INTRODUCTION:The present study assessed the impact of the disposable Simplera Sync™ sensor with the MiniMed™ 780G (MM780G) advanced hybrid closed-loop (AHCL) system on type 1 diabetes (T1D) glycemic metrics, insulin delivery, and safety. MATERIALS AND METHODS:Youths (aged 7-17 years) and adults (aged 18-80 years) with T1D were enrolled in this single-arm, nonrandomized study at 24 sites in the United States. Participants began with an ∼2-week run-in period where hybrid closed-loop (HCL; auto basal only) or open-loop insulin delivery was used, followed by an ∼3-month study period with AHCL activated. Glycemic outcomes and insulin delivery during the last 6-7 weeks of the study, when settings were optimized at investigator's discretion, were compared with the run-in. Glycemic outcomes with the use of recommended optimal settings (ROS, 100 mg/dL glucose target with a 2-h active insulin time) were explored. RESULTS:Time in automation was high (>93%) and mean time in range (TIR) increased from 54.4% ± 15.7% to 71.4% ± 9.9% (P < 0.001) in youths and from 66.5% ± 12.6% to 80.2% ± 8.1% (P < 0.001) in adults, primarily due to reduced time above range. Youths had a slight increase in time below range (TBR <70 mg/dL) from 1.6% ± 1.7% to 1.9% ± 1.4% (P < 0.001), while adults had no significant difference in TBR. For ROS users, TIR was 74.7% ± 9.3% in youths and 83.8% ± 7.4% in adults. Throughout the study ∼60% of total daily insulin dose was automated (auto basal and auto correction) in both cohorts. There were two cases of severe hypoglycemia and one episode of diabetic ketoacidosis (not related to the device). CONCLUSIONS:MM780G use with the Simplera Sync sensor is safe and demonstrated improved glycemic outcomes in both pediatric and adult participants with T1D, compared with the run-in period.
BACKGROUND:The standard of care for hypothyroidism treatment worldwide is daily oral levothyroxine (LT4) sodium. Limitations associated with daily oral administration highlight the need for alternative formulations to address challenges in maintaining euthyroidism. XP-8121 (LT4 sodium for subcutaneous [SC] administration) is a ready-to-use, liquid formulation of LT4 intended for once-weekly administration, offering an alternative hormone replacement approach by bypassing the gastrointestinal tract. This study assessed the safety, tolerability, and target dose conversion factor from oral LT4 to XP-8121 SC in adult participants. PARTICIPANTS AND METHODS:This Phase 2, multicenter, nonrandomized, open-label, single-arm, self-controlled study (NCT05823012) evaluated XP-8121 SC in 46 adults with hypothyroidism receiving a consistent dose of oral LT4 for at least 3 months prior to screening, with documented normal thyrotropin (TSH) levels at least 3 months prior to screening and normal free thyroxine (fT4) at screening. The weekly XP-8121 SC dose was initiated at 50% of the target dose and titrated every 2 weeks for up to 8 weeks based on individual response using fT4 trough concentrations. Following titration, participants continued the established dose during a 4-week maintenance period. RESULTS:Of the 46 participants enrolled, 39 completed the study. The majority were female (37; 80.4%) and identified as White (44; 95.7%). The final dose conversion factor point estimate ranged from 4.02 (90% confidence interval [CI]: 3.79-4.27) to 4.24 (90% CI: 4.06-4.42), supporting a conversion factor of approximately four times the daily oral LT4 dose when transitioning to XP-8121 SC. Although participants were initially underdosed during titration, TSH normalization was observed in 79.5% and fT4 normalization in 100% among those who completed the study on a consistent dose (unchanged for 6 weeks) at the end of maintenance. Overall, 78 treatment-emergent adverse events (TEAEs) were reported in 30 participants (65.2%) who received at least one dose of XP-8121 SC; fatigue (21.7%) and injection-site pain (10.9%) were the most common TEAEs. A majority of participants who completed the study reported higher satisfaction, convenience, and perceived effectiveness with once-weekly XP-8121 SC and expressed preference over daily oral LT4. CONCLUSIONS:Once-weekly XP-8121 SC was generally well-tolerated in all treated participants and supported a dose conversion factor of four times the daily oral LT4 dose.
