The landmark Diabetes Control and Complications Trial (DCCT) showed that glucose control is critical to reducing the risk of diabetes-related complications. This chapter outlines a series of innovations and investigations that followed the DCCT, aimed at minimizing the risk of hypoglycemia while further improving glucose control. The chapter presents an example of innovations in wired enzyme technology that facilitated the movement from capillary glucose monitoring to continuous glucose monitoring (CGM) and ultimately, the first-factory calibrated CGM system. The next glycemic management innovation was to connect CGM data to an insulin pump containing an algorithm able to adjust insulin delivery based on the changing glucose levels and trends. The key features of automated insulin delivery (AID) systems, currently approved in the United States, are presented. The AID summary table includes type of pump, type and function of the insulin delivery algorithm, the data management system, and the indications for use. The next section explores the innovation of alternative routes of insulin delivery to move toward the goal of a fully automated insulin delivery system. The main trials in developing and implementing an implantable intraperitoneal programmable system are summarized. The last section explores if sensor input in addition to glucose levels such as continuous sensing of ketone, lactate, or insulin levels may provide valuable feedback to move us closer to a fully autonomous AID system. Much of this diabetes innovation and investigation work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases over that last 75 years.

Disclosure: S.J. Russell: Beta Bionics. R.R. Selagamsetty,: Beta Bionics. C.S. Balliro: Beta Bionics. E. Damiano: Beta Bionics. Background: The iLet bionic pancreas is an automated insulin delivery system that is initialized with only body weight. The only user input is meal announcements without carbohydrate counting. Meals and snacks are announced as a type (Breakfast, Lunch, or Dinner) and a relative size for that type (Usual for me, More, or Less). The iLet then autonomously determines the size of meal doses. All basal and correction insulin is determined autonomously by the iLet, which adapts continuously to changing insulin needs. The only input from the health care provider is the glucose target profile. Objective: The objective of this analysis was to assess the association between the number of meals announced by the user per day on one hand, and the frequency of user interaction with the iLet (determine by number of swipes to unlock the iLet) on the other, on continuous glucose monitoring (CGM) outcomes during real-world use of the iLet bionic pancreas by adults (≥18 years of age) during the first 18 months after FDA clearance. This analysis was undertaken with the goal of providing users and health care providers information they can use to obtain the best glycemic control from the iLet. Methods: Commercial users of the iLet who had a pre-iLet HbA1c value available and at least 3 weeks of iLet data in the cloud (n=5,987) were included in the analysis. Glucose management indicator (GMI) values and percentage of time in ranges (%70-180 mg/dl, %<70 mg/dl, and %<54 mg/dl) were calculated from all available CGM data. Users were classified according to the average number of meal announcements per day (MPD; from <0.5 to ≥4.5 per day in 0.5 meal increments) and separately according to the number of swipes to unlock the (STU; ≤4, 4-<13, and ≥13 swipes to unlock per day). Results: Mean baseline HbA1c was 8.6%; mean iLet GMI was 7.2%. Groups with <2.5 MPD had higher GMI and lower %70-180 mg/dl than those with ≥2.5 MPD. Groups with ≥2.5 to <4.5 MPD all had similar outcomes, with lower GMI and higher %70-180 mg/dl than groups with <2.5 MDP. There was little difference in %<70 mg/dl and %<54 mg/dl from <0.5 to <4.5 MPD. The ≥4.5 MPD group had lower GMI and higher %70-180 mg/dl than others, but it also had higher %<70 mg/dl and %<54 mg/dl. GMI and %<54 mg/dl was similar for all levels of STU. Higher STU was associated with higher %70-180 mg/dl and higher %<70 mg/dl. Discussion/Conclusion: In users of the iLet bionic pancreas the best outcomes were achieved by those announcing 2.5 to <4.5 MPD. This may correspond to typical numbers of meals and snacks consumed by users. Announcement of ≥4.5 MPD was associated with lower GMI and higher %70-180 mg/dl, but also higher %<54 mg/dl. Users announcing ≥4.5 MPD may be announcing “ghost” meals to obtain correction insulin, which risks “stacking” on top of iLet-determined correction doses and may lead to increased hypoglycemia. Higher STU was associated with higher %70-180 mg/dl and %<70 mg/dl but little difference in GMI and %<54 mg/dl. Presentation: Monday, July 14, 2025

