Concordance of Blood Glucose and CGM During a Pilot Trial of Automated Insulin Delivery in Type 1 Diabetes Pregnancies.

Background: Customized and standard automated insulin delivery (AID) systems for use in pregnancies of women with preexisting type 1 diabetes (T1D) are being developed and tested to achieve pregnancy appropriate continuous glucose monitoring (CGM) targets. Guidance on the use of CGM for treatment decisions during pregnancy in the United States is limited. Methods: Ten pregnant women with preexisting T1D participated in a trial evaluating at-home use of a pregnancy-specific AID system. Seven-point self-monitoring of blood glucose (SMBG) was compared to the closest sensor glucose (Dexcom G6 CGM) value biweekly to assess safety and reliability based on the 20%/20 mg/dL criteria. Results: All participants completed the study with 7 participants satisfying the safety and reliability criteria with a mean absolute relative difference of 10.3%. Three participants did not fulfill the criteria, mainly because the frequency of SMBG did not meet the requirements. Conclusion: Dexcom G6 CGM is safe and accurate in the real-world setting for use in pregnant women with preexisting T1D with reduced SMBG testing as part of a pregnancy-specific AID system.

The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review.

Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These formulations have been shown to confer significant benefits in achieving good glycemic control with reduced hypoglycemia risk, weight loss, and cardiorenal protection. Therefore, it is reasonable to question whether there is still a role for insulin therapy in the management of type 2 diabetes. However, there are clear limitations inherent to GLP-1 RA therapy, including high rates of suboptimal adherence and treatment discontinuation due to high cost and side effects, which diminish long-term efficacy, and supply issues. In addition, newer formulations have shown improvements in convenience and tolerability, and have been shown to be even more effective when used in conjunction with basal insulin. In this narrative review, we discuss current evidence that supports GLP-1 RA use in combination with insulin therapy and the potential pitfalls of reliance on GLP-1 RAs as a substitute for insulin therapy.

Diabetes Technology Meeting 2023.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Performance of the Dexcom G7 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.

Beneficial Effects of Control-IQ Automated Insulin Delivery in Basal-Bolus and Basal-Only Insulin Users With Type 2 Diabetes.

The t:slim X2 insulin pump with Control-IQ technology (Control-IQ) advanced hybrid closed-loop automated insulin delivery system was evaluated in this prospective single-arm trial. Thirty adults with type 2 diabetes using the Control-IQ system showed substantial glycemic improvement with no increase in hypoglycemia. Mean time in range (70-180 mg/dL) improved 15%, representing an increase of 3.6 hours/day, and mean glucose decreased by 22 mg/dL.

Two Years with a Tubeless Automated Insulin Delivery System: A Single-Arm Multicenter Trial in Children, Adolescents, and Adults with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6-13.9 years) and adolescents/adults (14-70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140.

Use of Continuous Glucose Monitors Upon Hospital Discharge of People With Diabetes: Promise, Barriers, and Opportunity.

Continuous glucose monitors (CGMs) have increasingly been used in ambulatory and inpatient or hospital settings to improve glycemic outcomes for people with diabetes. Given their capacity to aid individuals in avoiding hypo- and hyperglycemia, they may also be useful when transitioning from hospital to home by reducing rates of hospital readmissions and emergency department visits. Several types of barriers presently exist that make the deployment of CGMs at the time of hospital discharge problematic, including (1) regulatory, (2) behavioral, (3) logistical, (4) technical, (5) staffing, and (6) systemic issues. In this commentary, we review the literature, discuss these barriers, and propose possible solutions to facilitate the use of CGMs in people with diabetes at the time of hospital discharge.

RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.

