Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Frequency and Causes of Nocturnal Alarms in Youth and Young Adults With Type 1 Diabetes Using a First-Generation Hybrid Closed-Loop System.

Background: Meeting glycemic recommendations is challenging for youth with type 1 diabetes. Diabetes technology, including continuous glucose monitoring (CGM) and hybrid closed-loop (HCL) automated insulin delivery systems, significantly increase achievement of glycemic targets; however, many youth struggle to sustain use of early HCL systems. Nocturnal alarm fatigue contributes to disrupted sleep and device discontinuation. Methods: We examined the frequency and causes of nocturnal (10:00 p.m. to 6:00 a.m.) alarms in pediatric patients (N = 76, median age 14.5 years [interquartile range 11.8-17.0 years, range 7-24 years]) starting on a first-generation HCL system in a prospective observational study. Device data were analyzed with linear mixed-effects models to examine change across time at 3-month intervals for 12 months. Results: At baseline (HCL system in nonautomated mode), participants averaged 3.3 ± 0.6 alarms per night. In the 2 weeks after starting HCL (automated) mode, alarm frequency significantly increased to 5.4 ± 0.5 times per night (P <0.001). Alarm frequency decreased through the remainder of the observational period; however, CGM sensor and HCL system use also declined. The types of alarms were evenly distributed among sensor maintenance, sensor threshold, pump, and HCL-specific alarms. Conclusion: These data show that HCL system nocturnal alarms are frequent and may be barriers to sleep quality and device use. Further research is needed to assess the impact of diabetes technology on sleep and to determine method to improve sleep quality with technology use.

Friend or Foe: a Narrative Review of the Impact of Diabetes Technology on Sleep.

PURPOSE OF REVIEW: The purpose of this review is to present a review of sleep science, the relationship between sleep and type 1 diabetes, and highlight the current literature on sleep outcomes in adult and pediatric diabetes technology research. RECENT FINDINGS: Sleep quality is associated with glycemic outcomes, diabetes self-management, and mental health in people with type 1 diabetes. Diabetes technologies, including insulin pumps, continuous glucose monitors, and hybrid closed-loop systems improve glycemic outcomes. However, many people find this technology challenging for a variety of reasons, including increased burden and frequent alarms, especially during the night. The impact of different devices on sleep quality and quantity has been mixed. The newest technology, the hybrid closed-loop systems, offers the best opportunity for nocturnal glycemic regulation and has improved patient and family perspectives on sleep quality. However, objective sleep assessment has not shown significant improvement on sleep duration. Sleep quality and quantity in people with type 1 diabetes are widely recognized as an important component of health care, and the literature regarding the impact of diabetes devices on sleep is increasing. However, sleep disruptions are common and a barrier to device use. Despite finding minimal changes to sleep duration with device use, subjective accounts of sleep quality are overall positive, especially in those using hybrid closed-loop systems. Sleep quantity and quality are important outcomes to consider as diabetes technology continues to evolve.

Sleep in Type 1 Diabetes: Implications for Glycemic Control and Diabetes Management.

PURPOSE OF REVIEW: To highlight recent findings from studies of sleep in type 1 diabetes (T1D), with a focus on the role of sleep in self-management, the cognitive and psychosocial outcomes related to sleep disturbances, and factors associated with sleep disturbances specific to T1D. RECENT FINDINGS: People with T1D experience higher rates of sleep disturbances than people without diabetes, and these disturbances have negative implications for glycemic control and diabetes management, as well as psychosocial and cognitive outcomes. Inconsistent sleep timing (bedtime and wake time) has emerged as a potential target for interventions, as variability in sleep timing has been linked with poorer glycemic control and adherence to treatment. Sleep-promoting interventions and new diabetes technology have the potential to improve sleep in people with T1D. Sleep is increasingly considered a critical factor in diabetes management, but more multi-method and longitudinal research is needed. We emphasize the importance of sufficient and consistent sleep for people with T1D, and the need for providers to routinely assess sleep among patients with T1D.

Cyclic bisphosphonate therapy reduces pain and improves physical functioning in children with osteogenesis imperfecta.