Introduction and Objective: To analyze the impact of the iLet bionic pancreas on glycemic control in users with type 1 and type 2 diabetes during the first 18 months after FDA clearance (note that the iLet is not currently indicated for use in people with type 2 diabetes). Methods: Commercial users of the iLet who had a pre-iLet HbA1c value available and had at least 3 weeks of iLet data in the cloud were included. Baseline HbA1c values were compared with the glucose management indicator (GMI) values calculated from all available continuous glucose monitoring (CGM) data, both reported as mean±SD [IQR]. Users with type 1 and type 2 diabetes were analyzed separately. The percentage of time with CGM glucose <54 mg/dl during iLet use was calculated for all groups and reported as median [IQR]. The insulin total daily dose per body mass (TDD) was calculated for all groups and reported as mean±SD [IQR]. Results: Data from 6,992 commercial users (5,843 with type 1 and 1,012 with type 2 diabetes) were included in the analysis. Users with type 1 diabetes had a baseline HbA1c of 8.7±2.0% [7.2-9.7] and an iLet GMI of 7.3±0.5% [7.0-7.5] (difference: -1.4%). Users with type 2 diabetes had a baseline HbA1c of 9.1±2.0% [7.7-10.2] and an iLet GMI of 7.4±0.6% [7.0-7.6] (difference: -1.7%). The time with CGM glucose <54 mg/dl was 0.3% [0.1-0.7] in users with type 1 diabetes and 0.1% [0.0-0.2] in users with type 2 diabetes. The insulin TDD was 0.8±0.3 U/kg/day [0.6-1.0] in users with type 1 diabetes and 0.9±0.4 U/kg/day [0.6-1.1] in users with type 2 diabetes. Conclusion: The baseline HbA1c values for users with type 2 diabetes were higher, and the decreases from baseline HbA1c to iLet GMI values were larger, than among users with type 1 diabetes. The iLet GMI values achieved by users and insulin TDD per body mass with both type 1 and type 2 diabetes were similar. The time spent <54 mg/dl was lower in users with type 2 diabetes than those with type 1 diabetes. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. R. Selagamsetty: Employee; Beta Bionics, Inc. E. Damiano: Other Relationship; Beta Bionics, Inc. Beta Bionics, Inc.

Introduction and Objective: To analyze the impact of the iLet bionic pancreas on glycemic control during the first 18 months after FDA clearance and compare to the results of the Bionic Pancreas Pivotal Trial (BPPT). Methods: Commercial users of the iLet who had a pre-iLet HbA1c value available and had at least 3 weeks of iLet data in the cloud were included. Baseline HbA1c values were compared with the glucose management indicator (GMI) values calculated from all available continuous glucose monitoring (CGM) data, both reported as mean±SD [IQR]. Adults (≥18 years) and children were analyzed separately. Data from the BPPT were analyzed in the same way for comparison. The percentage of time with CGM glucose <54 mg/dl during iLet use was calculated for all groups and were reported as median [IQR]. Results: Data from 6,992 commercial users (5,987 adults and 1,005 children) were included in the real-world analysis, and from 330 participants (218 adults and 112 children) in the BPPT analysis. Adult commercial users had a baseline HbA1c of 8.6±1.9% [7.2-9.6] and an iLet GMI of 7.2±0.5% [7.0-7.4] (difference: -1.4%), compared to 7.7±1.2% [6.9-8.3] and 7.0±0.3% [6.9-7.2], respectively, in the BPPT (difference: -0.7%). Pediatric commercial users had a baseline HbA1c of 9.5±2.2% [7.7-10.8] and an iLet GMI of 7.7±0.6% [7.3-8.0] (difference: -1.8%), compared to 8.1±1.2% [7.3-8.9] and 7.4±0.3% [7.2-7.5], respectively, in the BPPT (difference: -0.7%). The time with CGM glucose <54 mg/dl was 0.3% [0.1-0.6] in adults and 0.3% [0.1-0.6] children in commercial use and 0.3% [0.1-0.5] in adults and 0.3% [0.2-0.6] in children in the BPPT. Conclusion: The baseline HbA1c values of commercial users were higher, and the decreases from baseline HbA1c to iLet GMI values were larger than among participants in the BPPT. The time spent <54 mg/dl were comparable in both settings. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. R. Selagamsetty: Employee; Beta Bionics, Inc. E. Damiano: Other Relationship; Beta Bionics, Inc. Beta Bionics, Inc.

