The Health Economics of Automated Insulin Delivery Systems and the Potential Use of Time in Range in Diabetes Modeling: A Narrative Review.

Intensive therapy with exogenous insulin is the treatment of choice for individuals living with type 1 diabetes (T1D) and some with type 2 diabetes, alongside regular glucose monitoring. The development of systems allowing (semi-)automated insulin delivery (AID), by connecting glucose sensors with insulin pumps and algorithms, has revolutionized insulin therapy. Indeed, AID systems have demonstrated a proven impact on overall glucose control, as indicated by effects on glycated hemoglobin (HbA1c), risk of severe hypoglycemia, and quality of life measures. An alternative endpoint for glucose control that has arisen from the use of sensor-based continuous glucose monitoring is the time in range (TIR) measure, which offers an indication of overall glucose control, while adding information on the quality of control with regard to blood glucose level stability. A review of literature on the health-economic value of AID systems was conducted, with a focus placed on the growing place of TIR as an endpoint in studies involving AID systems. Results showed that the majority of economic evaluations of AID systems focused on individuals with T1D and found AID systems to be cost-effective. Most studies incorporated HbA1c, rather than TIR, as a clinical endpoint to determine treatment effects on glucose control and subsequent quality-adjusted life year (QALY) gains. Likely reasons for the choice of HbA1c as the chosen endpoint is the use of this metric in most validated and established economic models, as well as the limited publicly available evidence on appropriate methodologies for TIR data incorporation within conventional economic evaluations. Future studies could include the novel TIR metric in health-economic evaluations as an additional measure of treatment effects and subsequent QALY gains, to facilitate a holistic representation of the impact of AID systems on glycemic control. This would provide decision makers with robust evidence to inform future recommendations for health care interventions.

A European Cost-Utility Analysis of the MiniMed™ 780G Advanced Hybrid Closed-Loop System Versus Intermittently Scanned Continuous Glucose Monitoring with Multiple Daily Insulin Injections in People Living with Type 1 Diabetes.

Background: Advanced hybrid closed-loop (AHCL) automated insulin delivery systems are the most effective therapy in terms of assisting people with type 1 diabetes (T1D) to achieve glycemic targets; however, the cost can represent a barrier to uptake. In this study, a cost-utility analysis of the MiniMed™ 780G AHCL system (MM780G) versus intermittently scanned continuous glucose monitoring (is-CGM) plus multiple daily insulin injections (MDI) in people with T1D not achieving glycemic goals was performed across six European countries. Methods: Clinical input data were sourced from the ADAPT trial. Assuming a baseline HbA1c of 9.04%, HbA1c reductions of 1.54% for AHCL and 0.2% for is-CGM+MDI were modeled. The analyses were performed from a payer perspective over a time horizon of 40 years and an annual discount rate of 3% was applied. Results: Across all countries, the use of AHCL was projected to result in an incremental gain in quality-adjusted life expectancy of >2 quality-adjusted life years (QALYs) versus is-CGM+MDI. Lifetime direct costs were higher with AHCL resulting in incremental cost-utility ratios for AHCL versus is-CGM+MDI ranging from EUR 11,765 per QALY gained in Austria to EUR 43,963 per QALY gained in Italy. Conclusions: For people with T1D managed with is-CGM+MDI not achieving glycemic targets, initiation of the MM780G system was projected to improve long-term clinical outcomes; however, due to differences in health care costs between countries, the health economic outcomes differed. In all included countries, AHCL is likely to be cost-effective relative to is-CGM+MDI for people not achieving glycemic goals with is-CGM+MDI. The ADAPT trial is registered with ClinicalTrials.gov, NCT04235504.

Twelve-month results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closed-loop therapy outcomes versus conventional therapy in adults with type 1 diabetes.

AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy.

Advanced Hybrid Closed Loop in Adult Population With Type 1 Diabetes: A Substudy From the ADAPT Randomized Controlled Trial in Users of Real-Time Continuous Glucose Monitoring.

