined heparin or low-molecular-weight heparin with the insulin infusion, but a recent randomized trial failed to show additional benefit with the addition of low-molecular-weight-heparin compared to insulin alone.23

Conclusion
Insulin infusions are commonly used in patients with HTG-AP to promote rapid triglyceride lowering and reduce serious disease or related complications. However, it is unclear which patients benefit from insulin infusions and its place in therapy is not well-established.

References

  1. Wang CF, Tariq A, Chandra S. Acute pancreatitis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 2, 2025.
  2. Oppenlander KE, Chadwick C, Carman K. Acute pancreatitis: Rapid evidence review. Am Fam Physician. 2022;106(1):44-50.
  3. Tenner S, Vege SS, Sheth SG, et al. American College of Gastroenterology Guidelines: Management of acute pancreatitis. Am J Gastroenterol. 2024;119(3):419-437. doi:10.14309/ajg.0000000000002645
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  5. van den Berg FF, Boermeester MA. Update on the management of acute pancreatitis. Curr Opin Crit Care. 2023;29(2):145-151. doi:10.1097/MCC.0000000000001017
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  10. Newman CB, Blaha MJ, Boord JB, et al. Lipid management in patients with endocrine disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2020;105(12):dgaa674. doi:10.1210/clinem/dgaa674
  11. Gubensek J, Andonova M, Jerman A, et al. Comparable triglyceride reduction with plasma exchange and insulin in acute pancreatitis – a randomized trial. Front Med (Lausanne). 2022;9:870067. doi:10.3389/fmed.2022.870067
  12. He WH, Yu M, Zhu Y, et al. Emergent triglyceride-lowering therapy with early high-volume hemofiltration against low-molecular-weight heparin combined with insulin in hypertriglyceridemic pancreatitis: A prospective randomized controlled trial. J Clin Gastroenterol. 2016;50(9):772-778. doi:10.1097/MCG.000000000000055
  13. Gubensek J. The role of apheresis and insulin therapy in hypertriglyceridemic acute pancreatitis-a concise review. BMC Gastroenterol. 2023;23(1):341. doi:10.1186/s12876-023-02957-3
  14. Dhindsa S, Sharma A, Al-Khazaali A, et al. Intravenous insulin versus conservative management in hypertriglyceridemia-associated acute pancreatitis. J Endocr Soc. 2019;4(1):bvz019. doi:10.1210/jendso/bvz019
  15. Rangel ML, Popa A, Hejal R. Evaluation of high-dose insulin for the treatment of hypertriglyceridemic pancreatitis. Crit Care Med. 2023:51(1):93. doi: 10.1097/01.ccm.0000906612.50716.76
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  23. He W, Ding L, Liu Z, et al. Low-molecular-weight heparin plus insulin in hypertriglyceridemic acute pancreatitis: A randomized clinical trial. JAMA Netw Open. 2025;8(11):e2542124. doi:10.1001/jamanetworkopen.2025.42124

January 2026

Prepared by:
Courtney Krueger, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

The information presented is current as of December 10, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.