Early Real-World Performance of the MiniMed™ 780G Advanced Hybrid Closed-Loop System and Recommended Settings Use in the United States.

Background: The MiniMed™ 780G system (MM780G) with Guardian™ 4 sensor includes a 100 mg/dL glucose target (GT) and automated insulin corrections up to every 5 min and was recently approved for use in the United States. In the present study, early real-world MM780G performance and the use of recommended system settings (100 mg/dL GT with an active insulin time of 2 h), by individuals with type 1 diabetes, were evaluated. Methods: CareLink™ personal data uploaded between the launch of the MM780G to August 22, 2023 were aggregated and underwent retrospective analysis (based on user consent) and if users had ≥10 days of continuous glucose monitoring (CGM) data. The 24-h day CGM metrics, including mean glucose, percentage of time spent in (%TIR), above (%TAR), and below (%TBR) target range (70-180 mg/dL), in addition to delivered insulin and closed-loop (CL) exits, were compared between an overall group (n = 7499) and individuals who used recommended settings (each, for >95% of the time). An analysis of the same metrics for MiniMed™ 770G system (MM770G) users (n = 3851) who upgraded to the MM780G was also conducted (paired t-test or Wilcoxon signed-rank test, P < 0.05 considered statistically significant). Results: For MM780G users, CGM use, and time in CL were >90% and all MM780G CGM metrics exceeded consensus-recommended goals. With recommended settings (22% of all users), mean %TIR and %TITR (70-140 mg/dL) were 81.4% and 56.4%, respectively. For individuals who upgraded from the MM770G, %TIR and %TITR increased from 73.2% to 78.3% and 45.8% to 52.6%, respectively, while %TAR reduced from 25.1% to 20.2% (P < 0.001, for all three). CL exits/week averaged <1, for all MM780G users. Conclusions: Early real-world MM780G use in the United States demonstrated a high percentage of time in range with low time above and below range. These outcomes are similar to those observed for real-world MM780G use in other countries.

A Peek Under the Hood: Explaining the MiniMed™ 780G Algorithm with Meal Detection Technology.

The MiniMed™ 780G system (780G) received Conformité Européenne mark in June 2020 and was, recently, approved by the U.S. Food and Drug Administration (April 2023). Clinical trials and real-world analyses have demonstrated MiniMed™ 780G system safety and effectiveness and that glycemic outcomes (i.e., time in range) improve with recommended settings use. In this publication, we will explain the iterative development of the 780G algorithm and how this technology has simplified diabetes management.

Safety and Glycemic Outcomes During the MiniMedTM Advanced Hybrid Closed-Loop System Pivotal Trial in Children and Adolescents with Type 1 Diabetes.

Background: During MiniMed™ advanced hybrid closed-loop (AHCL) use by adolescents and adults in the pivotal trial, glycated hemoglobin (A1C) was significantly reduced, time spent in range (TIR) was significantly increased, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA). The present study investigated the same primary safety and effectiveness endpoints during AHCL use by a younger cohort with type 1 diabetes (T1D). Methods: An intention-to-treat population (N = 160, aged 7-17 years) with T1D was enrolled in a single-arm study at 13 investigational centers. There was a run-in period (∼25 days) using HCL or sensor-augmented pump with/without predictive low-glucose management, followed by a 3-month study period with AHCL activated at two glucose targets (GTs; 100 and 120 mg/dL) for ∼45 days each. The mean ± standard deviation values of A1C, TIR, mean sensor glucose (SG), coefficient of variation (CV) of SG, time at SG ranges, and insulin delivered between run-in and study were analyzed (Wilcoxon signed-rank test or t-test). Results: Compared with baseline, AHCL use was associated with reduced A1C from 7.9 ± 0.9% (N = 160) to 7.4 ± 0.7% (N = 136) (P < 0.001) and overall TIR increased from the run-in 59.4 ± 11.8% to 70.3 ± 6.5% by end of study (P < 0.001), without change in CV, time spent below range (TBR) <70 mg/dL, or TBR <54 mg/dL. Relative to longer active insulin time (AIT) settings (N = 52), an AIT of 2 h (N = 19) with the 100 mg/dL GT increased mean TIR to 73.4%, reduced TBR <70 mg/dL from 3.5% to 2.2%, and reduced time spent above range (TAR) >180 mg/dL from 28.7% to 24.4%. During AHCL use, there was no severe hypoglycemia or DKA. Conclusions: In children and adolescents with T1D, MiniMed AHCL system use was safe, A1C was lower, and TIR was increased. The lowest GT and shortest AIT were associated with the highest TIR and lowest TBR and TAR, all of which met consensus-recommended glycemic targets. ClinicalTrials.gov ID: NCT03959423.

