Background and Aims

We are developing a blood glucose control technology based on intravenous (IV) blood sampling and delivery of insulin. A wearable device photometrically measures glucose in IV blood samples and delivers insulin via the same IV path. This removes the time lag between the interstitial and blood compartments associated to subcutaneous technologies and ensures faster insulin action. In turn, this facilitates blood glucose control without prior meal or activity information.

As the performance of the automated glucose measurement is a critical component of automated insulin delivery (AID) systems, we evaluate the effect of measurement delay and error on the time-in-range and time-below-range for type 1 diabetes in-silico subjects.

Methods

Glucose profiles for in-silico type 1 diabetes subjects are simulated using the UVa/Padova T1DMS model (33 subjects) and the NudgeBG model (1000 subjects, including the effect of unmeasured sources of variation such as stress and exercise). The simulated time for each subject is two days, involving four unannounced meals/day (20-70 grams of carbohydrates/meal). The control interval is 15 minutes.

Time in the narrow glycemic range (70-140 mg/dl) and time below range (<70 mg/dl) are computed for measurement delays up to 20 minutes and measurement errors up to 35%.

Results

UVa/Padova T1DMS model:

NudgeBG model:

Conclusions

As the measurement delay increases, the time-in-range decreases. Because IV sampling eliminates the lag between venous and interstitial compartments, it reduces the overall delay, leading to higher performance. The time-in-range is less sensitive to the measurement error, but the high accuracy of the photometric method ensures lower hypoglycemia risks.

Background and Aims

This study assessed the long‐term cost‐effectiveness of the MiniMed^TM 780G system versus Multiple Daily Injections (MDI) with intermittently scanned continuous glucose monitoring (isCGM) in people with type 1 diabetes (T1D) in Austria.

Methods

The IQVIA‐CORE‐Diabetes‐Model was used to perform cost‐effectiveness analysis over simulated patient lifetime. Clinical data were derived from the MiniMed^TM 780G system pivotal clinical study^1,2, the isCGM prospective observational real-world cohort study (FUTURE)³, and the European severe hypoglycaemia event rates (SHE) study⁴. For the former, assumptions for HbA1c reduction, given an 8.0% (63.9 mmol/mol) level at baseline, were 0.8% with MiniMed^TM 780G system and 0% with isCGM. For the latter, assumptions requiring medical assistance for SH were 0 vs 0.25 per patient-year for the MiniMed^TM 780G system versus isCGM. Cost data, expressed in 2020 Euros, were obtained from published sources and represented Austrian reimbursement prices. Societal perspective was used.

Results

The MiniMed^TM 780G system was associated with a quality‐adjusted life‐year (QALY) gain of 2.09 but higher overall costs versus MDI+isCGM, leading to an incremental cost‐effectiveness ratio (ICER) of €24475 per QALY-gained. MiniMed^TM 780G system use resulted in a lower cumulative incidence of diabetes‐related complications. Higher acquisition costs were partially offset by reduced complications costs. Extensive sensitivity analysis on key drivers confirmed the robustness of results.

Conclusions

Compared to MDI±isCGM, MiniMed™ 780G therapy was associated with clinical benefits and QALY improvements in patients with T1D in Austria. At a willingness-to-pay threshold of €28000 per QALY-gained, the system likely represents a cost-effective treatment option.

Background and Aims

Insulin therapy should be individualized to reflect patients’ unique treatment goals. The Omnipod 5 System provides novel full on-body hybrid closed-loop (HCL) control with customizable glucose targets from 110-150mg/dL (6.1-8.3mmol/L). This analysis aimed to assess system performance at varying glucose targets during the 3-month pivotal study in adults and adolescents.

Methods

Participants aged 14-70y with T1D≥6 months and A1C<10% used the HCL system for 3 months at home after a 14-day run-in phase of their standard therapy (ST). Participants selected glucose targets from 110-150mg/dL (6.1-8.3mmol/L) in 10mg/dL (0.6mmol/L) increments in a daily profile with up to 8 segments. Primary safety and efficacy endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and sensor glucose percent time in target range (TIR) (70-180mg/dL, 3.9-10.0mmol/L) during HCL at each glucose target compared with ST.