OBJECTIVE:To characterize simplified meal bolus strategies in adults with insulin-treated type 2 diabetes using automated insulin delivery (AID). RESEARCH DESIGN AND METHODS:In the 2IQP study, a 13-week randomized, controlled trial comparing Control-IQ+ AID to continuation of pre-study insulin regimen with continuous glucose monitoring, 201 participants in the AID arm were classified by meal bolus strategy. Glycemic outcomes were compared to baseline. RESULTS:68 participants' meal bolus strategies (33.8%) were classified as Carbohydrate Counting, 79 (39.3%) were classified as Preset Carbohydrate Amounts, 27 (13.4%) were classified as Fixed Insulin Doses, and 27 (13.4%) as Other Methods. All bolus strategies were associated with similar, significant improvements in HbA1c from baseline: -0.9% for Carbohydrate Counting (P < 0.001), -1.1% for Preset Carbohydrate Amounts (P < 0.001), -0.8% for Fixed Insulin Doses (P < 0.001), and -0.9% for Other Methods (P = 0.003). Hypoglycemia rates were low at baseline and remained low for all bolus strategies. As participants gained experience with the Control-IQ+ AID system, more participants opted to use a simplified bolus strategy in the second half of the study compared with the first half (63% vs. 52%). CONCLUSION:Simplified bolus strategies worked well for adults with type 2 diabetes using Control-IQ+ in the 2IQP trial. All bolus strategies led to substantial HbA1c improvements, without safety concerns.
Objective: To evaluate the function and safety of the SteadiSet™ infusion set over a continuous 7-day wear period in adults with type 1 diabetes. Research Design and Methods: Participants used a SteadiSet infusion set with a t:slim X2™ insulin pump with Control-IQ™ technology, and either insulin aspart or insulin lispro, for a target of 7 days for 12 consecutive wear periods. Each set removed before 7 days was adjudicated by an independent committee to assess the cause of early removal and to determine whether criteria for primary or key secondary endpoints were met. Results: There were 260 participants who inserted 3028 infusion sets. For the primary endpoint, the Kaplan-Meier 7-day survival estimate was 95% (95% CI 94% to 96%). For the key secondary endpoint, which expanded the reasons for a failed infusion set, the Kaplan-Meier 7-day survival estimate was 84% (95% CI 82% to 86%). For both endpoints, the P value was <0.001 compared with a prespecified survival rate of 75%. Time-in-range 70-180 mg/dL (TIR) increased through day 3 of set wear and then decreased through day 7, with the average TIR being 70.6% over the entire wear period across all infusion sets, including those that failed. An increase in total daily insulin was observed from day 4 through day 7. Conclusions: The 7-day survival of the SteadiSet infusion set was very high for the primary endpoint and at an acceptable level with respect to early removal for any reason related to the device.
Objective: To evaluate safety and effectiveness of MiniMed (TM) 670G hybrid closed loop (HCL) in comparison with continuous subcutaneous insulin infusion (CSII) therapy for 6 months in persons with type 1 diabetes (T1D).Methods: Adults (aged 18-80 years), adolescents, and children (aged 2-17 years) with T1D who were using CSII therapy were enrolled and randomized (1:1) to 6 months of HCL intervention (n = 151, mean age of 39.9 +/- 19.8 years) or CSII without continuous glucose monitoring (n = 151, 35.7 +/- 18.4 years). Primary effectiveness endpoints included change in A1C for Group 1 (baseline A1C >8.0%), from baseline to the end of study, and difference in the end of study percentage of time spent below 70 mg/dL (%TBR <70 mg/dL) for Group 2 (baseline A1C <= 8.0%), to show superiority of HCL intervention versus control. Secondary effectiveness endpoints were change in A1C and %TBR <70 mg/dL for Group 2 and Group 1, respectively, to show noninferiority of HCL intervention versus control. Primary safety endpoints were rates of severe hypoglycemia and diabetic ketoacidosis (DKA).Results: Change in A1C and difference in %TBR <70 mg/dL for the overall group were significantly improved, in favor of HCL intervention. In addition, a significant mean (95% confidence interval) change in A1C was observed for both Group 1 (-0.8% [-1.1% to -0.4%], P < 0.0001) and Group 2 (-0.3% [-0.5% to -0.1%], P < 0.0001), in favor of HCL intervention. The same was observed for difference in %TBR <70 mg/dL for Group 1 (-2.2% [-3.6% to -0.9%]) and Group 2 (-4.9% [-6.3% to -3.6%]) (P < 0.0001 for both). There was one DKA event during run-in and six severe hypoglycemic events: two during run-in and four during study (HCL: n = 0 and CSII: n = 4 [6.08 per 100 patient-years]).Conclusions: This RCT demonstrates that the MiniMed 670G HCL safely and significantly improved A1C and %TBR <70 mg/dL compared with CSII control in persons with T1D, irrespective of baseline A1C level.