The iLet Bionic Pancreas system can improve glycemia in individuals with type 1 diabetes with its simple interface, setup, and maintenance, making it practical for use in the primary care setting and via telehealth (TH). This multisite, random-order crossover trial included 40 adults with type 1 diabetes who received care either from an endocrinology or a primary care clinic and were seen either in person or via TH. Of these 40 participants, 97% achieved an average glucose (AG) <183 mg/dL, and 64% achieved an AG <154 mg/dL. These results suggest that the system can be initiated effectively by primary care providers and via TH, potentially expanding access to this technology to a broad population, including individuals who cannot easily access subspecialty diabetes care.

Objective: 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 cross-over trial (NCT #03258853). Research Design and Methods: Twenty participants with CFRD were assigned in random-order to 14-days each on the BP or their usual diabetes 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 (TIR) on days 3-14 of each arm, and key secondary outcomes included mean CGM glucose and the percent time sensor-measured glucose was in hypoglycemic range <54 mg/dL. Results: TIR was significantly higher in the BP arm compared to the UC arm (75±11 versus 62±22%, p=0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150±19 mg/dL versus 171±45 mg/dL, p=0.007). There was no significant difference in percent time with sensor-measured glucose <54 mg/dL (0.27% versus 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. Conclusions: Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared to their UC, suggesting this may be an important therapeutic option for this patient population.

It is well established that glycemic and continuous glucose monitoring (CGM) outcomes improve with increasing user engagement for both therapeutic devices (insulin pumps and pens) and diagnostic devices (CGMs, flash-glucose monitors, and blood-glucose monitors) used in the management of type 1 diabetes (T1D). Unlike any other insulin-delivery device, the iLet Bionic Pancreas (BP) determines and delivers 100% of all therapeutic insulin. Given this degree of autonomy, we hypothesized that glycemic and CGM outcomes obtained by the BP might be independent of the frequency of user engagement. To that end, data about user interactions with the BP were captured on the BP during the Bionic Pancreas Pivotal Trial (BPPT), and analyzed retrospectively. The average frequency of meal announcements initiated by each participant using the BP, and the average frequency of swipe gestures to unlock the lock screen of the BP, were analyzed and taken as proxies for user engagement with the device. Among 219 adults with T1D who used the BP for 13 weeks during the BPPT, the mean CGM glucose level was 156 ± 12 mg/dl. The average number of meal announcements and swipes to unlock the screen were 2.8/day and 9.9/day, respectively. The slope and intercept of the linear correlation between the mean CGM glucose level and the average number of daily swipes to unlock the screen were -0.08 and 157 mg/dl, respectively. The R2 correlation coefficient was 0.00. Similarly, the slope and intercept of the linear correlation between the mean CGM glucose level and the average number of daily meal announcements were -0.27 and 163 mg/dl, respectively, with an R2 of 0.06. Similar results to these are obtained when using 13-week HbA1c as an outcome. Unlike other therapeutic and diagnostic devices used in T1D management, glucose control achieved by the BP is nearly independent of the frequency of user engagement in terms of the metrics studied here. E. Damiano: Board Member; Beta Bionics, Inc. Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. R. Selagamsetty: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. R. Brandt: Employee; Beta Bionics, Inc. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. Other Relationship; Beta Bionics, Inc. Consultant; Beta Bionics, Inc. Research Support; Beta Bionics, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk.