BACKGROUND: Children with osteogenesis imperfecta (OI) experience pain and impaired physical functioning. The longitudinal effect of cyclic bisphosphonate treatment on these symptoms has not been described. We serially evaluated pain and functioning in pediatric patients with OI treated with intravenous bisphosphonate therapy. METHODS: Pain and physical functioning were assessed at multiple time-points over two infusion cycles in 22 OI patients (median age 10 years [range 2-21 years]; 8 girls) receiving cyclic intravenous bisphosphonate therapy. Pain was assessed using the FACES® visual analogue scale; physical functioning, including self-care, was assessed using the PedsQL™ Generic Core inventory. RESULTS: Pain scores decreased significantly immediately following infusion and remained reduced at 4 weeks post-infusion, increasing before and decreasing again after subsequent infusion (F = 25.00, p < 0.001). Physical functioning scaled scores improved 4 weeks after infusion and declined before subsequent infusion across patients (F = 10.87, p = 0.007). Exploratory analyses indicated significantly different effects between mild and moderate-severe OI types for pain, but not for physical functioning. No fractures occurred during the study. CONCLUSION: In children with OI, cyclic intravenous bisphosphonate therapy transiently reduces pain and improves functional abilities. Pain relief occurs immediately following infusion with functional improvements observed 4 weeks later. Both pain and physical functioning return to pretreatment levels by the subsequent infusion.

Accuracy of a Continuous Glucose Monitor During Pediatric Type 1 Diabetes Inpatient Admissions.

Objective: Continuous glucose monitors (CGMs) used for type 1 diabetes management are associated with lower hemoglobin A1c. CGMs are not approved for inpatient use, when close glucose monitoring and intensive insulin management are essential for optimal health. Accuracy data from adult hospitalizations have been published, but pediatric data are limited. Design and Methods: This retrospective review of Dexcom G6 data from youth with type 1 diabetes during hospitalization assessed CGMs and matched (within 5 min) point-of-care (POC) and laboratory glucose values. Glucose values >400 and <40 mg/dL were excluded due to sensor reporting capabilities. Standard methods for CGM accuracy were used including mean absolute relative difference (MARD), Clarke Error Grids, and percentage of CGM values within 15%/20%/30% if glucose value is >100 mg/dL and 15/20/30 mg/dL if value is ≤100 mg/dL. Results: A total of 1120 POC and 288 laboratory-matched pairs were collected from 83 unique patients (median age 12.0 years, 68.7% non-Hispanic white, 54.2% male) during 100 admissions. For POC values, overall, MARD was 11.8%, that on the medical floor was 13.5%, and that in the intensive care unit was 7.9%. The MARD for all laboratory values was 6.5%. In total, 98% of matched pairs were within Clarke Error Grid A and B zones. Conclusions: Findings from our pediatric population were similar to accuracy reported in hospitalized adults, indicating the potential role for CGM use during pediatric hospitalizations. Additional research is needed to assess accuracy under various conditions, including medication use, as well as development of safe hospital protocols for successful CGM implementation for routine inpatient care.

Accuracy of a Real-Time Continuous Glucose Monitor in Pediatric Diabetic Ketoacidosis Admissions.

Objective: Continuous glucose monitoring (CGM) devices are integral in the outpatient care of people with type 1 diabetes, although they lack inpatient labeling. Food and Drug Administration began allowing inpatient use during the coronavirus disease 2019 (COVID-19) pandemic, with some accuracy data now available, primarily from adult hospitals. Pediatric inpatient data remain limited, particularly during diabetic ketoacidosis (DKA) admissions and for patients receiving intravenous (IV) insulin. Design and Methods: This retrospective chart review compared point-of-care glucose values to personal Dexcom G6 sensor data during pediatric hospitalizations. Accuracy was assessed using mean absolute relative difference (MARD), Clarke Error Grids, and the percentage of values within 15/20/30% if glucose value >100 mg/dL and 15/20/30 mg/dL if glucose value ≤100 mg/dL. Results: Matched paired glucose values (N = 612) from 36 patients (median age 14 years, 58.3% non-Hispanic White, 47.2% male) and 42 inpatient encounters were included in this subanalysis of DKA admissions. The MARDs for DKA and non-DKA admissions (N = 503) were 11.8% and 11.7%, with 97.6% and 98.6% of pairs falling within A and B zones of the Clarke Error Grid, respectively. Severe DKA admissions (pH <7.15 and/or bicarbonate <5 mmol/L) had a MARD of 8.9% compared to 14.3% for nonsevere DKA admissions. The MARD during administration of IV insulin (N = 266) was 13.4%. Conclusions: CGM accuracy is similar between DKA and non-DKA admissions and is maintained in severe DKA and during IV insulin administration, suggesting potential usability in pediatric hospitalizations. Further study on the feasibility of implementation of CGM in the hospital is needed.

Impact of 6-months of an advanced hybrid closed-loop system on sleep and psychosocial outcomes in youth with type 1 diabetes and their parents.

