The bionic pancreas (BP) continues to make all insulin dosing decisions autonomously when continuous glucose monitoring (CGM) data is not available. Basal insulin is given based on a profile ...determined autonomously by the BP when CGM data was available. Meals are announced as Breakfast, Lunch, or Dinner and by relative size (Usual, Less, More) ; insulin dosing is based on adaptation that occurred when CGM data was available. Insulin may be delivered, or temporarily suspended, autonomously by the BP in response to entered blood glucose (BG) values. At the end of the 13-week Pivotal RCT of the BP in type 1 diabetes, participants in the BP group could participate in a study testing the BP without CGM input. Unblinded CGM was replaced by blinded CGM not connected to the BP for ∼49.5 hours. Participants were to enter fingerstick BG values every ∼2 hours during the day and once overnight. Adherence with BG entry requirements by the 54 participants (aged 7-70) was high. There was no severe hypoglycemia or DKA. The frequency of CGM-measured hypoglycemia was similar during the BG Period to the RCT and Pre-Randomization periods. Hyperglycemia metrics were nominally higher during the BG Period than the RCT, but nominally lower than the Pre-randomization Baseline period. The BP can autonomously determine all insulin doses and achieve safe glucose control without CGM input when intermittent BG values are provided by the user.
Disclosure
C. A. Balliro: Consultant; Beta Bionics, Inc., Zealand Pharma A/S.
Funding
Funding from National Institute of Diabetes and Digestive and Kidney Diseases (#1UC4DK108612-01) . Funding and bionic pancreas devices from Beta Bionics, Inc. Fast-acting insulin aspart and insulin aspart provided by Novo Nordisk Insulin lispro by Eli LillyBlood glucose meters and test strips (Contour Next One Blood Glucose Monitoring System) provided by Ascensia Diabetes Care, Basel, CH. Continuous glucose monitor sensors and transmitters were purchased from Dexcom, Inc. at a discounted price.
Background: The Medtronic MiniMed™ AHCL system that autocorrects to 120mg/dL every five minutes and has an automated basal target of 100mg/dL or 120mg/dL has demonstrated improved A1C and time in ...range1,2 or improved time in closed-loop control,3 compared to open-loop run-in or control. Glycemic outcomes of study participants who used a different baseline therapy (HCL, SAP or CSII) during the MiniMed™ AHCL pivotal trial were analyzed. Methods: Across 16 sites, participants (N=157, 14-75 years) with T1D underwent a baseline run-in period (~2 weeks) of HCL, SAP or CSII followed by a 90-day study phase with AHCL automated basal and auto-correction. An exploratory analysis compared the mean sensor glucose and percentage of time spent across glucose ranges during the baseline run-in and AHCL-study phase for each cohort. Results: Glycemic outcomes for the overall group and each cohort are shown in the table. Significant changes were observed from run-in to study period for the overall group. The glycemic outcomes that were achieved were similar regardless of the baseline therapy. Conclusion: These MiniMed™ AHCL pivotal trial data demonstrate that the system achieves robust glycemic improvement regardless of baseline therapy.
Objective: We evaluated glycemic outcomes at two glucose targets with each of two configurations (bihormonal and insulin-only) of the bionic pancreas (BP) in the setting of standardized exercise in ...adults with type 1 diabetes.
Methods: 20 participants completed a double-blinded, placebo-controlled (glucagon vs. placebo) , random-order, cross-over trial comparing the bihormonal (BH) and insulin-only (IO) configurations of the BP, each using two glucose targets (1 and 130 mg/dl) ; each arm lasted three days. On the last morning of each arm, fasted subjects exercised on a stationary bike with a heart rate of 120-140 bpm for ∼30 minutes. The primary outcome was number of subjects discordant between the BH and IO arms using the same glucose target for events with plasma glucose (PG) <60 mg/dl for more than minutes (McNemar's Test) . Secondary endpoints included the area over the glucose curve and <60 mg/dl and grams of carbohydrates given for hypoglycemic events (Wilcoxon Signed Rank Test) .
Results: When using the 130 mg/dl glucose target, there were no events with PG<60 mg/dl in either the BH or IO configurations; AOC <60 mg/dl was 0 min*mg/dl for both configurations and no carbohydrates were given. When using the 1mg/dl glucose target, three subjects in the IO arm had an event with a PG <60 mg/dl for more than minutes; no subjects had an event using the BH configuration (p=0.25) . Median AOC <60 mg/dl was 0 0-0 min*mg/dl for both configurations (p=0.18) , and the median amount of carbohydrates required to recover from hypoglycemic events was 0 0-0 grams for both configurations (p=0.56) .
