Pancrelipase Improves Nutrient Absorption in Patients with Exocrine Pancreatic Insufficiency Who Are Also Diabetic

A new analysis of trial data shows that patients with exocrine pancreatic insufficiency benefit about as much from pancrelipase delayed-release capsules (Creon) whether or not they have diabetes mellitus.

A new analysis of trial data shows that patients with exocrine pancreatic insufficiency benefit about as much from pancrelipase delayed-release capsules (Creon) whether or not they have diabetes mellitus.

Researchers pulled data on 36 diabetics and 18 comparable people with no diabetes who participated in a randomized, placebo-controlled trial of pancrelipase in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or either total or partial pancreatectomy.

All patients began with 5 days of placebo and were then randomized between another week of placebo or a week of pancrelipase (72,000 lipase units per meal and 36,000 lipase units per snack). Trial investigators measured each patient’s coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CAN) at the end of the study period.

The subsequent analysis found that pancrelipase use was associated with higher figures than placebo use in both diabetic patients (CFA, 36.0% vs 7.5%; P < 0.0001; CNA, 33.4% vs 3.7%; P = 0.0002) and non-diabetic patients (CFA, 25.2% vs 12.3%; P = 0.0326; CNA, 39.1% vs 17.6%; P = 0.1187). The different outcomes for diabetic and non-diabetic patients were not significant, either in the case of CFA (P = 0.0802) or CNA (P = 0.2934). Incidents of adverse events such as hyperglycemia and hypoglycemia were similar in the pancrelipase and placebo arms of the trial.

“Pancrelipase improved fat and protein absorption in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy, with or without diabetes mellitus, and matched the safety profile previously reported,” the authors of the analysis wrote in Pancreas.

The underlying trial did not last long enough to determine whether the use of pancrelipase led to weight gain among diabetic patients, but at least 1 previous study has demonstrated significant weight gain in other patients with exocrine pancreatic insufficiency.

That trial, an open label expansion of a 7-day double-blinded trial, lasted a full 6 months. The 48 patients who completed the trial took an average of 186,960 units of lipase per day (standard deviation ± 74,640) and achieved a mean body weigh increase of 2.7 kg (±3.4 kg; p<0.0001). They also experienced a mean reduction in daily stool frequency of 1 (±1.3; p<0.001).

Investigators also noted that the percentage of subjects with normal stools increased from 21.6% at baseline to 68.1% at study end. Improvement in stool consistency occurred in 26 of 47 subjects (55.3%); only 2 of 47 subjects (4.3%) reported worsening of stool consistency. The percentage of subjects with no flatulence increased from 15.7% at baseline to 44.7% at study end. Some 23 of 47 subjects (48.9%) reported reductions in flatulence, whereas 6 of 47 subjects (12.8%) reported worsening of flatulence.

Only 4 patients (7.8%) suffered adverse events that investigators considered possibly or probably related to treatment. They were diarrhea, abdominal distension, abdominal pain, flatulence and weight increase and each occurred in 1 subject. (The weight increase was considered an adverse event because it occurred in a very rare patient, who was obese at baseline.)

“Although patients in this study had been managed previously with standard PERT (pancreatic enzyme replacement therapy), the significant weight gain, particularly in the patients with body mass index <18.5 kg/m2 at baseline, suggests that pancrelipase treatment, in conjunction with other factors, improved the nutritional status of these patients,” the study authors wrote. “These other factors may have included improved adequacy of PERT dosing, improved nutritional intake and the quality of care received during the study period.”