BACKGROUND: This analysis reports the findings from a predefined exploratory cohort (cohort B) from the ADAPT (ADvanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes) study. Adults with type 1 diabetes (T1D) with suboptimal glucose control were randomly allocated to an advanced hybrid closed-loop (AHCL) system or multiple daily injections of insulin (MDI) plus real-time continuous glucose monitoring (RT-CGM). METHODS: In this prospective, multicenter, exploratory, open-label, randomized controlled trial, 13 participants using MDI + RT-CGM and with HbA1c ≥8.0% were randomized to switch to AHCL (n = 8) or continue with MDI + RT-CGM (n = 5) for six months. Prespecified endpoints included the between-group difference in mean change from baseline in HbA1c, CGM-derived measures of glycemic control, and safety. RESULTS: The mean HbA1c level decreased by 1.70 percentage points in the AHCL group versus a 0.60 percentage point decrease in the MDI + RT-CGM group, with a model-based treatment effect of -1.08 percentage points (95% confidence interval [CI] = -2.17 to 0.00 percentage points; P = .0508) in favor of AHCL. The percentage of time spent with sensor glucose levels between 70 and 180 mg/dL in the study phase was 73.6% in the AHCL group and 46.4% in the MDI + RT-CGM group; model-based between-group difference of 28.8 percentage points (95% CI = 12.3 to 45.3 percentage points; P = .0035). No diabetic ketoacidosis or severe hypoglycemia occurred in either group. CONCLUSIONS: In people with T1D with HbA1c ≥8.0%, the use of AHCL resulted in improved glycemic control relative to MDI + RT-CGM. The scale of improvement suggests that AHCL should be considered as an option for people not achieving good glycemic control on MDI + RT-CGM.

Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study.

BACKGROUND: Adults with type 1 diabetes who are treated with multiple daily injections of insulin plus intermittently scanned continuous glucose monitoring (isCGM) can have suboptimal glucose control. We aimed to assess the efficacy of an advanced hybrid closed loop (AHCL) system compared with such therapy in this population. METHODS: The Advanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes (ADAPT) trial is a prospective, multicentre, open-label, randomised controlled trial that involved 14 centres in three European countries (France, Germany, and the UK). We enrolled patients who were at least 18 years of age, had a type 1 diabetes duration of at least 2 years, HbA1c of at least 8% (64 mmol/mol), and were using multiple daily injections of insulin plus isCGM (cohort A) or real time continuous glucose monitoring (cohort B) for at least 3 months. Here, only results for cohort A are reported. Participants were randomly allocated 1:1 to AHCL therapy or continuation of multiple daily injections of insulin plus continuous glucose monitoring for 6 months with an investigator-blinded block randomisation procedure. Participants and treating clinicians could not be masked to the arm assignment. The primary endpoint was the between-group difference in mean HbA1c change from baseline to 6 months in the intention-to-treat population using AHCL therapy and those using multiple daily injections of insulin plus isCGM. The primary endpoint was analysed using a repeated measures random-effects model with the study arm and period as factors. Safety endpoints included the number of device deficiencies, severe hypoglycaemic events, diabetic ketoacidosis, and serious adverse events. This study is registered with ClinicalTrials.gov, NCT04235504. FINDINGS: Between July 13, 2020, and March 12, 2021, 105 people were screened and 82 randomly assigned to treatment (41 in each arm). At 6 months, mean HbA1c had decreased by 1·54% (SD 0·73), from 9·00% to 7·32% in the AHCL group and 0·20% (0·80) in the multiple daily injections of insulin plus isCGM from 9·07% to 8·91% (model-based difference -1·42%, 95% CI -1·74 to -1·10; p<0·0001). No diabetic ketoacidosis, severe hypoglycaemia, or serious adverse events related to study devices occurred in either group; two severe hypoglycaemic events occurred in the run-in phase. 15 device-related non-serious adverse events occurred in the AHCL group, compared with three in the multiple daily injections of insulin plus isCGM group. Two serious adverse events occurred (one in each group), these were breast cancer (in one patient in the AHCL group) and intravitreous haemorrhage (in one patient in the multiple daily injections of insulin plus isCGM group). INTERPRETATION: In people with type 1 diabetes using multiple daily injections of insulin plus isCGM and with HbA1c of at least 8%, the use of AHCL confers benefits in terms of glycaemic control beyond those that can be achieved with multiple daily injections of insulin plus isCGM. These data support wider access to AHCL in people with type 1 diabetes not at target glucose levels. FUNDING: Medtronic International Trading Sàrl.

