WS16.06Amylase as a potential non-insulin adjunct to manage CF-related blood glucose levels

Background

People with CF have a later peak in blood glucose after a meal than is seen in health; this delay is greater in those with impaired glucose tolerance. We hypothesized that an efficacious amylase could lead to improved post-prandial glucose patterns. ANG003 is a microbially-derived lipase, protease and amylase product. Its amylase is pH stable, can interact with substrate in the fed stomach and does not need enteric coating. A clinical study used continuous glucose monitoring (CGM) and C-peptide response to a test meal to investigate the impact of ANG003 on starch digestion and absorption.

Methods

This multicenter study evaluated the effect of a single dose of orally administered ANG003 in adults with CF. Subjects were randomized to either 40, 80 or 120 mg amylase given with microbial lipase and protease and a high-fat breakfast containing ∼100 gm total carbohydrates, including 20 gm of potato starch. A blinded Dexcom G6Pro CGM was placed 24 hours before each study and continued for 4 hours after the meal. Each subject was studied once without and once with the specified amylase dose. C-peptide levels were drawn prior to and 1, 2, 4 and 6 hours after each test meal.

Results

Fifty-one subjects were enrolled. Subjects without diabetes (n=32) had baseline glucose=110 mg/dL. Compared to no amylase, all doses shifted glucose curves to the left; a significant difference was seen with the 120 mg dose (p=0.04). No difference in C-peptide levels were observed compared to no enzyme. Fewer CGM readings below 70-80 mg/dL and fewer readings above 180-240 mg/dL were noted with ANG003 compared to no enzyme. No differences in glucose or C-peptide were noted in those subjects with diabetes (n=19); they had significant glycemic variability.

Conclusion

We saw an earlier and more physiologic shift of glucose absorption and fewer high and low glucose excursions not accompanied by increased insulin secretion. Amylase may play a supportive role in glucose homeostasis in CF.