Conclusions: Both configurations of the BP provided safe glycemic regulation using both glucose targets during exercise use. Larger studies will be needed to quantify differences in exercise outcomes between the IO and BH configurations of the BP.
Disclosure
L.E.Castellanos: None. C.A.Balliro: Consultant; Beta Bionics, Inc., Zealand Pharma A/S. J.Sherwood: None. M.Hillard: None. R.Selagamsetty: Employee; Beta Bionics, Inc. H.Zheng: None. F.El-khatib: Employee; Beta Bionics, Inc., Stock/Shareholder; Beta Bionics, Inc. E.Damiano: Other Relationship; Beta Bionics, Inc. S.J.Russell: Advisory Panel; ConvaTec Inc., Eli Lilly and Company, Consultant; Beta Bionics, Inc., Other Relationship; Beta Bionics, Inc., Research Support; Beta Bionics, Inc., Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Companion Medical.
Funding
NIDDK (T32DK007028)
Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin ...delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial.
Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC). No restrictions were placed on diet or activity. The primary outcome was the percent time sensor-measured glucose was in target range 70-180 mg/dL (time in range TIR) on days 3-14 of each arm, and key secondary outcomes included mean continuous glucose monitoring (CGM) glucose and the percent time sensor-measured glucose was in hypoglycemic range <54 mg/dL.
TIR was significantly higher in the BP arm than the UC arm (75 ± 11% vs. 62 ± 22%, P = 0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150 ± 19 vs. 171 ± 45 mg/dL, P = 0.007). There was no significant difference in percent time with sensor-measured glucose <54 mg/dL (0.27% vs. 0.36%, P = 1.0), although self-reported symptomatic hypoglycemia episodes were higher during the BP arm than the UC arm (0.7 vs. 0.4 median episodes per day, P = 0.01). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either arm.
Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting that this may be an important therapeutic option for this patient population.
We performed a non-blinded, random-order, cross-over study in 20 volunteers with type 1 diabetes comparing glycemic regulation by the bihormonal bionic pancreas (BHBP) at three glucose targets (130, ...115, and 100 mg/dl). Subjects went about their daily routines during each 3-day test period. In the BHBP arms, lower glucose targets (130 to 115 to 100 mg/dl) were associated with correspondingly lower mean CGM glucose levels (156±12 to 146±14 to 135±14 mg/dl, p<0.005 for each comparison). There was no corresponding difference in percent time <60 mg/dl (0.6±1.0 % to 0.9±1.2% to 0.8±1.1%, p≥0.22 for each comparison). However, there was a corresponding significant increase in glucagon total daily dose (2.2±1.2 to 5.3±2.3 to 8.3±3.0 µg/kg/day, p≤0.001 for each comparison). Mean daily nausea scores reported on a 10 cm visual analog scale were low and not significantly different between BHBP arms (0.5, 0.8 and 1.1 cm for the 130, 115, and 100 mg/dl glucose targets, respectively, p>0.05 for each comparison). There were no significant differences between the different BHBP arms in average hypoglycemia symptoms per day, average hypoglycemia interventions per day, or average grams of oral carbohydrates taken by subjects to prevent or treat hypoglycemia. The 100 mg/dl glucose target had a higher satisfaction score when compared to the 115 and 130 mg/dl glucose targets (4.3 versus 4.15 and 4.18, respectively; p<0.005 for both comparisons). There was no significant difference in satisfaction score between the 115 and 130 mg/dl glucose targets. The results of the present study show that for the BHBP, the lowest glucose target in this comparison was associated with better glycemic control, no statistically significant increase in side effects, and greater user satisfaction than higher glucose targets.
Disclosure
M. Tuffaha: None. C.A. Balliro: None. M. Hillard: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.
Funding
The Leona M. and Harry B. Helmsley Charitable Trust
Objective: We evaluated the glycemic outcomes with 2 glucose targets in both configurations (bihormonal and insulin-only) of the bionic pancreas (BP) in a home-use study of adults with type 1 ...diabetes.
Research Design and Methods: 20 participants completed a double-blinded, placebo-controlled (glucagon vs. placebo), random-order, four-arm cross-over trial comparing the bihormonal (BH) and insulin-only (IO) configurations of the BP, each using 2 glucose targets (110 and 130 mg/dl); each arm lasted 3 days. Co-primary outcomes were continuous glucose monitor (CGM) mean glucose level and time <54 mg/dl.