Glycemic Outcomes During Early Use of the MiniMed™ 780G Advanced Hybrid Closed-Loop System with Guardian™ 4 Sensor.

Background: Safety and significant improvement in overall glycated hemoglobin (A1C) and percentage of time spent in (TIR), below (TBR), and above (TAR) glucose range were demonstrated in the pivotal trial of adolescents and adults using the MiniMed™ advanced hybrid closed-loop (AHCL) system with the adjunctive, calibration-required Guardian™ Sensor 3. The present study evaluated early outcomes of continued access study (CAS) participants who transitioned from the pivotal trial investigational system to the approved MiniMed™ 780G system with the non-adjunctive, calibration-free Guardian™ 4 Sensor (MM780G+G4S). Study data were presented alongside those of real-world MM780G+G4S users from Europe, the Middle East, and Africa. Methods: The CAS participants (N = 109, aged 7-17 years and N = 67, aged >17 years) used the MM780G+G4S for 3 months and data of real-world MM780G+G4S system users (N = 10,204 aged ≤15 years and N = 26,099 aged >15 years) were uploaded from September 22, 2021 to December 02, 2022. At least 10 days of real-world continuous glucose monitoring (CGM) data were required for analyses. Glycemic metrics, delivered insulin and system use/interactions underwent descriptive analyses. Results: Time in AHCL and CGM use were >90% for all groups. AHCL exits averaged 0.1/day and there were few blood glucose measurements (BGMs) (0.8/day-1.0/day). Adults in both cohorts met most consensus recommendations for glycemic targets. Pediatric groups met recommendations for %TIR and %TBR, although not those for mean glucose variability and %TAR, possibly due to low use of recommended glucose target (100 mg/dL) and active insulin time (2 h) settings (28.4% in the CAS cohort and 9.4% in the real-world cohort). The CAS pediatric and adult A1C were 7.2% ± 0.7% and 6.8% ± 0.7%, respectively, and there were no serious adverse events. Conclusions: Early clinical use of the MM780G+G4S was safe and involved minimal BGMs and AHCL exits. Consistent with real-world pediatric and adult use, outcomes were associated with achievement of recommended glycemic targets. Clinical Trial Registration number: NCT03959423.

Insulin pump therapy with and without continuous glucose monitoring in pregnant women with type 1 diabetes: a prospective observational Orchestra Foundation study in Poland.

AIMS: The effects of continuous subcutaneous insulin infusion (CSII) therapy with or without continuous glucose monitoring (CGM) on neonatal outcomes and glycemic outcomes of pregnant women with type 1 diabetes (T1D), living in Poland, were assessed. METHODS: This prospective observational study enrolled women with T1D (N = 481, aged 18-45 years) who were pregnant or planned pregnancy. All used CSII therapy and a subset used CGM with CSII (CSII + CGM). Neonatal outcomes (e.g., rate of large for gestational age [LGA] delivery [birth weight > 90th percentile]) and maternal glycemia (e.g., HbA1c and percentage of time at sensor glucose ranges) were evaluated. RESULTS: Overall HbA1c at trimesters 1, 2, and 3 was 6.8 ± 1.1% (50.9 ± 12.3 mmol/mol, N = 354), 5.8 ± 0.7% (40.1 ± 8.0 mmol/mol, N = 318), and 5.9 ± 0.7% (41.4 ± 8.0 mmol/mol, N = 255), respectively. A HbA1c target of < 6.0% (42 mmol/mol) at each trimester was achieved by 20.9% (74/354), 65.1% (207/318), and 58.0% (148/255), respectively. For women using CSII + CGM versus CSII only, HbA1c levels at trimesters 1, 2, and 3 were 6.5 ± 0.9% versus 7.1 ± 1.3% (47.8 ± 9.7 mmol/mol versus 54.3 ± 14.0 mmol/mol, p < 0.0001), 5.7 ± 0.6% versus 6.0 ± 0.9% (38.9 ± 6.5 mmol/mol versus 41.6 ± 9.3 mmol/mol, p = 0.0122), and 5.8 ± 0.6% versus 6.1 ± 0.8% (40.3 ± 6.9 mmol/mol versus 42.9 ± 9.1 mmol/mol, p = 0.0117), respectively. For the overall, CSII only, and CSII + CGM groups, rates of LGA delivery were 22.7% (74/326), 24.6% (34/138), and 21.3% (40/188), respectively. CONCLUSIONS: Observational assessment of women with T1D using CSII therapy demonstrated low HbA1c throughout pregnancy and low rates of LGA. The addition of CGM to CSII therapy compared to CSII therapy alone was associated with some improved maternal glycemic and neonatal outcomes. GOV IDENTIFIER: NCT01779141 (January 2013).

