OR12-1 Closed-Loop Glucagon Administration for the Automated Prevention and Treatment of Hypoglycemia in Type 1 Diabetes

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR12-Fresh Thoughts on Diabetes Treatment
Friday, April 1, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 11:45 AM
Room 210 (BCEC)

Clinical Fellows Abstract in Diabetes
Laya Ekhlaspour*1, Courtney Balliro2, Firas H. El-Khatib3, Debbie Mondesir4, Manasi Sinha2, Kendra L Magyar2, Mallory Hillard5, Lisa Dao6 and Steven Jon Russell2
1Massachusett General Hospital, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Boston University, Boston, MA, 4Massachusett General Hospital, Boston, 5Massachusetts General Hospital, 6University of California – Riverside
Introduction: Tight glycemic regulation is important to avoid complication from diabetes, but it is difficult to achieve without hypoglycemia. One approach to this problem has been development of insulin pumps that use information from a continuous glucose monitor (CGM) to stop insulin delivery at a user-defined threshold. Effectiveness is limited by slow absorption of insulin and the continued absorption of already-delivered insulin after the infusion is stopped. An alternative approach is a pump that automatically gives micro-dose glucagon to prevent hypoglycemia.

Material and Methods: We conducted a double-blinded, randomized, placebo controlled crossover study involving 22 adult subjects with type 1 diabetes who used an insulin pump or multiple daily injections, had a self-reported average frequency of hypoglycemia <60 mg/dl of at least twice a week, and reported inconsistent or absent symptoms with blood glucose <50 mg/dl. Participants administered their own insulin as usual while receiving either glucagon or placebo (filled from coded vial blinding devices) for 24 hours at a time from an automated bionic pancreas system. During the 2-week study, days were randomized to glucagon or placebo in blocks of two (7 days of each). The primary outcome was area over the curve <60 mg/dl (AOC<60), a measure of total hypoglycemia exposure, on glucagon vs. placebo days. Secondary outcomes included AOC<60 during the nighttime (11:00 PM – 7:00 AM), time <60 mg/dl, incidents of symptomatic hypoglycemia, mean CGM glucose, mean glucagon dosing on glucagon days, and daily self-reported nausea on a visual analog scale.

Results: The AOC <60 mg/dl was reduced by 75% on glucagon vs. placebo days (851 ± 748 vs. 3,414 ± 2,242 mg/dl·min, p<0.001). There was a 91% reduction in AOC<60 at night on glucagon vs. placebo days (117 ± 204 vs. 1,309 ± 1,476 mg/dl·min, p<0.0001). Subjects spent 74% less time with BG <60 mg/dL on glucagon vs. placebo days (1.2 ± 0.8% versus 4.7 ± 3.6%; p<0.0001). There were half as many symptomatic hypoglycemia episodes on glucagon vs. placebo days (0.6 ± 0.4 versus 1.2 ± 0.8 incidents per day; p<0.0001). Blinding was effective, with subjects correctly guessing their daily assignment to glucagon or placebo in a daily survey on 42% of days (similar to chance). There was no difference in mean CGM glucose on glucagon vs. placebo days (153 ± 28 vs. 152 ± 27 mg/dl, p=0.6). The mean total daily dose of glucagon was 0.48 mg on glucagon days. There was a trend for more self-reported nausea on glucagon vs. placebo days, but this did not reach statistical significance (1.1 ± 0.6 vs. 0.4 ± 0.7 cm on a 10 cm scale, p=0.05). There was no unexpected or severe adverse events on either glucagon or placebo days.

Conclusions: Automated glucagon administration effectively reduced hypoglycemia in patients with type 1 diabetes, and was well tolerated.

Disclosure: SJR: Scientific Board Member, Tandem Diabetes Care, Ad Hoc Consultant, Sanofi, Speaker, Eli Lilly & Company, Principal Investigator, Eli Lilly & Company, Principal Investigator, Tandem Diabetes Care, Speaker, Dexcom, Speaker, Sanofi, Principal Investigator, Dexcom, Scientific Board Member, Companion Medical. Nothing to Disclose: LE, CB, FHE, DM, MS, KLM, MH, LD

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo

Sources of Research Support: American Diabetes Association 7-12-HYPO-07; NIH/NIDDK Training Grant#: 2T32DK007028-41