Cost-Effectiveness of Hybrid Closed Loop Insulin Pumps Versus Multiple Daily Injections Plus Intermittently Scanned Glucose Monitoring in People With Type 1 Diabetes in The Netherlands.

INTRODUCTION: Hybrid closed loop (HCL) insulin pump systems and intermittently scanned continuous glucose monitoring (IS-CGM) are increasingly used by individuals with type 1 diabetes (T1D). The aim of the analysis was to compare the long-term cost-effectiveness of the MiniMed 670G HCL system versus IS-CGM plus multiple daily injections of insulin (MDI) or continuous subcutaneous insulin infusion (CSII) in adults with T1D in the Netherlands. METHODS: The analysis was performed using the IQVIA CORE Diabetes Model with clinical input data sourced from observational studies. Simulated patients were assumed to have a baseline HbA1c of 7.8%. Use of the MiniMed 670G system was assumed to reduce HbA1c by 0.4% and confer a quality-of-life (QoL) benefit through reduced fear of hypoglycemia (FoH). The analysis was performed from a societal perspective over a lifetime time horizon; future costs and clinical outcomes pertaining to the Netherlands were used and discounted at 4% and 1.5% per annum, respectively. RESULTS: Use of the MiniMed 670G HCL system was projected to improve mean quality-adjusted life expectancy by 2.231 quality-adjusted life years (QALYs) versus IS-CGM. Total mean lifetime costs were EUR 13,683 higher with the MiniMed 670G system resulting in an ICER of EUR 6133 per QALY gained. Sensitivity analyses revealed findings to be sensitive to changes in assumptions around severe hypoglycemic event rates and the (QoL) benefit associated with reduced FoH. CONCLUSIONS: Over patient lifetimes, for adults with long-standing T1D in the Netherlands, use of the MiniMed 670G system is projected to be cost-effective versus IS-CGM plus MDI or CSII.

Randomised controlled trial of Advanced Hybrid Closed Loop in an Adult Population with Type 1 Diabetes (ADAPT): study protocol and rationale.

INTRODUCTION: For many people with type 1 diabetes who struggle to achieve glycaemic control with multiple daily injections of insulin (MDI) plus self-monitoring of blood glucose, MDI plus intermittently scanned continuous glucose monitoring (IS-CGM) or real-time continuous glucose monitoring (RT-CGM), or insulin administration using insulin pump therapy represent optimised care in many regions. Through technological advances an advanced hybrid closed loop (AHCL) system has been developed; studies of incremental effects relative to MDI plus IS-CGM are lacking. METHODS AND ANALYSIS: The Advanced Hybrid Closed Loop study in Adult Population with Type 1 Diabetes (ADAPT) study is a multinational, prospective, open-label, confirmatory and exploratory randomised controlled trial to examine outcomes with the MiniMed 670G version 4.0 AHCL system (with an equivalent algorithm and commercialised as the MiniMed 780G system, referred to as AHCL) relative to MDI plus IS-CGM in adults with baseline HbA1c≥8.0%. An exploratory cohort will compare AHCL with MDI plus RT-CGM. The study will be conducted in approximately 124 adults on MDI plus either IS-CGM or RT-CGM for at least 3 months prior to screening. The primary endpoint will be the difference in mean HbA1c change from baseline to 6 months between the AHCL and the MDI plus IS-CGM arms. Secondary endpoints will include proportion of time spent in hypoglycaemic, euglycaemic and hyperglycaemic ranges. ETHICS AND DISSEMINATION: The ADAPT study will be conducted in accordance with the requirements of the Declaration of Helsinki and local laws and regulations, and has been approved by ethics committees. The trial will provide valuable information on the incremental benefits that may be provided by AHCL for patients failing to achieve glycaemic targets on MDI plus IS-CGM or RT-CGM and form a basis for health economic evaluations to support market access. TRIAL REGISTRATION NUMBER: NCT04235504; Pre-results.