Glycemic Outcomes During Real-World Hybrid Closed-Loop System Use by Individuals With Type 1 Diabetes in the United States.

BACKGROUND: Glycemic outcomes during real-world hybrid closed-loop (HCL) system use by individuals with type 1 diabetes, in the United States, were retrospectively analyzed. METHODS: Hybrid closed-loop system data voluntarily uploaded to Carelink™ personal software from March 2017 to November 2020 by individuals (aged ≥7 years) using the MiniMed™ 670G system and having ≥10 days of continuous glucose monitoring data after initiating Auto Mode were assessed. Glycemic outcomes including the mean glucose management indicator (GMI), sensor glucose (SG), percentage of time spent in (TIR), below (TBR), and above (TAR) target range (70-180 mg/dL) were analyzed. Outcomes were also analyzed in a subgroup of users per baseline GMI of <7% versus >8%. RESULTS: The overall cohort (N = 123 355 users, with a mean of 87.9% of time in Auto Mode) had a GMI of 7.0% ± 0.4%, TIR of 70.4% ± 11.2%, TBR <70 mg/dL of 2.2% ± 2.1% and TAR>180 mg/dL of 27.5% ± 11.6%, post-Auto Mode initiation. Compared with pre-Auto Mode initiation, users (N = 52 941, 88.6% of time in Auto Mode) had a GMI that decreased from 7.3% ± 0.6% to 7.1% ± 0.5% (P < .001), TIR that increased from 61.5% ± 15.1% to 68.1% ± 11.9% (P < .001), TAR>180 mg/dL that decreased from 36.3% ± 15.7% to 29.8% ± 12.2% (P < .001) and TBR<70 mg/dL that decreased from 2.11 ± 2.4 to 2.07% ± 2.25% (P = .002). While all metrics statistically improved for the baseline GMI >8.0% group, the baseline GMI <7.0% group had unchanged TIR (77.4% ± 7.4% to 77.5% ± 8.0%, P = .456) and TAR>180 mg/dL that increased (19.2 ± 6.7 to 19.6 ± 7.9%, p < 0.001). CONCLUSION: Real-world HCL system use in the U.S. demonstrated overall glycemic control that trended similarly with the system pivotal trial outcomes and previous real-world system use analyses.

Improved Glycemia with Hybrid Closed-Loop Versus Continuous Subcutaneous Insulin Infusion Therapy: Results from a Randomized Controlled Trial.

Objective: To evaluate safety and effectiveness of MiniMed™ 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.

Comparison of MiniMed 780G system performance in users aged younger and older than 15 years: Evidence from 12 870 real-world users.