Results: For the BH vs. IO configurations using the 130 mg/dl glucose target, the mean CGM glucose was 156±12 vs. 161±17 mg/dl (p=0.11) and the median percentage of time with CGM glucose <54 mg/dl was 0.0% IQR 0-0.52% vs. 0.0% 0-0.35% (p=0.45). For the BH vs. IO configurations using the 110 mg/dl glucose target, the mean CGM glucose was 148±17 vs. 153±15 mg/dl (p=0.21) and the median percentage of time with CGM glucose <54 mg/dl was 0.0% 0-0% vs. 0.52% 0.0-1.0% (p=0.002). The nominal differences in mean CGM glucose between the 110 mg/dl and the 130 mg/dl glucose targets (8 mg/dl in each case) were not statistically significant in either the IO or BH configuration (p>0.05). There was less hypoglycemia in the IO configuration, but not the BH configuration, when using the 130 mg/dl target vs. the 110 mg/dl target (p=0.03).
Conclusions: Both configurations of the BP provided safe and effective glycemic control using both glucose targets during home use. Hypoglycemia was lower with the BH configuration vs. the IO configuration using the 110 mg/dl target. Hypoglycemia was lower in the IO configuration when using the 130 mg/dl target vs. the 110 mg/dl target. Larger and longer studies will be needed to quantify differences in outcomes between the IO and BH configurations of the BP.
Disclosure
L. E. Castellanos: None. C. A. Balliro: Consultant; Self; Beta Bionics, Inc., Novo Nordisk. J. Sherwood: None. M. Tuffaha: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. F. El-khatib: Employee; Self; Beta Bionics, Inc., Stock/Shareholder; Self; Beta Bionics, Inc. E. Damiano: Other Relationship; Self; Beta Bionics, Inc., Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S. J. Russell: Advisory Panel; Self; Companion Medical, ConvaTec Inc., Consultant; Self; Beta Bionics, Inc., Novo Nordisk, Other Relationship; Self; Beta Bionics, Inc., Research Support; Self; Beta Bionics, Inc., Novo Nordisk, Zealand Pharma A/S.
To determine whether the bihormonal bionic pancreas (BHBP) improves glycemic control and reduces hypoglycemia in individuals with congenital hyperinsulinism (HI) and postpancreatectomy diabetes (PPD) ...compared with usual care (UC).
Ten subjects with HI and PPD completed this open-label, crossover pilot study. Coprimary outcomes were mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration <3.3 mmol/L.
Mean (SD) CGM glucose concentration was 8.3 (0.7) mmol/L in the BHBP period versus 9 (1.8) mmol/L in the UC period (
= 0.13). Mean (SD) time with CGM glucose concentration <3.3 mmol/L was 0% (0.002) in the BHBP period vs. 1.3% (0.018) in the UC period (
= 0.11).
Relative to UC, the BHBP resulted in comparable glycemic control in our population.
In an outpatient, home-use, random-order, controlled trial we compared automated glycemic control with the iLet bionic pancreas in the insulin-only (IOBP) vs. the bihormonal (BHBP) configurations for ...one week each in adult subjects (n=10) with type 1 diabetes. Subjects used their typical insulin analog (lispro or aspart) during both arms of the study. During the BHBP period the iLet delivered micro-doses of dasiglucagon, a glucagon analog stable in aqueous solution (Zealand Pharma). The insulin control algorithm was identical in both configurations, was initiated solely based on each subjects’ body mass without any information regarding patients’ baseline insulin needs, and used a glucose target of 110 mg/dl. The mean CGM glucose was lower in the BHBP arm vs. the IOBP arm (139±11 vs. 149±13 mg/dl, p=0.004) while the % of time with CGMG <54 mg/dl was nominally reduced (0.2%, IQR 0-0.4 vs. 0.6%, IQR 0.2-1.1%, p=0.11). We used an autoregressive time series model to determine statistical significance for differences between arms for each individual subject. Eight subjects had a significantly lower mean CGMG during the BHBP arm (p<0.05, mean improvement 12±7 mg/dl), while in the remaining two subjects there was no significant difference (nominal absolute difference 2±1 mg/dl). Eight of the ten subjects had a nominal reduction of the % of time <54 mg/dL in the BHBP arm (mean nominal difference -0.5%, range -0.1 to -1.0%), none of which were statistically significant. Here we demonstrated significant benefit of adding dasiglucagon in eight of ten subjects, allowing them to achieve a lower mean glucose without increased rates of hypoglycemia, in a trial comparing the BHBP and IOBP configurations of the iLet.
Disclosure
J. Sherwood: None. C.A. Balliro: None. R.Z. Jafri: None. L.E. Castellanos: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Greaux: None. H. Zheng: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.
Funding
Beta Bionics, Inc.
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