Background Insulin is a widely accepted treatment for hypertriglyceridemia-associated acute pancreatitis (HTG-AP), whereas heparin is of uncertain benefit, so we compared low-molecular-weight heparin (LMWH) with insulin versus insulin alone in HTG-AP patients.

Methods This multi-center randomized trial enrolled patients admitted within 48 hours of HTG-AP onset to receive either 4000 IU LMWH 12 hourly for three days with insulin (LMWH + insulin group) or insulin alone (insulin group). The primary composite endpoint was the incidence of new-onset organ failure and/or mortality.

Results Over 43 months, 533 patients were assigned to either LMWH + insulin (n = 264) or insulin (n = 269). The primary endpoint occurred in 66 (25%) patients in the LMWH + insulin group and 76 (28.3%) in the insulin group (relative risk [RR] 0.89, 95% confidence interval [CI] 0.67-1.17; p = 0.40). There were no significant differences in safety outcomes between the two groups, although TG rebound was more frequent in the insulin group (RR 0.53, 95% CI 0.28-1.01; p = 0.05). Subgroup analysis of patients with baseline TG levels ≥ 22.6 mmol/L (n = 188) showed a lower incidence of new-onset persistent SIRS (1% VS 13%, p = 0.003) and new-onset respiratory failure (22% VS 36%, p = 0.04) in the LMWH + insulin group compared to the insulin group.

Conclusions LMWH with insulin was not superior to insulin alone in HTG-AP, although LMWH may improve outcomes in patients with very high TG levels.