AIM: To investigate real-world glycaemic outcomes and goals achieved by users of the MiniMed 780G advanced hybrid closed loop (AHCL) system aged younger and older than 15 years with type 1 diabetes (T1D). MATERIALS AND METHODS: Data uploaded by MiniMed 780G system users from 27 August 2020 to 22 July 2021 were aggregated and retrospectively analysed based on self-reported age (≤15 years and >15 years) for three cohorts: (a) post-AHCL initiation, (b) 6-month longitudinal post-AHCL initiation and (c) pre- versus post-AHCL initiation. Analyses included mean percentage of time spent in AHCL and at sensor glucose ranges, insulin delivered and the proportion of users achieving recommended glucose management indicator (GMI < 7.0%) and time in target range (TIR 70-180 mg/dl > 70%) goals. RESULTS: Users aged 15 years or younger (N = 3211) achieved a GMI of 6.8% ± 0.3% and TIR of 73.9% ± 8.7%, while spending 92.7% of time in AHCL. Users aged older than 15 years (N = 8874) achieved a GMI of 6.8% ± 0.4% and TIR of 76.5% ± 9.4% with 92.3% of time in AHCL. Time spent at less than 70 mg/dl was within the recommended target of less than 4% (3.2% and 2.3%, respectively). Similar outcomes were observed for each group (N = 790 and N = 1642, respectively) in the first month following AHCL initiation, and were sustained over the 6-month observation period. CONCLUSIONS: This real-world analysis shows that more than 75% of users with T1D aged 15 years or younger using the MiniMed 780G system achieved international consensus-recommended glycaemic control, mirroring the achievements of the population aged older than 15 years.

Evaluation of Extended Infusion Set Performance in Adults with Type 1 Diabetes: Infusion Set Survival Rate and Glycemic Outcomes from a Pivotal Trial.

Background: Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D). Methods: This single-arm, nonrandomized trial enrolled adults (18-80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined. Results: The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03-0.51) and 0.4% (95% CI: 0.16-1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2-79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001). Conclusions: This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D. Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694).

Safety and Glycemic Outcomes During the MiniMed™ Advanced Hybrid Closed-Loop System Pivotal Trial in Adolescents and Adults with Type 1 Diabetes.

Introduction: This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods: This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/- predictive low glucose management or Auto Basal was enabled for ∼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (∼90 days), with glucose target set to 100 or 120 mg/dL for ∼45 days, followed by the other target for ∼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired t-test. Results: Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test, n = 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM-6 AM). The 100 mg/dL target increased TIR to 75.4% (n = 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase. Conclusions: These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience. Clinical Trial Registration number: NCT03959423.

Real-world performance of the MiniMed™ 670G system in Europe.

AIM: To evaluate the real-world performance of the MiniMed 670G system in Europe, in individuals with diabetes. MATERIALS AND METHODS: Data uploaded from October 2018 to July 2020 by individuals living in Europe were aggregated and retrospectively analysed. The mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR) and above (TAR) glycaemic ranges, system use and insulin consumed in users with 10 or more days of sensor glucose data after initial Auto Mode start were determined. Another analysis based on suboptimally (GMI > 8.0%) and well-controlled (GMI < 7.0%) glycaemia pre-Auto Mode initiation was also performed. RESULTS: Users (N = 14 899) spent a mean of 81.4% of the time in Auto Mode and achieved a mean GMI of 7.0% ± 0.4%, TIR of 72.0% ± 9.7%, TBR less than 3.9 mmol/L of 2.4% ± 2.1% and TAR more than 10 mmol/L of 25.7% ± 10%, after initiating Auto Mode. When compared with pre-Auto Mode initiation, GMI was reduced by 0.3% ± 0.4% and TIR increased by 9.6% ± 9.9% (P < .0001 for both). Significantly improved glycaemic control was observed irrespective of pre-Auto Mode GMI levels of less than 7.0% or of more than 8.0%. While the total daily dose of insulin increased for both groups, a greater increase was observed in the latter, an increase primarily due to increased basal insulin delivery. By contrast, basal insulin decreased slightly in well-controlled users. CONCLUSIONS: Most MiniMed 670G system users in Europe achieved TIR more than 70% and GMI less than 7% while minimizing hypoglycaemia, in a real-world environment. These international consensus-met outcomes were enabled by automated insulin delivery meeting real-time insulin requirements adapted to each individual user.