Cost-Effectiveness Analysis of an Advanced Hybrid Closed-Loop Insulin Delivery System in People with Type 1 Diabetes in Greece.

AbstractIntroduction: Usage of automated insulin delivery systems is increasing for the treatment of people with type 1 diabetes (T1D). This study compared long-term cost-effectiveness of the Advanced Hybrid Closed Loop MiniMed 780G (AHCL) system versus sensor augmented pump (SAP) system with predictive low glucose management (PLGM) or multiple daily injections (MDI) plus intermittently scanned continuous glucose monitoring (isCGM) in people with T1D in Greece. Methods: Analyses were performed using the IQVIA CORE Diabetes Model, with clinical input data sourced from various studies. In the AHCL versus SAP plus PLGM analysis, patients were assumed to have 7.5% baseline glycated hemoglobin (HbA1c), when comparing AHCL with MDI plus isCGM baseline HbA1c was assumed to be 7.8%. HbA1c was reduced to 7.0% following AHCL treatment initiation but remained at baseline levels in the comparator arms. Analyses were performed from a societal perspective over a lifetime time horizon. Future costs and clinical outcomes were discounted at 1.5% per annum. Results: AHCL was associated with increased quality-adjusted life expectancy of 0.284 quality-adjusted life years (QALYs) and EUR 10,173 lower mean total lifetime costs with SAP plus PLGM. Compared with MDI plus isCGM, AHCL was associated with increased quality-adjusted life expectancy of 2.708 QALYs, EUR 76,396 higher mean total lifetime costs, and an incremental cost-effectiveness ratio of EUR 29,869 per QALY. Extensive sensitivity analysis confirmed the robustness of results. Conclusions: Over patient lifetime, the MiniMed 780G system is likely to be cost saving compared with the SAP plus PLGM system and cost-effective compared with MDI plus isCGM in people with T1D in Greece.

Cost-effectiveness of a novel hybrid closed-loop system compared with continuous subcutaneous insulin infusion in people with type 1 diabetes in the UK.

AIMS: The MiniMed 670 G insulin pump system is the first commercially available hybrid closed-loop (HCL) insulin delivery system and clinical studies have shown that this device is associated with incremental benefits in glycemic control relative to continuous subcutaneous insulin infusion (CSII) with or without continuous glucose monitoring (CGM). The aim was to evaluate the long-term cost-effectiveness of the MiniMed 670 G system versus CSII alone in people with type 1 diabetes (T1D) in the UK. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using the IQVIA CORE Diabetes Model. Clinical input data were sourced from a clinical trial of the MiniMed 670 G system in 124 adults and adolescents with T1D. The analysis was performed over a lifetime time horizon and both future costs and clinical outcomes were discounted at 3.5% per annum. The analysis was performed from a healthcare payer perspective. RESULTS: The use of the MiniMed 670 G system led to an improvement in quality-adjusted life expectancy of 1.73 quality-adjusted life years (QALYs), relative to CSII. Total lifetime direct costs were GBP 35,425 higher with the MiniMed 670 G system than with CSII resulting in an incremental cost-effectiveness ratio (ICER) of GBP 20,421 per QALY gained. Sensitivity analyses revealed that the ICER was sensitive to assumptions around glycemic control and assumptions relating to the quality-of-life benefit associated with a reduction in fear of hypoglycemia. LIMITATIONS: Long-term projections from short-term data are inherently associated with uncertainty but represent arguably the best available evidence in lieu of long-term clinical trials. CONCLUSIONS: In the UK, over patient lifetimes, the incremental clinical benefits associated with the use of MiniMed 670 G system means that it is likely to be cost-effective relative to the continued use of CSII in people with T1D, particularly for those with a fear of hypoglycemia or poor baseline glycemic control.