Introduction & Objective: While about half of US adults with T1D are managed by primary care (PC), automated insulin delivery (AID) use is rare in PC compared to endocrinology (EN). The iLet Bionic Pancreas (BP) has a unique initiation process of simply entering the user’s weight, followed by perpetual autonomous adaptation to meet each user’s changing insulin needs; the BP may thus be more feasible for PC and/or telehealth (TH) deployment than AID systems with more intensive startup and follow-on care. This random order crossover trial (NCT05168657) evaluated feasibility of BP startup and management by PC versus EN and training via TH versus in person (IP). Methods: Forty adults with T1D (20 at a PC site, 20 at an EN site) were assigned to complete two study arms (14 days of BP use, 14 days of their usual diabetes care [UC]) in random order. PC participants’ UC was required to be multiple daily injections with or without CGM; EN participants’ UC was CGM sensor augmented pump. Half of each group were trained and managed by IP visits and half by TH. Primary outcome: % of each group achieving average glucose (AG) <183 mg/dL during BP use. Results: Both arms were completed by 39 participants. With BP use, 38 (97.4%) achieved AG <183 mg/dL, with no differences between PC and EN groups or the respective IP and TH subgroups (all p>0.05). Decreased AG was seen with BP use compared to UC in all four groups (all p<0.05). With BP use, PC and EN groups achieved similar results in AG, time <70, time between 70 and 180, time >180, and time >250 mg/dL. The PC group had slightly lower CV and time <54 mg/dL than EN with BP use (both p=0.03). There were no severe adverse events during BP or UC use. Conclusion: Training and initiation of the BP by PC and EN subspecialists, and through IP versus TH visits, resulted in similar CGM outcomes with the BP, which were improved relative to UC. These findings suggest that the BP, with its uniquely simple initiation, use, and follow-on care, may expand AID access for people limited by geographic and/or subspecialty access. Disclosure S. Oser: Other Relationship; American Diabetes Association, Association of Diabetes Care & Education Specialists. Research Support; Abbott. Advisory Panel; Dexcom, Inc., Jaeb Center for Health Research. M.S. Putman: Research Support; Dexcom, Inc. Other Relationship; Vertex Pharmaceuticals Incorporated. Research Support; Vertex Pharmaceuticals Incorporated. Advisory Panel; Anagram Therapeutics. E. Westfeldt: None. K.B. Huss: None. B. Prince: None. D.L. Buss: None. J.K. Oser: None. C.M. Lyon: None. M. O'Connor: None. A. Sabean: None. A. Ashley: None. E. Greaux: None. R. Bartholomew: None. S. Gaston: None. N. Anandakugan: None. C. Balliro: Employee; Beta Bionics, Inc. M.A. Hillard: Employee; Beta Bionics, Inc. S.J. Russell: Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. Other Relationship; Beta Bionics, Inc. Consultant; Beta Bionics, Inc. Research Support; Beta Bionics, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Other Relationship; Novo Nordisk. E. Damiano: Board Member; Beta Bionics, Inc. Employee; Beta Bionics, Inc. Stock/Shareholder; Beta Bionics, Inc. T. Oser: Research Support; Abbott. Advisory Panel; Medscape. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2107-04767)