Treatment for type 1 diabetes (T1D) requires stimulation of functional ß cell regeneration and survival under stress. Previously, we showed that inhibition of the RANKL/RANK [receptor activator of nuclear factor kappa Β (NF-κB) ligand] pathway, by osteoprotegerin and the anti-osteoporotic drug denosumab, induces rodent and human ß cell proliferation. We demonstrate that the RANK pathway mediates cytokine-induced rodent and human ß cell death through RANK-TRAF6 interaction and induction of NF-κB activation. Osteoprotegerin and denosumab protected ß cells against this cytotoxicity. In human immune cells, osteoprotegerin and denosumab reduce proinflammatory cytokines in activated T-cells by inhibiting RANKL-induced activation of monocytes. In vivo, osteoprotegerin reversed recent-onset T1D in nonobese diabetic/Ltj mice, reduced insulitis, improved glucose homeostasis, and increased plasma insulin, ß cell proliferation, and mass in these mice. Serum from T1D subjects induced human ß cell death and dysfunction, but not α cell death. Osteoprotegerin and denosumab reduced T1D serum-induced ß cell cytotoxicity and dysfunction. Inhibiting RANKL/RANK could have therapeutic potential.

A Novel Algorithm for the Management of Inpatient COVID-19 Glucocorticoid-Induced Hyperglycemia.

Hyperglycemia in hospitalized patients with coronavirus disease 2019 (COVID-19) is linked to increased morbidity and mortality. This article reports on a novel insulin titration protocol for the management of glucocorticoid-induced hyperglycemia in hospitalized patients with COVID-19. Sixty-five patients with COVID-19 and glucocorticoid-induced hyperglycemia admitted after the protocol implementation were matched 1:1 to patients admitted before the treatment protocol rollout for analysis. In a large, diverse health system, the protocol achieved reductions in hypoglycemic events without increasing hyperglycemia or insulin use.

Coverage for Continuous Glucose Monitoring for Individuals with Type 2 Diabetes Treated with Nonintensive Therapies: An Evidence-Based Approach to Policymaking.

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance coverage is limited or nonexistent. This narrative review reports key findings from recent randomized, observational, and retrospective studies investigating use of CGM in T2D individuals treated with basal insulin only and/or noninsulin therapies and presents an evidence-based rationale for expanding access to CGM within this population.

Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets.

Glucose concentrations within target, appropriate gestational weight gain, adequate lifestyle, and, if necessary, antihypertensive treatment and low-dose aspirin reduces the risk of pre-eclampsia, preterm delivery, and other adverse pregnancy and neonatal outcomes in pregnancies complicated by type 1 diabetes. Despite the increasing use of diabetes technology (ie, continuous glucose monitoring and insulin pumps), the target of more than 70% time in range in pregnancy (TIRp 3·5-7·8 mmol/L) is often reached only in the final weeks of pregnancy, which is too late for beneficial effects on pregnancy outcomes. Hybrid closed-loop (HCL) insulin delivery systems are emerging as promising treatment options in pregnancy. In this Review, we discuss the latest evidence on pre-pregnancy care, management of diabetes-related complications, lifestyle recommendations, gestational weight gain, antihypertensive treatment, aspirin prophylaxis, and the use of novel technologies for achieving and maintaining glycaemic targets during pregnancy in women with type 1 diabetes. In addition, the importance of effective clinical and psychosocial support for pregnant women with type 1 diabetes is also highlighted. We also discuss the contemporary studies examining HCL systems in type 1 diabetes during pregnancies.

At-Home Use of a Pregnancy-Specific Zone-MPC Closed-Loop System for Pregnancies Complicated by Type 1 Diabetes: A Single-Arm, Observational Multicenter Study.

OBJECTIVE: There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the U.S. This study aimed to evaluate the feasibility and performance of at-home use of a zone model predictive controller-based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P). RESEARCH DESIGN AND METHODS: Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and 2 days of supervised training, participants used CLC-P targeting 80-110 mg/dL during the day and 80-100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63-140 mg/dL versus run-in. RESULTS: Ten participants (HbA1c 5.8 ± 0.6%) used the system from mean gestational age of 23.7 ± 3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 h per day, compared with run-in (run-in 64.5 ± 16.3% versus CLC-P 78.6 ± 9.2%; P = 0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P = 0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P = 0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use. CONCLUSIONS: The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are needed to further evaluate system efficacy and pregnancy outcomes.