Predicting Factors Associated with Hypoglycemia Reduction with Automated Predictive Insulin Suspension in Patients at High Risk of Severe Hypoglycemia: An Analysis from the SMILE Randomized Trial.

Background: This analysis from the SMILE randomized study was performed to identify predictive factors associated with the greatest reductions in hypoglycemia with the Medtronic MiniMed™ 640G Suspend before low feature in adults with type 1 diabetes at high risk of severe hypoglycemia. Methods: Clinical and treatment-related factors associated with decreased sensor hypoglycemia (SH) were identified in participants from the intervention arm by univariate and multivariate analyses. Results: The reduction in SH events <54 mg/dL (<3.0 mmol/L) in the intervention group was significantly (P < 0.0001) associated with the baseline mean number of sensor hypoglycemic events (MNSHE) <54 mg/dL. When excluding continuous glucose monitoring (CGM) factors not readily available (MNSHE, duration of SH events, area under the curve, mean amplitude of glycemic excursions), only the baseline mean time spent <54 mg/dL was found to be a significant independent predictor factor (P < 0.0001). Baseline HbA1c, mean self-monitoring of blood glucose (SMBG), and coefficient of variation of SMBG were significant, although weak, predictors in the absence of any CGM data. Conclusions: The greatest reductions in SH events achieved with the MiniMed 640G system with the Suspend before low feature were seen in participants with higher baseline MNSHE. Measuring these (usually uncollected) events can be a useful tool to predict hypoglycemia reduction. ClinicalTrials.gov Registration Identifier NCT02733991.

Cost-Effectiveness of Sensor-Augmented Insulin Pump Therapy Versus Continuous Insulin Infusion in Patients with Type 1 Diabetes in Turkey.

Background and Aims: Sensor-augmented pump therapy (SAP) combines continuous glucose monitoring with continuous subcutaneous insulin infusion (CSII). SAP is costlier than CSII but provides additional clinical benefits relative to CSII alone. A long-term cost-effectiveness analysis was performed to determine whether SAP is cost-effective relative to CSII in patients with type 1 diabetes (T1D) in Turkey. Methods: Analyses were performed in two different patient cohorts, one with poor glycemic control at baseline (mean glycated hemoglobin 9.0% [75 mmol/mol]) and a second cohort considered to be at increased risk of hypoglycemic events. Clinical input data and direct medical costs were sourced from published literature. The analysis was performed from a third-party payer perspective over patient lifetimes and future costs and clinical outcomes were discounted at 3.5% per annum. Results: In both patient cohorts, SAP was associated with a gain in quality-adjusted life expectancy but higher costs relative to CSII (incremental gain of 1.40 quality-adjusted life years [QALYs] in patients with poor baseline glycemic control and 1.73 QALYs in patients at increased risk of hypoglycemic events). Incremental cost-effectiveness ratios for SAP versus CSII were TRY 76,971 (EUR 11,612) per QALY gained for patients with poor baseline glycemic control and TRY 69,534 (EUR 10,490) per QALY gained for patients at increased risk for hypoglycemia. Conclusions: SAP is associated with improved long-term clinical outcomes versus CSII, and in Turkey, SAP is likely to represent good value for money compared with CSII in T1D patients with poor glycemic control and/or with frequent severe hypoglycemic events.

Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial.