Results

Participants (N=128) were aged (mean±SD) 37±14y with T1D duration 18±12y and baseline A1C 7.2±0.9% (range 5.2-9.8%). TIR improved during the HCL phase for most targets, with reductions in time below range (TBR <70 and <54mg/dL [<3.9 and <3.0mmol/L]) (Table). There were 2 episodes of SH (both following user-initiated boluses), and no episodes of DKA reported.

Conclusions

The Omnipod 5 System was safely used by a large cohort of adults and adolescents with T1D at glucose targets from 110-150mg/dL (6.1-8.3mmol/L). Optimal results were seen using 110mg/dL (6.1mmol/L) as target, with 75.6% TIR and minimal TBR. Most (92%) participants completing the pivotal study opted to continue using the system in an extension phase.

Omnipod 5 Study Group as an author.

Background and Aims

Insulin therapy should be individualized for patients’ unique treatment goals. The Omnipod 5 System provides novel full on-body hybrid closed-loop (HCL) control with customizable glucose targets from 110-150mg/dL (6.1-8.3mmol/L). This analysis aimed to assess system performance at varying glucose targets during the 3-month pivotal study in children.

Methods

Participants aged 6-13.9y with T1D≥6 months and A1C<10% used the HCL system for 3 months at home after a 14-day run-in phase of their standard therapy (ST). Participants (or caregivers) selected glucose targets from 110-150mg/dL (6.1-8.3mmol/L) in 10mg/dL (0.6mmol/L) increments which could vary by time of day. Primary safety and efficacy endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and sensor glucose percent time in target range (TIR) (70-180mg/dL, 3.9-10.0mmol/L) during HCL at each glucose target compared with ST.

Results

Participants (N=112) were aged (mean±SD) 10.3±2.2y with T1D duration 4.7±2.6y and baseline A1C 7.7±0.9% (range 5.8-10.3%). TIR improved during the HCL phase for most targets, while time below range (TBR <70 and <54mg/dL [<3.9 and <3.0mmol/L]) remained low (Table). There was 1 SH episode (delayed eating after pre-meal bolus) and 1 DKA episode (suspected failed pump site) reported.

Conclusions

The Omnipod 5 System was safely used by a large cohort of children with T1D at glucose targets from 110-150mg/dL (6.1-8.3mmol/L). Optimal results were seen using 110mg/dL (6.1mmol/L) as target, with 68.4% TIR and minimal TBR. Most (99%) participants completing the pivotal study opted to continue using the system in an extension phase.

Omnipod 5 Study Group as an author.

Background and Aims

There are a growing number of Do-It-Yourself Artificial Pancreas Systems in the UK. These systems are unregulated and unapproved: exploring the perceived benefits, concerns and expectations of people with diabetes prior to using DIY APS; specifically the perceived response of their healthcare teams and any potential safety concerns is important.

Methods

A healthcare professional (HCP) and DIY-APS community collaborativley designed survey was distributed to users during UK “build sessions”.

Results

Twenty-seven responses were received (100% return) from two “build sessions”. Over half (59.3%,16/27) were female, mean age 35.7years (18.5%, 5/27), median diabetes duration 23 years (IQR 11.3-30.0) and median duration of pump therapy 60months (IQR 30-109). Almost all (25/27) pumps were NHS-funded. Half (51.9%, 14/27) were using FreeStyle Libre (FSL) +MiaoMiao, only 2 FSL were not NHS-funded. Important driving factors were “reduced time spent thinking about diabetes” (81.5%,22/27); improved glycaemic control (63%, 17/27) and reducing future complications (63%, 17/27). On a 7-point Likert (1=Very concerned), 5/27 (18.5%) users were at least somewhat (<4) concerned about both a negative HCP response or decreased NHS support. Concerns around safety (2/27, 7.4%) or lack of regulation (1/17, 3.7%) were less common. Even so, 74% (20/27) had informed their HCPs that they were planning to start DIY APS, one of which was perceived as unsupportive.