Cost-effectiveness of the tubeless automated insulin delivery system vs standard of care in the management of type 1 diabetes in the United States.

BACKGROUND: A tubeless, on-body automated insulin delivery (AID) system (Omnipod 5 Automated Insulin Delivery System) demonstrated improved glycated hemoglobin A1c levels and increased time in range (70 mg/dL to 180 mg/dL) for both adults and children with type 1 diabetes in a 13-week multicenter, single-arm study. OBJECTIVE: To assess the cost-effectiveness of the tubeless AID system compared with standard of care (SoC) in the management of type 1 diabetes (T1D) in the United States. METHODS: Cost-effectiveness analyses were conducted from a US payer's perspective, using the IQVIA Core Diabetes Model (version 9.5), with a time horizon of 60 years and an annual discount of 3.0% on both costs and effects. Simulated patients received either tubeless AID or SoC, the latter being defined as either continuous subcutaneous insulin infusion (86% of patients) or multiple daily injections. Two cohorts (children: <18 years; adults: ≥18 years) of patients with T1D and 2 thresholds for nonsevere hypoglycemia (nonsevere hypoglycemia event [NSHE] <54 mg/dL and <70 mg/dL) were considered. Baseline cohort characteristics and treatment effects of different risk factors for tubeless AID were sourced from the clinical trial. Utilities and cost of diabetes-related complications were obtained from published sources. Treatment costs were derived from US national database sources. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Treating children with T1D with tubeless AID, considering an NSHE threshold of less than 54 mg/dL, brings incremental life-years (1.375) and quality-adjusted life-years (QALYs) (1.521) at an incremental cost of $15,099 compared with SoC, resulting in an incremental cost-effectiveness ratio of $9,927 per QALY gained. Similar results were obtained for adults with T1D assuming an NSHE threshold of less than 54 mg/dL (incremental cost-effectiveness ratio = $10,310 per QALY gained). Furthermore, tubeless AID is a dominant treatment option for children and adults with T1D assuming an NSHE threshold of less than 70 mg/dL compared with SoC. The probabilistic sensitivity analyses results showed that compared with SoC, in both children and adults with T1D, tubeless AID was cost-effective in more than 90% of simulations, assuming a willingness-to-pay threshold of $100,000 per QALY gained. The key drivers of the model were the cost of ketoacidosis, duration of treatment effect, threshold of NSHE, and definition of severe hypoglycemia. CONCLUSIONS: The current analyses suggest that the tubeless AID system can be considered a cost-effective treatment compared with SoC in people with T1D from a US payer's perspective. DISCLOSURES: This research was funded by Insulet. Mr Hopley, Ms Boyd, and Mr Swift are full-time Insulet employees and own stock in Insulet Corporation. IQVIA, the employer of Ms Ramos and Dr Lamotte, received consulting fees for this work. Dr Biskupiak is receiving research support and consulting fees from Insulet. Dr Brixner has received consulting fees from Insulet. The University of Utah has received research funding from Insulet. Dr Levy is a consultant with Dexcom and Eli Lilly and has received grant/research support from Insulet, Tandem, Dexcom, and Abbott Diabetes. Dr Forlenza conducted research sponsored by Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. He has been speaker/consultant/advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly.

All Children Deserve to Be Safe, Mothers Too: Evidence and Rationale Supporting CGM Use in Gestational Diabetes Within the Medicaid Population.

Gestational diabetes mellitus (GDM) is a common metabolic disease of pregnancy that threatens the health of several million women and their offspring. The highest prevalence of GDM is seen in women of low socioeconomic status. Women with GDM are at increased risk of adverse maternal outcomes, including increased rates of Cesarean section delivery, preeclampsia, perineal tears, and postpartum hemorrhage. However, of even greater concern is the increased risk to the fetus and long-term health of the child due to elevated glycemia during pregnancy. Although the use of continuous glucose monitoring (CGM) has been shown to reduce the incidence of maternal and fetal complications in pregnant women with type 1 diabetes and type 2 diabetes, most state Medicaid programs do not cover CGM for women with GDM. This article reviews current statistics relevant to the incidence and costs of GDM among Medicaid beneficiaries, summarizes key findings from pregnancy studies using CGM, and presents a rationale for expanding and standardizing CGM coverage for GDM within state Medicaid populations.