BACKGROUND: Hypoglycaemia unawareness and severe hypoglycaemia can increase fear of hypoglycaemia and the risk of subsequent hypoglycaemic events. We aimed to assess the safety and efficacy of insulin pump therapy with integrated continuous glucose monitoring (CGM) and a suspend-before-low feature (Medtronic MiniMed 640G with SmartGuard) in hypoglycaemia-prone adults with type 1 diabetes. METHODS: SMILE was an open-label randomised controlled trial done in people aged 24-75 years with type 1 diabetes for 10 years or longer, HbA1c values of 5·8-10·0% (40-86 mmol/mol), and at high risk of hypoglycaemia (recent severe hypoglycaemia or hypoglycaemia unawareness defined by a Clarke or Gold score ≥4). Participants were enrolled from 16 centres (eg, clinics, hospitals, or university medical centres) in Canada, France, Italy, the Netherlands, and the UK. After baseline run-in phase (2 weeks), participants were randomly assigned to the MiniMed 640G pump (continuous subcutaneous insulin infusion) with self-monitoring of blood glucose (control group) or to the MiniMed 640G system with the suspend-before-low feature enabled (intervention group), for 6 months. The study statistician analysing the data was masked to group assignment until final database lock; because of the nature of the intervention, participants and treating clinicians could not be masked to group assignment. The primary outcome was the mean number of sensor hypoglycaemic events, defined as 55 mg/dL (3·1 mmol/L) or lower, and was analysed on an intention-to-treat basis in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, number NCT02733991, and is completed. FINDINGS: Between Dec 7, 2016, and March 27, 2018, 153 participants with a mean age 48·2 [12·4] years were randomly assigned: 77 to the control group (mean age 47·4 [12·5] years) and 76 to the intervention group (mean age 49·0 [12·2] years). After 6 months, the intervention group had significantly fewer hypoglycaemic events per participant per week (1·1 [SD 1·2] vs 4·1 [3·4] mean events, model-based treatment effect -2·9 [95% CI -3·5 to -2·3]; p<0·0001) and fewer severe hypoglycaemic events (instances requiring third-party assistance with carbohydrate or glucagon administration, or other resuscitative actions) overall (three vs 18; p=0·0036). The most common adverse events were hypoglycaemia (observed in ten [13%] of 77 participants in the control group vs four [5%] of 76 in the intervention group) and hyperglycaemia (observed in seven [9%] of 77 vs seven [9%] of 76). No serious adverse device effects or episodes of diabetic ketoacidosis were reported. INTERPRETATION: Insulin pump therapy with integrated CGM and a suspend-before-low feature reduced the frequency of sensor hypoglycaemic and severe hypoglycaemic events in hypoglycaemia-prone adults compared with use of continuous subcutaneous insulin infusion without real-time CGM. These results suggest that this technology could be beneficial in this high-risk population. FUNDING: Medtronic International Trading Sàrl and Medtronic Canada.

Cost-Effectiveness Analysis of the MiniMed 670G Hybrid Closed-Loop System Versus Continuous Subcutaneous Insulin Infusion for Treatment of Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop (HCL) systems combine continuous glucose monitoring with continuous subcutaneous insulin infusion (CSII) to continuously self-adjust basal insulin delivery. Relative to CSII, HCL improves glycemic control and reduces the risk of hypoglycemia but has higher acquisition costs. The aim of this analysis was to assess the cost-effectiveness of the MiniMed™ 670G HCL system versus CSII in people with type 1 diabetes (T1D) in Sweden. METHODS: Cost-effectiveness analysis, from a societal perspective, was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Clinical data were sourced from a study comparing the MiniMed 670G system with CSII in people with T1D. Cost data, expressed in 2018 Swedish krona (SEK), were obtained from Swedish reference prices and published literature. RESULTS: The MiniMed 670G system was associated with a quality-adjusted life-year (QALY) gain of 1.90 but higher overall costs versus CSII, leading to an incremental cost-effectiveness ratio (ICER) of SEK 164,236 per QALY gained. Use of the HCL system resulted in a lower cumulative incidence of diabetes-related complications. Higher HCL system acquisition costs were partially offset by reduced complication costs and productivity losses. In people with T1D poorly controlled at baseline, the MiniMed 670G system was associated with 2.25 incremental QALYs versus CSII, yielding an ICER of SEK 15,830 per QALY gained. CONCLUSIONS: The MiniMed 670G system was associated with clinical benefits and quality-of-life improvements in people with T1D relative to CSII. At a willingness-to-pay threshold of SEK 300,000 per QALY gained, this HCL system likely represents a cost-effective treatment option for people with T1D in Sweden.

