Original Investigation 

Gastroenterology and Hepatology

Low-Molecular-Weight Heparin Plus Insulin in Hypertriglyceridemic Acute Pancreatitis: A Randomized Clinical Trial

Wenhua He, Ling Ding, Zhijun Liu, et al

JAMA Netw Open 2025;8;(11):e2542124. doi:10.1001/jamanetworkopen.2025.42124

Key Points

Question  Is low-molecular-weight heparin combined with insulin superior to insulin alone in improving clinical outcomes in hypertriglyceridemic pancreatitis?

Findings  In this multicenter randomized clinical trial of 533 adults with acute pancreatitis, low-molecular-weight heparin with insulin was not superior to insulin alone in reducing new-onset organ failure and/or mortality.

Meaning  Low-molecular-weight heparin might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis.

Abstract

Importance  Although insulin is widely used for early lipid lowering in hypertriglyceridemic acute pancreatitis, the clinical benefit of heparin combined with insulin remains unclear.

Objective  To examine whether low-molecular-weight heparin (LMWH) combined with insulin is superior to insulin alone in improving clinical outcomes in hypertriglyceridemic acute pancreatitis.

Design, Setting, and Participants  This multicenter, open-label, parallel-group, superiority randomized clinical trial was conducted from September 21, 2019, to April 2, 2023, across 13 tertiary hospitals in China. The duration of follow-up was 30 days after randomization. Patients aged 18 to 85 years were eligible if they met the diagnostic criteria for acute pancreatitis, presented with baseline serum triglyceride levels between 1000 and 3550 mg/dL, and were admitted within 48 hours of symptom onset.

Interventions  Participants received either subcutaneous LMWH (4000 IU every 12 hours for 3 days) plus insulin (LMWH plus insulin group) or insulin alone (insulin group).

Main Outcomes and Measures  The primary end point was a composite of new-onset organ failure (defined as organ failure occurring after randomization but absent during the 24-hour prerandomization period) and/or all-cause mortality within 30 days after randomization.

Results  Among 533 randomized patients (median [IQR] age, 39 [33-46] years; 406 [76.2%] male), 264 were randomized to LMWH plus insulin and 269 to insulin alone. The primary end point occurred in 66 (25.0%) of the LMWH and insulin group vs 76 (28.3%) of the insulin group (relative risk [RR], 0.89; 95% CI, 0.67-1.17; P = .40). Both groups achieved the triglyceride target (<500 mg/dL) in a median (IQR) of 2 (1-3) days (P = .94). Safety outcomes were similar between groups, including new-onset bleeding events (RR, 0.61; 95% CI, 0.15-2.53; P = .73), triglyceride rebound (RR, 0.53; 95% CI, 0.28-1.01; P = .05), and drug-related adverse events (RR, 0.79; 95% CI, 0.30-2.10; P = .64).

Conclusions and Relevance  In this randomized clinical trial, the combination of LMWH and insulin failed to demonstrate superior efficacy vs insulin alone in patients with hypertriglyceridemic acute pancreatitis. LMWH might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis.

Trial Registration  ChiCTR.org.cn Identifier: ChiCTR1900023640