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triglycerides by increasing LPL activity. Increased fatty acid
oxidation by stimulating peroxisome proliferator-activated
receptor alpha and enhanced clearance of very Low-density
lipoprotein (LDL) through the reduced action of apolipoprotein C-III are other proposed mechanisms of triglyceride lowering by gemfibrozil.8 Using a combination approach with
insulin, heparin, and gemfibrozil should quickly reduce circulating triglycerides in patients with HTGP. Reducing triglyceride concentrations should result in a reduction in the
duration and severity of the disease.4
Many pharmacological treatment options for HTGP have
been put forth, which include insulin, heparin, and/or fenofibrates as part of the pharmacological treatment; however, the
safety and efficacy for individual treatment options is still
lacking.9 A proposed algorithm for treatment was put forth by
Tsuang and colleagues that includes the use of insulin and
oral antitriglyceride agents as a part of HTGP treatment and
as a suggested means of reducing serum triglyceride concentrations.4 However, currently, no definitive guidelines exist
for the treatment of HTGP.7 Previous studies on the treatment
of HTGP with insulin, heparin, and/or fenofibrates include
only case reports and small case series.3,5,6,9 These reports
show that insulin alone, insulin in combination with heparin,
and insulin in combination with gemfibrozil and niacin are all
possibly effective management options for HTGP. This case
series was performed to describe the effects of insulin, heparin, and gemfibrozil in combination for patients with HTGP.

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transferred from an outside hospital after treatment began
without sufficient records available to track the progress of
that treatment.

Data Collection and Study Outcomes
The primary effectiveness outcome was time to resolution of
HTGP, defined as achievement of a serum triglyceride concentration below 1000 mg/dL. Both 500 and 1000 mg/dL
have been used as target serum triglyceride concentrations
without noticeable differences in complications1,4,9; at our
institution, we use 1000 mg/dL. The primary safety outcome
was development of complications associated with the therapies employed in the management of HTGP. Baseline and
clinical characteristics were determined, including Charlson
comorbidity index score, Ranson criteria score, and laboratory values relevant to the management of HTGP.

Statistical Analysis
The primary outcomes and clinical characteristics were evaluated with counts and percentages. The primary effectiveness outcome could only be evaluated in patients for whom a
serum triglyceride concentration below 1000 mg/dL was
reported. All data were analyzed using Excel 2013 (Microsoft
Corporation, Redmond, Washington).

Results
Methods
Study Design and Setting
The institutional review board at our university approved
this case series. Data were collected from electronic health
records of patients admitted to a single tertiary care hospital
between January 2008 and May 2015. This institution has
332 adult beds, 52 of which are located in an intensive care
unit (ICU). There was no formal protocol for HTGP management in place at the institution during the study period.

Patients
Patients were eligible for inclusion if they were at least 18
years of age, were diagnosed with HTGP, and received the
combination of a continuous infusion of insulin, subcutaneous heparin, and oral gemfibrozil concomitantly for the intention of treating HTGP. These medications are not approved by
the US Food and Drug Administration for this indication.
Patients who were receiving a continuous infusion of insulin
and developed blood glucose values below 200 mg/dL were
provided dextrose infusions to continue infusion therapy.
Patients excluded from this study were those who had a
diagnosis of acute pancreatitis not secondary to hypertriglyceridemia. Also excluded were patients diagnosed with hypertriglyceridemia-induced acute pancreatitis (HTPG) who were

Of the patient charts reviewed, 6 met the criteria for inclusion. The average Ranson criteria score in our cohort was 5
(range: 2-8), and 5 of the 6 patients had a Ranson criteria
score of 3 or greater, indicating severe pancreatitis. The average triglyceride level upon admission was 3501 mg/dL
(range: 1594 to greater than 5000), average amylase was 526
U/L (142 to 1282), and average lipase was 939 U/L (115 to
2730). Other baseline and clinical characteristics are provided in Table 1. All patients received a continuous infusion
of insulin (initiated at 1-2 U/h), subcutaneous heparin, and
oral gemfibrozil for at least 1 day at the start of the treatment
course. Half of the patients also received a statin and 1 patient
received niacin in addition to gemfibrozil (Table 2).
Five patients experienced a resolution of HTGP. Patients
achieved this target on different days: day 3 (n = 3), day 4 (n
= 1), and day 5 (n = 1). One patient's triglyceride levels were
not monitored beyond day 2, and attainment of treatment
success could not be ascertained definitively. One patient
developed an episode of hypoglycemia. No other adverse
drug events were seen (Table 2).

Discussion
Combination therapy with heparin, insulin, and gemfibrozil
is safe and efficacious in lowering the serum triglyceride
concentration in patients experiencing HTGP. Half of the

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