Cost-Effectiveness of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections in Patients with Poorly Controlled Type 2 Diabetes in Finland.

INTRODUCTION: Although primarily utilized in type 1 diabetes, continuous subcutaneous insulin infusion (CSII) represents a useful treatment alternative for patients with type 2 diabetes who are unable to achieve good glycemic control despite optimization of multiple daily injections (MDI). The aim of the analysis reported here was to investigate the long-term cost-effectiveness of CSII versus MDI in type 2 diabetes patients with poor glycemic control in Finland. METHODS: The IQVIA CORE Diabetes Model was used to make long-term projections of the clinical and economic outcomes associated with CSII use in type 2 diabetes, based on clinical input data from the OpT2mise trial, which showed that CSII was associated with a 1.1% decrease in glycated hemoglobin (HbA1c) in patients with poor glycemic control at baseline. The analysis was performed from a societal perspective and the time horizon was that of patient lifetimes. Future costs and clinical outcomes were discounted at 3% per annum. RESULTS: Continuous subcutaneous insulin infusion was associated with a gain in quality-adjusted life expectancy of 0.32 quality-adjusted life-years (QALYs) compared with MDI (8.15 vs. 7.83 QALYs, respectively), as well as higher mean lifetime costs, resulting in an incremental cost-effectiveness ratio of Euro (EUR) 47,834 per QALY gained for CSII versus MDI. The higher treatment costs in the CSII group were partly mitigated by a 15% reduction in diabetes-related complication costs. Sensitivity analyses demonstrated that CSII was most cost-effective in patients with the highest baseline HbA1c values. CONCLUSION: In Finland, CSII is likely to represent a cost-effective treatment alternative for patients with type 2 diabetes with poor glycemic control despite optimization of MDI. In such patients, CSII is associated with improved clinical outcomes relative to MDI, with the higher acquisition costs partly offset by a lower lifetime incidence and cost of diabetes-related complications. FUNDING: Medtronic International Sàrl.

Cost-effectiveness of sensor-augmented insulin pump therapy vs continuous subcutaneous insulin infusion in patients with type 1 diabetes in the Netherlands.

AIM: The aim of this study was to perform a cost-effectiveness analysis to establish the cost-effectiveness of sensor-augmented pump therapy (SAP) with automated insulin suspension vs continuous subcutaneous insulin infusion (CSII) alone in patients with type 1 diabetes in the Netherlands. PATIENTS AND METHODS: The analysis was performed using the IQVIA CORE Diabetes Model (CDM) in two different patient cohorts: one with suboptimal glycemic control at baseline (mean age 27 years, mean baseline HbA1c 8.0% [64 mmol/mol]) and the other at increased risk of hypoglycemic events (mean age 18.6 years, mean baseline HbA1c 7.5% [58 mmol/mol]). Clinical input data were sourced from published literature, and the analysis was performed from the societal perspective. RESULTS: In patients with suboptimal baseline glycemic control, SAP improved quality-adjusted life expectancy by 1.77 quality-adjusted life years (QALYs) vs CSII (15.54 QALYs vs 13.77 QALYs) with higher lifetime costs (EUR 189,855 vs EUR 150,366), resulting in an incremental cost-effectiveness ratio (ICER) of EUR 22,325 per QALY gained. In this cohort, sensitivity analyses showed that the influence of SAP on fear of hypoglycemia (FoH) and baseline HbA1c were key drivers of results. In patients at increased risk of hypoglycemia, the gain in quality-adjusted life expectancy with SAP vs CSII was 2.16 QALYs (16.70 QALYs vs 14.53 QALYs) with higher lifetime costs (EUR 204,013 vs EUR 171,032) leading to an ICER of EUR 15,243 per QALY gained. In this patient group, findings were most sensitive to changes in assumptions relating to the incidence of severe hypoglycemic events in the CSII arm. CONCLUSION: For type 1 diabetes patients in the Netherlands who do not achieve target HbA1c levels or who experience frequent severe hypoglycemic events on CSII, switching to SAP is likely to be cost-effective.