Expert Guidance on Off-Label Use of Hybrid Closed-Loop Therapy in Pregnancies Complicated by Diabetes.

Automated insulin delivery (AID) systems have established benefits in terms of glycemic control, health outcomes, and quality of life and are strongly recommended for people with type 1 diabetes outside of pregnancy. While evidence for use of investigational AID systems during pregnancy is promising, data and guidance are still needed regarding use of commercially available systems during pregnancy. Unfortunately, none of the hybrid closed-loop (HCL) systems that are currently available in the United States have glucose targets that are as aggressive as pregnancy glycemic targets, none have a pregnancy-specific algorithm, and none are approved for use during pregnancy. As such, any use of these systems during pregnancy is considered off-label in the United States and would be "assisted" by provider/user techniques. Despite these limitations, many women conceive while using clinically available HCL systems and may be hesitant to cease use during pregnancy. Achievement of strict pregnancy glycemic targets can be difficult, and it is conceivable that selective off-label use of clinically available HCL systems in some women could lead to improved glycemia. We herein offer expert guidance based on clinical experience and available case reports on how to identify appropriate candidates for HCL therapy in pregnancy, how to counsel pregnant women with diabetes on the potential risks and benefits of HCL therapy during pregnancy, and how to manage commercially available systems off-label throughout gestation in an assisted HCL approach.

Automated Insulin Delivery Systems as a Treatment for Type 2 Diabetes Mellitus: A Review.

OBJECTIVE: Approximately 6.3% of the worldwide population has type 2 diabetes mellitus (T2DM), and the number of people requiring insulin is increasing. Automated insulin delivery (AID) systems integrate continuous subcutaneous insulin infusion and continuous glucose monitoring with a predictive control algorithm to provide more physiologic glycemic control. Personalized glycemic targets are recommended in T2DM owing to the heterogeneity of the disease. Based on the success of hybrid closed-loop systems in improving glycemic control and safety in type 1 diabetes mellitus, there has been further interest in the use of these systems in people with T2DM. METHODS: We performed a review of AID systems with a focus on the T2DM population. RESULTS: In 5 randomized controlled trials, AID systems improve time in range and reduce glycemic variability, without increasing insulin requirements or the risk of hypoglycemia. CONCLUSION: AID systems in T2DM are safe and effective in hospitalized and closely monitored settings. Home studies of longer duration are required to assess for long-term benefit and identify target populations of benefit.

How introduction of automated insulin delivery systems may influence psychosocial outcomes in adults with type 1 diabetes: Findings from the first investigation with the Omnipod® 5 System.

AIMS: To evaluate psychosocial outcomes for adults with type 1 diabetes (T1D) using the tubeless Omnipod® 5 Automated Insulin Delivery (AID) System. METHODS: A single-arm, multicenter (across the United States), prospective safety and efficacy study of the tubeless AID system included 115 adults with T1D. Participants aged 18-70 years completed questionnaires assessing psychosocial outcomes - diabetes distress (T1-DDS), hypoglycemic confidence (HCS), well-being (WHO-5), sleep quality (PSQI), insulin delivery satisfaction (IDSS), diabetes treatment satisfaction (DTSQ), and system usability (SUS) - before and after 3 months of AID use. Associations among participant characteristics, psychosocial measures and glycemic outcomes were evaluated using linear regression analyses. RESULTS: Adults using the tubeless AID system demonstrated improvements in diabetes-specific psychosocial measures, including diabetes distress, hypoglycemic confidence, insulin delivery satisfaction, diabetes treatment satisfaction, and system usability after 3 months (all P < 0.001). No changes in general well-being or sleep quality were observed. The psychosocial outcomes assessed were not consistently associated with baseline participant characteristics (i.e., age, sex, diabetes duration, glycemic outcomes including percent time in range 70-180 mg/dL, percent time below range < 70 mg/dL, hemoglobin A1c, or insulin regimen). CONCLUSIONS: Use of the Omnipod 5 AID system was associated with significant improvements in diabetes-related psychosocial outcomes for adults with T1D. CLINICAL TRIALS REGISTRATION NUMBER: NCT04196140.