Conclusions

Perceived potential benefits outweigh regulatory or safety concerns. Users have concerns about the impact on their relationships with HCPs. This survey provides novel insights into user expectations prior to commencing DIY-APS and highlights the ongoing ethical challenges for users and HCPs alike.

Background and Aims

This study assessed the long‐term cost‐effectiveness of the MiniMed^TM 670G system versus Multiple Daily Injections (MDI) with intermittently scanned continuous glucose monitoring (isCGM) in people with type 1 diabetes (T1D) and baseline HbA1c < 8% in the Netherlands.

Methods

The IQVIA‐CORE‐Diabetes‐Model was used to perform cost‐effectiveness analysis over patient lifetime. Clinical data were derived from the retrospective Akturk study¹ and the prospective observational real-world cohort study (FUTURE)². MiniMed^TM 670G system use was associated with a reduction in HbA1c of 0.4%, from 7.8% (61.7 mmol/mol) at baseline to 7.4% (57.4 mmol/mol) at the end of the study¹; isCGM use was associated with a reduction in HbA1c of 0%². Severe hypoglycemic events requiring medical assistance were 0 vs 0.639 per patient-year for the MiniMed^TM 670G system versus the MDI+isCGM system, respectively. Cost data, expressed in 2020 Euros, were obtained from published sources and Dutch reimbursement prices. Societal perspective was used.

Results

The MiniMed^TM 670G system was associated with a quality‐adjusted life‐year (QALY) gain of 2.23 with higher overall costs versus MDI+isCGM, leading to an incremental cost‐effectiveness ratio of €6133 per QALY-gained. MiniMed^TM 670G system use resulted in a lower cumulative incidence of diabetes‐related complications. Higher acquisition costs were partially offset by reduced complications costs. Extensive sensitivity analysis on key drivers confirmed the robustness and the transferability of the results to future developments of the system.

Conclusions

At a willingness-to-pay threshold of €80000 per QALY-gained, the MiniMed™ 670G system likely represents a cost-effective option in people with T1D in the Netherlands.

Background and Aims

Open-source artificial pancreas systems (openAPS) autonomously adapt insulin delivery in order to achieve and maintain euglycemia. OpenAPS has not been approved for human use. We compared suggested adaptions and delivery of basal-rate doses of an openAPS with actual adaptions and delivery of the Medtronic 670G closed loop system (M670G). Both systems were simultaneously active.

Methods

Seven participants using M670G completed the study. Each participant carried a separated openAPS in close distance, which was filled with saline for a maximum duraton of seven days. Both systems simultaneously received independent CGM glucose measurements (Guardian Sensor 3 for M670G and Dexcom G6 glucose sensor for openAPS).

Results

OpenAPS and M670G were simultaneously active for 546.7 hours. CGM measurements matched in 92.59%. Decision to increase or decrease current basal-rate doses were consistent in 83.87% of all time-points among both systems. OpenAPS delivered higher basal rate doses compared to M670G during daytime (from 06:00 to 23:59h; 25.31 ± 16.71 IU vs. 14.70 ± 10.92 IU; p=0.033), nighttime (from 24:00 to 5:59h; 12.08 ± 4.95 IU vs. 6.82 ± 4.51 IU; p<0.001), euglycemia (CGM-glucose 4.0-10.0 mmol/L; 29.50 ± 20.95 IU vs. 15.94± 11.49 IU; p<0.001), and hyperglycemia (CGM-glucose >10.0 mmol/L; 3.51 ± 4.26 IU vs. 1.45± 1.71 IU; p=0.002) but similar doses during hypoglycemia (CGM-glucose <4.0 mmol/L; 0.32 ± 0.41 IU vs. 0.03 ± 0.06 IU; p=0.077).

Conclusions

Decision to increase or decrease current basal rate doses were similar in openAPS and M670G. In general, openAPS delivered higher basal rate doses as compared to M670G, except during hypoglycemia.

Background and Aims

Rather than utilizing user-entered settings, prediction-based commercial automated insulin delivery (AID) systems calculate internal representations of basal, carbohydrate-to-insulin (CIR) ratio and/or insulin sensitivity factor (ISF) to generate estimates of future glucose. Frequently simple formulas are used that incorporate a proportionality constant and total daily dose (TDD), total daily basal or weight. In contrast, the open-source AID system Loop relies on the settings provided by users and healthcare providers. We attempt to optimize the formulas used for basal, CIR and ISF based on data from Loop users.