Continuous glucose monitors (CGMs) have transformed the way people with type 1 diabetes can self-monitor glucose levels. Past studies have evaluated the accuracy of CGMs in clinic-based studies, but few have analyzed their accuracy in real-world settings. The Insulin-Only Bionic Pancreas Trial provided the opportunity to assess real-world accuracy of the blinded Dexcom G6 Pro sensor over the first 48-60 h of wear using a blood glucose meter (BGM) as a comparator for 1073 CGM-BGM pairs across 53 participants. The mean absolute relative difference (MARD) was 11.0% over a median period of 50 h (range 47-79 h). The MARD was 13.6% in the first 12 h, 10.5% in hours 12-24, and 10.1% after the first 24 h. These results are comparable with accuracy shown previously with laboratory-based measurements and provide real-world evidence of Dexcom G6 Pro accuracy, which improved after the first 12 h and then remained stable thereafter. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Objective: To evaluate the psychosocial impact and user experience for the insulin-only configuration of iLet bionic pancreas (BP) in persons 6-83 years years of age with type 1 diabetes. Research Design and Methods: In this multicenter, randomized controlled, 13-week trial, 275 adults (221 randomly assigned to the BP group and 54 to the standard of care [SC] group) and 165 youth and their caregivers (112 randomly assigned to the BP group and 53 to the SC group) completed psychosocial questionnaires at baseline, mid-study, and the end of the trial. Results: In all age groups, most participants would recommend using the BP, including those with previous experience using automated insulin delivery devices. Similarly, the vast majority of participants reported a high level of perceived benefits and a low number of perceived burdens. Adult participants reported significant decreases in the fear of hypoglycemia and in diabetes-specific emotional distress, as well as improvements in their perceived well-being. Conclusion: Findings demonstrate acceptability, reduced burden, and positive psychosocial outcomes for adults. Children and teenagers also report high acceptability and reduced burden, but less clear improvements in psychosocial outcomes. Clinical Trial Registration Number: NCT04200313.

Objective: We evaluated the performance of the iLet® bionic pancreas (BP) in non-Hispanic Whites (‘Whites’) and in Blacks, Hispanics, and others (‘Minorities’). Research Design and Methods: A multicenter, randomized controlled trial evaluated glycemic management with the BP versus standard-of-care (SC) in 161 adult and 165 pediatric participants with type 1 diabetes over 13 weeks. Results: In Whites (N=240), the mean baseline-adjusted difference in 13-week HbA1c between the BP and SC groups was -0.45% (95% CI -0.61% to -0.29% [-4.9, -6.6 to -3.1 mmol/mol]; P<0.001), while this difference among Minorities (N=84) was -0.53% (-0.83% to -0.24% [-6.0, -9.2 to -2.8 mmol/mol]; P<0.001). In Whites, the mean baseline-adjusted difference in TIR between the BP and SC groups was 10% (7 to 12%; P<0.001), while in Minorities it was 14% (10 to 18%; P<0.001). Conclusions: The BP improves glycemic control in both Whites and Minorities and offers promise in decreasing health care disparities.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using fast-acting insulin aspart (Fiasp®) in adults with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized trial, 275 adults with T1D (18-83 years old, baseline HbA1c 5.3%-14.9%) were randomly assigned 2:2:1 to use the BP with fast-acting insulin aspart (BP-F group, N = 114), BP with aspart or lispro (BP-A/L group, N = 107), or a control group using their standard-care insulin delivery (SC group, N = 54) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. The BP-F versus SC comparison was considered primary and BP-F versus BP-A/L secondary. Results: Mean ± standard deviation (SD) HbA1c decreased from 7.8% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP-F versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% CI -0.7 to -0.3, P < 0.001). CGM-measured percent time <54 mg/dL over 13 weeks with BP-F was noninferior to SC (adjusted difference = 0.00%, 95% CI -0.07 to 0.05, P < 0.001 for noninferiority based on a prespecified noninferiority limit of 1%). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 14% (3.4 h/day) and mean CGM glucose was reduced by 18 mg/dL with BP-F compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and the SD of CGM glucose all favored BP-F compared with SC (P < 0.001). Differences between BP-F and BP-A/L were minimal, with no difference in HbA1c at 13 weeks (adjusted difference = -0.0%, 95% CI -0.2 to 0.1, P = 0.67) or mean glucose (adjusted difference = -2.0 mg/dL, 95% CI -4.3 to 0.4, P = 0.10). Mean TIR was 2% greater with BP-F than BP-A/L (95% CI 1 to 4, P = 0.005), but the percentages of participants improving TIR by ≥5% were not significantly different (P = 0.49) and there were no significant differences comparing BP-F versus BP-A/L across nine patient-reported outcome surveys. The rate of severe hypoglycemia events did not differ among the three groups. Conclusions: In adults with T1D, HbA1c was improved with the BP using fast-acting insulin aspart compared with standard care without increasing CGM-measured hypoglycemia. However, the effect was no better than the reduction observed with the BP using aspart or lispro. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