INTRODUCTION: Youth with type 1 diabetes (T1D) and parents experience reduced quality of life and sleep quality due to nocturnal monitoring, hypoglycemia fear, and diabetes-related disruptions. This study examined the sleep and quality of life impact of advanced technology. METHODS: Thirty-nine youth with T1D, aged 2-17 years, starting an advanced hybrid closed-loop (HCL) system and a parent participated in an observational study. Surveys, actigraphy, sleep diaries, and glycemic data (youth) were captured prior to HCL, at one week, 3 months, and 6 months. Outcomes were modeled using linear mixed effects models with random intercepts to account for within-subject correlation, with least-squares means at each timepoint compared to baseline. RESULTS: Parents and youth reported improvements in health-related quality of life and fear of hypoglycemia after HCL initiation. Concurrently, nocturnal glycemia improved. Actigraphy-derived sleep outcomes showed improved 6 month adolescent efficiency and 3 and 6 month parent wake after sleep onset. Additionally, parents reported improved subjective sleep quality and child sleep-related impairment at 3 months. CONCLUSIONS: With nocturnal glycemic improvements in youth using HCL technology, some aspects of parent and youth sleep and quality of life improved. This may reflect decreased parental monitoring and worry and highlights benefits for youth beyond glycemia.

Patient reported outcomes (PROs) and user experiences of young children with type 1 diabetes using t:slim X2 insulin pump with control-IQ technology.

OBJECTIVE: Examine patient-reported outcomes (PROs) after the use of t:slim X2 insulin pump with Control-IQ technology (CIQ) in young children with type 1 diabetes. METHODS: Children with type 1 diabetes, ages 2 to < 6 years (n = 102), were randomly assigned 2:1 to either CIQ or standard care (SC) with pump or multiple daily injections (MDI) plus continuous glucose monitoring (CGM) for 13 weeks. Both groups were offered to use CIQ for an additional 13 weeks after the randomized control trial's (RCT) completion. Guardians completed PRO questionnaires at baseline, 13-, and 26-weeks examining hypoglycemia concerns, quality of life, parenting stress, and sleep. At 26 weeks, 28 families participated in user-experience interviews. Repeated measures analyses compared PRO scores between systems used. RESULT: Comparing CIQ vs SC, responses on all 5 PRO surveys favored the CIQ group, showing that CIQ was superior to SC at 26 weeks (p values < 0.05). User-experience interviews indicated significant benefits in optimized glycemic control overall and nighttime control (28 of 28 families endorsed). All but 2/28 families noted substantial reduction in management burden resulting in less mental burden and all but 4 stated that they wanted their children to continue using CIQ. CONCLUSIONS: Families utilizing CIQ experienced glycemic benefits coupled with substantial benefits in PROs, documented in surveys and interviews. Families utilizing CIQ had reduced hypoglycemia concerns and parenting stress, and improved quality of life and sleep. These findings demonstrate the benefit of CIQ in young children with type 1 diabetes that goes beyond documented glycemic benefit.

Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience.

Objectives: To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D. Research Design and Methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team. Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event. Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.

The future of telehealth in type 1 diabetes.

PURPOSE OF REVIEW: Although telemedicine and telehealth services have been a part of type 1 diabetes (T1D) clinical care for several decades, the expansion of in-home telemedicine during the COVID-19 pandemic significantly increased interest in long-term use as part of routine care. This review highlights the current literature regarding telemedicine in T1D care as well as the benefits and barriers to use in a postpandemic world. RECENT FINDINGS: Telemedicine has increased patient contact with healthcare providers, allowing for more frequent insulin dose adjustments and improvements in glycemic outcomes. In addition to routine clinical care, T1D device training and mental healthcare have been successful through telemedicine. Significant barriers to continued telemedicine care exist, including patient access and technology knowledge, language, and loss of face-to-face interaction. Healthcare providers additionally face unpredictable reimbursement and loss of continuity across state lines, and lack of resources and training for device downloads and telemedicine software. SUMMARY: Telemedicine can be successfully used in T1D care and has the potential to significantly impact glycemic and long-term outcomes. Due to continued interest for in-person visits by people with T1D and providers, it is likely that long-term telemedicine use will include a hybrid format.

Improvements in Parental Sleep, Fear of Hypoglycemia, and Diabetes Distress With Use of an Advanced Hybrid Closed-Loop System.