Methods

Utilizing data from the Loop observational study we define an “aspirational” cohort of individuals who provide complete data (³90% CGM availability), meeting the standard international consensus on Time in Range clinical targets, no time below 40mg/dL and normal BMI. We then perform fitting to the traditional equation forms utilizing TDD and test additional forms that also include age, BMI and average daily carbohydrate consumption to optimize fitting.

Results

219/743 (29%) of Loop observational study participants who had settings data met inclusion criteria for the “aspirational” cohort. When fitted to TDD alone, basal and CIR tended to be more aggressive while ISF tended to be less aggressive than the standard equations. Incorporating BMI, daily carbohydrate consumption and total daily dose provided a significantly better fit than did formulas using TDD alone.

Conclusions

The data provided in the Loop observational study allows the creation of new formulas for basal, CIR and ISF that can benefit all users of prediction-based AID.

Background and Aims

As a technology-focused diabetes care center, we developed a virtual training program for patients with type 1 diabetes (T1D) who were upgrading to the hybrid closed-loop (HCL) system after mandatory isolation during the COVID-19 pandemic. We aim to describe outcomes of a virtual training program and compare the manual mode against the auto mode feature.

Methods

A prospective observational cohort study. Patients with diagnosis of T1D previously treated with multiple doses of insulin (MDI) or sensor augmented pump therapy (SAP) who were updating to Hybrid Close loop (HCL) system from March to July 2020, were included. The education program consisted in at least seven sessions according to baseline therapy. Virtual training and follow-up were done through the Zoom video conferencing application and Medtronic Carelink System version 3.1 software. Demographical, clinical and A1c data were collected. CGM data such as TIR, time below range (TBR), time above range (TAR) and coefficient of variation (%CV) after two weeks using manual mode and the last two weeks in auto mode were analyzed.

Results

91 patients were included in the analysis. Mean TIR achieved with manual mode was 77.3 ±11.3%. A significant increase in TIR to 81.6% ± 7.6% (p <0.001) was described after two weeks of auto mode use with a significant reduction in TBR<70mg/dL from 2,7%±2,28% to 1,83%±1,67% (p<0,001). Reduction of glycemic variability was significant independent of baseline therapy.

Conclusions

Virtual Training and follow-up through the Carelink platform allows the achievement of adequate results similar to face-to-face training.

Background and Aims

Outcome of type 1 diabetes (T1D) can only be improved by further automation of insulin delivery. As part of a real-life technical evaluation of a new advanced hybrid closed-loop system, and in the middle of COVID-19 pandemic, we analyzed outcomes after 5 weeks of use.

Methods

Thirty-five T1D patients, who were already using a Medtronic Minimed (MM)670G hybrid closed-loop in Auto Mode for >3 months, were invited for real-life evaluation of the MM780G advanced hybrid closed-loop system. Due to Covid-19, education and change between systems were largely done by remote video sessions. We used CareLink-generated reports to compare the last week of 670G system use with the 5th week of 780G system use.

Results

Patients successfully completed education and switched to SmartGuard (auto mode) after 48 hours. Average age 22±13 years (range: 7-49y), duration T1D 12±11y (range 0.7-49y), HbA1c 6.8±0.4% (51 mmol/mol). Time In Range during last week of 670G was 76±8% and improved to 84±6% with 780G use. Time Below Range was similar (2.6%). Time Above Range decreased from 21% on 670G to 13% on 780G. Average glucose improved from 9.2±1.4 mmol/l to 7.9±0.9 mmol/l for 780G use. Patients were in automatic modes (Auto Mode/SmartGuard) for 74% (670G) and 96% (780G) of the time.

Conclusions

It is very feasible to switch from a MM670G to an MM780G system in remote education sessions under COVID-19 circumstances. A strong improvement of important glucometric data was seen in a relatively short timeframe, even in a selected group of patients with good baseline diabetes regulation.