The Effectiveness of Virtual Training on the MiniMed™ 670G System in People with Type 1 Diabetes During the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has challenged the ability to do face-to-face training on advanced diabetes management technologies. In the United States, Medtronic Diabetes shifted from occasional to 100% virtual training on all diabetes devices in mid-March 2020. We studied the outcomes of virtual training on the MiniMed™ 670 G hybrid closed-loop system in type 1 diabetes. Methods: From March 20, 2020, to April 22, 2020 (intra-COVID-19), virtual training on the MiniMed 670 G system was completed using Zoom with satisfaction captured through online post-training surveys. Training efficiency was measuring by the days between the date of product shipment and the date of the first and final trainings. Patient satisfaction with training on the MiniMed 670 G was determined by Net Promotor Score® (NPS®). Uploads from CareLink™ Personal and CareLink Professional and calls to the Medtronic 24-h technical support team requesting educational/software assistance and/or help with health care provider telehealth visits were recorded. Continuous glucose monitoring (CGM) results were measured using the CareLink Personal database. All results except for the Zoom satisfaction survey were compared with data from January 20, 2020, to February 22, 2020, (Pre-COVID-19) when training was performed in-person. Results: The CGM metrics were comparable between pre- and intra-COVID-19 training. The Zoom video conferencing application had 98% satisfaction. The NPS rose from 78 to 84. The time between the pump shipment and the first and last (automode) training was significantly reduced from 14 ± 7 days to 11 ± 5 days (P < 0.001) and from 19 ± 7 days to 15 ± 15 days (P < 0.01), respectively. There was a decrease in the calls for educational assistance to the technical support team but an increase in requests for login and software installation support. Conclusions: Virtual training of individuals with diabetes on the MiniMed 670 G system resulted in high satisfaction and short-term glycemic results comparable with in-person training.

In-Clinic Evaluation of the MiniMed 670G System "Suspend Before Low" Feature in Children with Type 1 Diabetes.

BACKGROUND: The Medtronic predictive low-glucose management (PLGM) algorithm automatically stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low-glucose value within the next 30 min, and resumes delivery after hypoglycemia recovery. The present study evaluated the PLGM algorithm performance of the MiniMed™ 670G system SmartGuard™ "suspend before low" feature in children aged 7-13 years with type 1 diabetes (T1D). METHOD: Participants (N = 105, mean ± standard deviation of 10.8 ± 1.8 years) underwent an overnight in-clinic evaluation of the "suspend before low" feature with a preset low limit of 65 mg/dL. After exercise, frequent sample testing (FST) was conducted every 5 min if values were <70 mg/dL; every 15 min if 70-80 mg/dL; and every 30 min if >80 mg/dL. First-day performance of the Guardian™ Sensor 3 glucose sensor and continuous glucose monitoring system was also evaluated. RESULTS: Activation of the "suspend before low" feature occurred in 79 of the 105 participants, 79.7% (63/79) did not result in SG falling below 65 mg/dL. Mean glucose at activation was 102 ± 19 mg/dL and the initial insulin suspension duration was 87.5 ± 32.7 min. Four hours after insulin resumption, mean reference glucose was 130 ± 42 mg/dL. Mean absolute relative difference between the FST reference glucose and SG values on the first day of sensor wear was 11.4%. For the 26 participants in whom the "suspend before low" feature did not activate, none involved a reference glucose value ≤65 mg/dL, suggesting that the PLGM algorithm performed as intended. CONCLUSION: In children aged 7-13 years with T1D, the "suspend before low" feature of the MiniMed 670G system demonstrated a hypoglycemia prevention rate of nearly 80% after exercise and did not involve rebound hyperglycemia. There were no events of severe hypoglycemia during the evaluation.

Retrospective Analysis of 3-Month Real-World Glucose Data After the MiniMed 670G System Commercial Launch.

Real-world data from the first 3141 patients who completed 3 months of SmartGuard™ Auto Mode-enabled MiniMed™ 670G system use during the MiniMed 670G System Commercial Launch are reported. CareLink™ system data uploaded by real-world patients in the Commercial Launch from March 17, 2017 to December 31, 2017 were deidentified and analyzed. Comparisons of overall and night (10:00 PM-07:00 AM) time spent below, within, and above target glucose range (TIR) (70-180 mg/dL) between the baseline Manual Mode and closed-loop Auto Mode periods were made. These were evaluated alongside data from the 124 patients (aged 14-75 years) who completed the 3-month MiniMed 670G system pivotal trial (NCT 2463097), from June 2, 2015 to March 7, 2016. Real-world patients used Auto Mode a median 80.8% of the time (19 h and 24 min of the day). The overall mean of time spent in TIR was 66.0% during baseline Manual Mode versus 73.3% during Auto Mode (P < 0.001); the mean percentage of sensor glucose values <70 mg/dL was 2.7% versus 2.1% (P < 0.001); and that >180 mg/dL was 31.4% versus 24.6% (P < 0.001). The nighttime and early morning (03:00 AM-06:00 AM) TIR during Auto Mode was greater than that during baseline Manual Mode (nighttime: 77.2% vs. 67.4% [P < 0.001], early morning: 70.9% vs. 84.6% [P < 0.001]). Similar differences between Manual Mode and Auto Mode TIR were observed across different age groups. A slight increase in total insulin delivered was also observed. Consistent with improved glycemic control demonstrated in the pivotal trial, analysis of CareLink system data from >3000 real-world patients who completed 3 months of Auto Mode-enabled MiniMed 670G system use demonstrated increased TIR and decreased time below and above TIR compared with baseline. These improved clinical outcomes were observed across a broad age range of patients with type 1 diabetes.