Real-World Evidence Supporting Tandem Control-IQ Hybrid Closed-Loop Success in the Medicare and Medicaid Type 1 and Type 2 Diabetes Populations.

Background: The Tandem Control-IQ (CIQ) system has demonstrated significant glycemic improvements in large randomized controlled and real-world trials. Use of this system is lower in people with type 1 diabetes (T1D) government-sponsored insurance and those with type 2 diabetes (T2D). This analysis aimed to evaluate the performance of CIQ in these groups. Methods and Materials: A retrospective analysis of CIQ users was performed. Users age ≥6 years with a t:slim X2 Pump and >30 days of continuous glucose monitoring (CGM) data pre-CIQ and >30 days post-CIQ technology initiation were included. Results: A total of 4243 Medicare and 1332 Medicaid CIQ users were analyzed among whom 5075 had T1D and 500 had T2D. After starting CIQ, the Medicare beneficiaries group saw significant improvement in time in target range 70-180 mg/dL (TIR; 64% vs. 74%; P < 0.0001), glucose management index (GMI; 7.3% vs. 7.0%; P < 0.0001), and the percentage of users meeting American Diabetes Association (ADA) CGM Glucometrics Guidelines (12.8% vs. 26.3%; P < 0.0001). The Medicaid group also saw significant improvement in TIR (46% vs. 60%; P < 0.0001), GMI (7.9% vs. 7.5%; P < 0.0001), and percentage meeting ADA guidelines (5.7% vs. 13.4%; P < 0.0001). Patients with T2D and either insurance saw significant glycemic improvements. Conclusions: The CIQ system was effective in the Medicare and Medicaid groups in improving glycemic control. The T2D subgroup also demonstrated improved glycemic control with CIQ use. Glucometrics achieved in this analysis are comparable with those seen in previous randomized controlled clinical trials with the CIQ system.

Outpatient Randomized Crossover Comparison of Zone Model Predictive Control Automated Insulin Delivery with Weekly Data Driven Adaptation Versus Sensor-Augmented Pump: Results from the International Diabetes Closed-Loop Trial 4.

Background: Automated insulin delivery (AID) systems have proven effective in increasing time-in-range during both clinical trials and real-world use. Further improvements in outcomes for single-hormone (insulin only) AID may be limited by suboptimal insulin delivery settings. Methods: Adults (≥18 years of age) with type 1 diabetes were randomized to either sensor-augmented pump (SAP) (inclusive of predictive low-glucose suspend) or adaptive zone model predictive control AID for 13 weeks, then crossed over to the other arm. Each week, the AID insulin delivery settings were sequentially and automatically updated by an adaptation system running on the study phone. Primary outcome was sensor glucose time-in-range 70-180 mg/dL, with noninferiority in percent time below 54 mg/dL as a hierarchical outcome. Results: Thirty-five participants completed the trial (mean age 39 ± 16 years, HbA1c at enrollment 6.9% ± 1.0%). Mean time-in-range 70-180 mg/dL was 66% with SAP versus 69% with AID (mean adjusted difference +2% [95% confidence interval: -1% to +6%], P = 0.22). Median time <70 mg/dL improved from 3.0% with SAP to 1.6% with AID (-1.5% [-2.4% to -0.5%], P = 0.002). The adaptation system decreased initial basal rates by a median of 4% (-8%, 16%) and increased initial carbohydrate ratios by a median of 45% (32%, 59%) after 13 weeks. Conclusions: Automated adaptation of insulin delivery settings with AID use did not significantly improve time-in-range in this very well-controlled population. Additional study and further refinement of the adaptation system are needed, especially in populations with differing degrees of baseline glycemic control, who may show larger benefits from adaptation.