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) &lt;60 mg/dl for more than minutes (McNemar's Test) . Secondary endpoints included the area over the glucose curve and &lt;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&lt;60 mg/dl in either the BH or IO configurations; AOC &lt;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 &lt;60 mg/dl for more than minutes; no subjects had an event using the BH configuration (p=0.25) . Median AOC &lt;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)

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.2%; 35% using multiple daily injections, 36% using an insulin pump without automation, 4% using an insulin pump with low glucose suspend, and 25% using a hybrid closed-loop system before the study) were randomly assigned 2:1 to use BP (n = 112) with insulin aspart or insulin lispro (BP group) or to a control group (n = 53) using their personal standard care insulin delivery (SC group) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 8.1% ± 1.2% at baseline to 7.5% ± 0.7% at 13 weeks with BP versus 7.8% ± 1.1% at both baseline and 13 weeks with SC (adjusted difference = -0.5%, 95% CI -0.7% to -0.2%, P < 0.001). Participants with baseline HbA1c ≥9.0% (n = 34) decreased mean HbA1c from 9.7% ± 0.8% to 7.9% ± 0.6% after 13 weeks with BP compared with 9.7% ± 0.5% to 9.8% ± 0.8% with SC. Over 13 weeks, mean time in range (TIR) 70-180 mg/dL increased by 10% (2.4 h per day) and mean CGM glucose was reduced by 15 mg/dL with BP compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose favored BP (P < 0.001). Time <54 mg/dL was low at baseline (median 0.2%) and not significantly different between groups over 13 weeks (P = 0.24). A severe hypoglycemia event occurred in 3 (2.7%) participants in the BP group and in 1 (1.9%) in the SC group. Conclusions: In youth 6-17 years old with T1D, use of insulin-only configuration of BP improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Improvement in glycemic metrics was most pronounced in participants with high baseline HbA1c levels. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Objective: To evaluate a transition from standard-of-care (SC) management of type 1 diabetes (any insulin delivery method including hybrid closed-loop systems plus real-time continuous glucose monitoring [CGM]) to use of the insulin-only configuration of the iLet® bionic pancreas (BP) in 90 adults and children (age 6-71 years). Research Design and Methods: After the SC group completed the randomized controlled trial (RCT) portion of the Insulin-Only BP Pivotal Trial, 90 of the 107 participants participated in a 13-week study using the BP. The key outcomes were change from baseline in HbA1c and CGM metrics after 13 weeks on the BP. Results: Using the BP, mean HbA1c decreased from 7.7% ± 1.0% (61 ± 10.9 mmol/mol) at baseline to 7.1% ± 0.6% (54 ± 6.6 mmol/mol) at 13 weeks (mean change -0.55% ± 0.72% [-6 ± 7.9 mmol/mol], P < 0.001), time in range 70-180 mg/dL increased by 12.0% ± 12.5% (from 53% ± 17% to 65% ± 9%, P < 0.001), and mean glucose decreased by -18 ± 23 mg/dL (from 182 ± 32 to 164 ± 15 mg/dL, P < 0.001). The higher the baseline HbA1c level, the greater the change in HbA1c. Results were similar in the adult (N = 42) and pediatric (N = 48) cohorts. Time <70 mg/dL decreased from baseline over the 13 weeks by -0.50% ± 1.86% (P = 0.02), and time <54 mg/dL was similar (change from baseline -0.08% ± 0.59%, P = 0.24). Two severe hypoglycemia events (in same participant) and one diabetic ketoacidosis event occurred. Conclusions: Glycemic control improved after adult and pediatric participants in the SC arm in the Insulin-Only BP Pivotal Trial transitioned to use of the BP. Improvement using the BP was of similar magnitude to that observed during the RCT. ClinicalTrials.gov number, NCT04200313.