OBJECTIVE: Parental sleep quality may contribute to glycemic control in youth with type 1 diabetes. In this article we present sleep analysis from a multicenter, randomized trial of children ages 6-13 years with type 1 diabetes evaluating the Tandem Control-IQ (CIQ) hybrid closed-loop (HCL) system. RESEARCH DESIGN AND METHODS: Pittsburgh Sleep Quality Index (PSQI) scores were assessed at baseline to identify parents as "poor" sleepers (PSQI >5). Glycemic and psycho-behavioral outcomes before and after CIQ use were analyzed in poor sleepers (n = 49) and their children. RESULTS: Nocturnal time in range (P < 0.001) and time hyperglycemic (P < 0.001), Hypoglycemia Fear Survey for Parents score (P < 0.001), Problem Areas in Diabetes scale score (P < 0.001), PSQI score (P < 0.001), and Hypoglycemia Fear Survey for Children score (P = 0.025) significantly improved. Of poor sleepers, 27 became good sleepers (PSQI score <5). CONCLUSIONS: Use of CIQ in youth with type 1 diabetes ages 6-13 years significantly improved sleep and psychosocial measures in parent poor sleepers, coinciding with improvements in child nocturnal glycemia, highlighting the relationship between HCL systems and parent sleep quality.

Diabetes Technology Use in Remote Pediatric Patients with Type 1 Diabetes Using Clinic-to-Clinic Telemedicine.

Background: Clinic-to-clinic telemedicine can increase visit frequency in pediatric patients with type 1 diabetes (T1D) living far from a diabetes specialty clinic, but the impact on adoption of diabetes technology is unclear. Materials and Methods: Pediatric patients with T1D in Colorado and surrounding states who received diabetes care using clinic-to-clinic telemedicine were enrolled. Medical records and surveys were reviewed to ascertain technology use, and data were compared to patients from the main clinic population. Results: Patients (N = 128, baseline mean age 12.4 ± 4.2 years, median T1D duration 3.3 years [IQR 1.4-7.7], mean A1c 8.9% ± 1.8%, 60% male, 75% non-Hispanic white, 77% private insurance) who utilized telemedicine were included. Technology use among telemedicine patients was not associated with gender, T1D duration, insurance, distance from the main clinic or rural designation but was associated with ethnicity and A1c. Compared to the main clinic cohort (N = 3636), continuous glucose monitor (CGM) use and pump/CGM combination use was lower among patients participating in clinic-to-clinic telemedicine (CGM: 29.7% vs. 56.0%, P < 0.001; CGM/pump combination: 27.3% vs. 40.3%, P = 0.004). Technology use was associated with lower A1c regardless of cohort. Conclusions: Compared to patients attending in-person clinic, pediatric T1D patients who use clinic-to-clinic telemedicine due to their distance from the main clinic, have lower CGM and combination CGM/pump use. For both telemedicine and main clinic patients, CGM and CGM/pump combination was associated with lower A1c. Additional research is needed to explore reasons for this discrepancy and find methods to improve CGM use in this population.

Safety and Glycemic Outcomes With a Tubeless Automated Insulin Delivery System in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Clinical Trial.

OBJECTIVE: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population. RESEARCH DESIGN AND METHODS: A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy. RESULTS: There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204). CONCLUSIONS: Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.

Accuracy of a breath ketone analyzer to detect ketosis in adults and children with type 1 diabetes.

OBJECTIVE: To assess the accuracy of a breath ketone analyzer to detect ketosis in adults and children with type 1 diabetes. RESEARCH DESIGN AND METHODS: This is a proof-of-concept, prospective study comparing breath ketone analyzer and blood ketone meter to detect ketosis. RESULTS: A total of 500 measurements from 19 adults and children with type 1 diabetes were analyzed. There was a significant association between the breath ketone analyzer and blood ketone meter results in non-fasting adults (p = 0.0066), but not in children (p = 0.4579). In adults, a cut-off of 3.9 PPM on the breath ketone analyzer maximized the Youden Index with an AUC of 0.73. This cut-off for the breath ketone analyzer had 94.7% sensitivity and 54.2% specificity to detect ketosis (≥0.6 mmol/L in blood ketone meter). CONCLUSIONS: The breath ketone analyzer may be considered as a non-invasive screening tool to rule out ketosis in adults with type 1 diabetes.

Real-World Use of a New Hybrid Closed Loop Improves Glycemic Control in Youth with Type 1 Diabetes.