IMPROVED HBA1C, TOTAL DAILY INSULIN DOSE, AND TREATMENT SATISFACTION WITH INSULIN PUMP THERAPY COMPARED TO MULTIPLE DAILY INSULIN INJECTIONS IN PATIENTS WITH TYPE 2 DIABETES IRRESPECTIVE OF BASELINE C-PEPTIDE LEVELS.

OBJECTIVE: Fasting C-peptide levels are used to differentiate type 1 from type 2 diabetes (T2D), thereby determining eligibility for coverage of continuous subcutaneous insulin infusion (CSII) for patients with T2D. METHODS: A total of 168 patients (74 female/94 male, aged 55.5 ± 9.7 years) were randomized to CSII, and 163 patients (77 female/86 male, aged 56.4 ± 9.5 years) were randomized to multiple daily injections (MDI) of insulin and grouped by baseline C-peptide level: group A (≤183 pmol/L [≤0.55 ng/mL]); group B (>183 pmol/L [>0.55 ng/mL]). At 6 months, the MDI group crossed over to CSII. Within- and between-group comparisons were recorded at 6 and 12 months in the entire group and separately for those patients aged ≥65 years. RESULTS: CSII reduced hemoglobin A1c (A1c) equally in groups A ( P = .0006, P = .0022) and B ( P<.0001, P<.0001) at 6 and 12 months, respectively. There was an increase in weight in group A versus group B at 6 months but not 12 months ( P<.03). CSII therapy reduced total daily dose (TDD) of insulin and improved treatment satisfaction similarly in groups A and B. The results for patients aged ≥65 years displayed a similar trend as the entire group. CONCLUSION: A1c, TDD of insulin, and treatment satisfaction improved for T2D patients using CSII versus MDI therapy, irrespective of baseline C-peptide level. A subgroup of patients aged ≥65 years displayed a similar trend. These results support abandoning C-peptide as a criterion for reimbursing CSII therapy in patients with diabetes. ABBREVIATIONS: A1c = hemoglobin A1c; CMS = Centers for Medicare and Medicaid Services; CSII = continuous subcutaneous insulin infusion; DTSQ = Diabetes Treatment Satisfaction Questionnaire; MDI = multiple daily injections; RCT = randomized controlled trials; T1D = type 1 diabetes; T2D = type 2 diabetes; TDD = total daily dose.

The Effect of Prior Continuous Glucose Monitoring Use on Glycemic Outcomes in the Pivotal Trial of the MiniMed™ 670G Hybrid Closed-Loop System.

A 3-month pivotal trial using the MiniMed™ 670G hybrid closed-loop (HCL) system in adolescent and adult patients with type 1 diabetes (T1D), relative to a 2-week baseline run-in period, resulted in increased sensor glucose (SG) values in target range (71-180 mg/dL), reduced HbA1c levels, and no events of diabetic ketoacidosis or severe hypoglycemia ( Clinicaltrials.gov : NCT02463097). This brief report evaluated how prior continuous glucose monitoring (CGM) experience influenced glycemic outcomes, in the same pivotal trial. HbA1c levels and the percentage of SG values in low, high, and in-target ranges were analyzed from participants (n = 124) completing the Hybrid Closed-Loop Pivotal Trial in T1D. There were 78 individuals comprising the prior CGM group and 46 comprising the no prior CGM group. Compared to baseline, HbA1c was reduced from 7.4% ± 0.9% to 6.9% ± 0.7% for the prior CGM group and from 7.5% ± 0.9% to 6.8% ± 0.5% for the no prior CGM group. For those with prior CGM experience, the mean percentage of in-target SG values increased from 66.9% ± 12.5% to 72.6% ± 9.1%, and for those with no prior CGM experience it increased from 66.6% ± 11.7% to 71.5% ± 8.5%. Similar improvement in glucose values in the low and high ranges, relative to baseline, was observed for both groups. Resulting outcomes, from baseline to study end, did not differ between each group. These findings suggest that individuals without prior CGM experience, and those already using CGM, will benefit similarly with use of the FDA-approved MiniMed 670G HCL system therapy.

Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes.

BACKGROUND: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated. METHODS: Adolescents (n = 30, ages 14-21 years) and adults (n = 94, ages 22-75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase. RESULTS: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%-88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%-92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P < 0.001) and from 7.3% ± 0.9% to 6.8% ± 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71-180 mg/dL) sensor glucose (SG) values increased from 60.4% ± 10.9% to 67.2% ± 8.2% (P < 0.001) in adolescents and from 68.8% ± 11.9% to 73.8% ± 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT® blood glucose values was 67.4% ± 27.7% compared to SG values of 72.0% ± 11.6% for adolescents and 74.2% ± 17.5% compared to 76.9% ± 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort. CONCLUSIONS: HCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA1c, hyperglycemia and hypoglycemia, compared to baseline. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02463097.

Effectiveness of Automated Insulin Management Features of the MiniMed® 640G Sensor-Augmented Insulin Pump.

BACKGROUND: Automated insulin management features of the MiniMed® 640G sensor-augmented pump system include suspension in response to predicted low sensor glucose (SG) values ("suspend before low"), suspension in response to existing low SG values ("suspend on low"), and automatic restarting of basal insulin delivery upon SG recovery. The effectiveness of these features was evaluated using CareLink® software data. METHODS: Anonymized data from MiniMed 640G system users (n = 4818), MiniMed 530G system users (n = 39,219), and MiniMed Paradigm® Veo™ system users (n = 43,193) who voluntarily uploaded pump and sensor data were retrospectively analyzed. Comparisons were made between days in which system features were enabled at any time and those in which they were not. Comparisons were also made between pump suspension events for which insulin delivery was automatically or manually resumed and between glycemic parameters of users who switched from the MiniMed Paradigm Veo system to the MiniMed 640G system. RESULTS: Days in which the MiniMed 640G "suspend before low" feature was enabled had lower percentages of SG readings ≤70 mg/dL (3.9 mmol/L) or ≥240 mg/dL (13.3 mmol/L) than days when it was not enabled (P < 0.001 for each). Users who switched from the MiniMed Paradigm Veo system to the MiniMed 640G system had fewer excursions below ≤70 mg/dL (P < 0.001) and ≥240 mg/dL (P < 0.001). SG values following automatically resumed pump suspension events recovered more rapidly and had a more stabilized endpoint than following manually resumed events. CONCLUSIONS: Automated insulin management features of the MiniMed 640G system can reduce the frequency of both high and low SG values and help stabilize SG after resumption of insulin delivery.

Spinal p38 mitogen-activated protein kinase mediates allodynia induced by first-degree burn in the rat.

Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been implicated in the development and maintenance of pain states. In this study, we tested whether p38 MAPK is involved in the response to first-degree burn of the hind paw. This injury induces central sensitization leading to tactile allodynia and is mediated by activation of Ca(2+) permeable AMPA/kainate receptors through PKC and PKA. We demonstrate that p38 MAPK is rapidly and robustly activated in the superficial spinal dorsal horn after mild thermal injury to the hind paw. Activated p38 MAPK was localized primarily to microglia and to a lesser extent in oligodendrocytes and lamina II neurons. Astrocytes were not involved in the p38 MAPK response. Intrathecal pretreatment of pharmacological inhibitors of p38 MAPK (SB203580, SD-282) dose-dependently blocked development of tactile allodynia, a characteristic of the first-degree burn model. The effects of the inhibitors on tactile allodynia were lost when they were administered after injury. These studies identify p38 MAPK as a major mediator of tactile allodynia, most likely activated downstream of AMPA/kainate receptors.