Objective: To describe real-world outcomes for youth using the Tandem t:slim X2 insulin pump with Control-IQ technology ("Control-IQ") for 6 months at a large pediatric clinic. Methods: Youth with type 1 diabetes, who started Control-IQ for routine care, were prospectively followed. Data on system use and glycemic control were collected before Control-IQ start, and at 1, 3, and 6 months after start. Mixed models assessed change across time; interactions with baseline hemoglobin A1c (HbA1c) and age were tested. Results: In 191 youth (median age 14, 47% female, and median HbA1c 7.6%), percent time with glucose levels 70-180 mg/dL (time-in-range [TIR]) improved from 57% at baseline to 66% at 6 months (P < 0.001). The proportion of participants reaching TIR target (>70%) doubled from 23.5% at baseline to 47.8% at 3 months, sustaining at 46.7% at 6 months (P < 0.001). Glucose management indicator (approximation of HbA1c) improved from 7.5% at baseline to 7.1% at 3 months and 7.2% at 6 months (P < 0.001). Those with higher baseline HbA1c experienced the most substantial improvements in glycemic control. Percent time using the Control-IQ feature was 86.4% at 6 months, and <4% of cohort discontinued use. Conclusion: The Control-IQ system clinically and significantly improved glycemic control in a large sample of youth. System use was high at 6 months, with only a small proportion discontinuing use, indicating potential for sustaining results long term.

Health-Related Quality of Life and Treatment Satisfaction in Parents and Children with Type 1 Diabetes Using Closed-Loop Control.

Introduction: Hybrid closed-loop systems increase time-in-range (TIR) and reduce glycemic variability. Person-reported outcomes (PROs) are essential to assess the utility of new devices and their impact on quality of life. This article focuses on the PROs for pediatric participants (ages 6-13 years) with type 1 diabetes (T1D) and their parents during a trial using the Tandem Control-IQ system, which was shown to increase TIR and improve other glycemic metrics. Research Design and Methods: One hundred and one children 6 to 13 years old with T1D were randomly assigned to closed-loop control (CLC) or sensor-augmented pump (SAP) in a 16-week randomized clinical trial with extension to 28 weeks during which the SAP group crossed over to CLC. Health-related quality of life and treatment satisfaction measures were obtained from children and their parents at baseline, 16 weeks, and 28 weeks. Results: Neither the children in the CLC group nor their parents had statistically significant changes in PRO outcomes compared with the SAP group at the end of the 16-week randomized controlled trial and the 28-week extension. Parents in the CLC group reported nonsignificant improvements in some PRO scores when compared with the SAP group at 16 weeks, which were sustained at 28 weeks. Sleep scores for parents improved from "poor sleep quality" to "adequate sleep quality" between baseline and 16 weeks, however, the change in scores was not statistically different between groups. Conclusions: Children with T1D who used the Control-IQ system did not experience increased burden compared with those using SAP based on person-reported outcomes from the children and their parents. Clinical Trials Registration: NCT03844789.

First Outpatient Evaluation of a Tubeless Automated Insulin Delivery System with Customizable Glucose Targets in Children and Adults with Type 1 Diabetes.

Background: The objective of this study was to assess the safety and effectiveness of the first commercial configuration of a tubeless automated insulin delivery system, Omnipod® 5, in children (6-13.9 years) and adults (14-70 years) with type 1 diabetes (T1D) in an outpatient setting. Materials and Methods: This was a single-arm, multicenter, prospective clinical study. Data were collected over a 14-day standard therapy (ST) phase followed by a 14-day hybrid closed-loop (HCL) phase, where participants (n = 36) spent 72 h at each of three prespecified glucose targets (130, 140, and 150 mg/dL, 9 days total) then 5 days with free choice of glucose targets (110-150 mg/dL) using the Omnipod 5. Remote safety monitoring alerts were enabled during the HCL phase. Primary endpoints were difference in time in range (TIR) (70-180 mg/dL) between ST and HCL phases and proportion of participants reporting serious device-related adverse events. Results: Mean TIR was significantly higher among children in the free-choice period overall (64.9% ± 12.2%, P < 0.01) and when using a 110 mg/dL target (71.2% ± 10.2%, P < 0.01), a 130 mg/dL target (61.5% ± 7.7%, P < 0.01), and a 140 mg/dL target (64.8% ± 11.6%, P < 0.01), and among adults using a 130 mg/dL target (75.1% ± 11.6%, P < 0.05), compared to the ST phase (children: 51.0% ± 13.3% and adults: 65.6% ± 15.7%). There were no serious device-related adverse events reported during the HCL phase, nor were there episodes of severe hypoglycemia or diabetic ketoacidosis. Conclusion: The Omnipod 5 System was safe and effective when used at glucose targets from 110 to 150 mg/dL for 14 days at home in children and adults with T1D.