Study of MiniMed 640G Insulin Pump with SmartGuard in Prevention of Low Glucose Events in Adults with Type 1 Diabetes (SMILE): Design of a Hypoglycemia Prevention Trial with Continuous Glucose Monitoring Data as Outcomes.

BACKGROUND: Sensor-integrated pump systems with low-glucose suspend (also known as threshold suspend) functions have markedly transformed the management of type 1 diabetes, but most studies to date have excluded patients at high risk of hypoglycemia. The SMILE study is investigating the efficacy of the MiniMed™ 640G insulin pump with the SmartGuard™ predictive low-glucose management (PLGM) feature in the prevention of hypoglycemia in adults with type 1 diabetes, who are at high risk of hypoglycemia. METHODS: SMILE is a prospective, randomized, open-label, controlled trial being undertaken in four European countries and Canada. Following a 2-week run-in phase, eligible participants will be randomized to use either the MiniMed 640G system with continuous glucose monitoring (CGM) and the SmartGuard PLGM feature on continuously for 24 weeks (treatment arm), or the MiniMed 640G without CGM and with blinded continuous glucose measurements between weeks 10-12, 16-18, and 22-24 (control arm). The primary endpoint is the mean number of hypoglycemic events, defined as sensor glucose ≤55 mg/dL (≤3.0 mmol/L) for >20 consecutive minutes. Secondary endpoints include various glycemic indices in the hypoglycemic and hyperglycemic ranges, as well as glycated hemoglobin. Data on patient-reported outcomes such as hypoglycemia awareness and treatment satisfaction will also be collected. CONCLUSIONS: It is anticipated that the SMILE study will provide important insights into the effectiveness of SmartGuard technology in adult patients with type 1 diabetes.

Cost-Effectiveness Analysis of Sensor-Augmented Insulin Pump Therapy with Automated Insulin Suspension Versus Standard Insulin Pump Therapy in Patients with Type 1 Diabetes in Sweden.

INTRODUCTION: In Sweden an estimated 10,000 people with type 1 diabetes use continuous subcutaneous insulin infusion (CSII). Sensor-augmented pump therapy (SAP) is associated with higher acquisition costs but provides additional clinical benefits (e.g. reduced rate of hypoglycemic events) over and above that of CSII alone. The aim of the analysis was to assess the cost-effectiveness of SAP with automated insulin suspension relative to CSII alone in two different groups of patients with type 1 diabetes in Sweden. METHODS: Cost-effectiveness analyses were performed using the QuintilesIMS CORE Diabetes Model, with clinical and economic input data derived from published literature. Separate analyses were performed for patients at increased risk of hypoglycemia and for patients with uncontrolled glycated hemoglobin (HbA1c) at baseline. Analyses were performed from a societal perspective over a lifetime time horizon. Future costs and clinical outcomes were discounted at 3% per annum. RESULTS: SAP with automated insulin suspension was associated with an incremental gain in quality-adjusted life expectancy versus the CSII of 1.88 quality-adjusted life years (QALYs) in patients at high risk of hypoglycemia and of 1.07 QALYs in patients with uncontrolled HbA1c at baseline. Higher lifetime costs for SAP with automated insulin suspension resulted in projected incremental cost-effectiveness ratios for the SAP with automated insulin suspension versus CSII of Swedish Krona (SEK) 139,795 [euros (EUR) 14,648] per QALY gained for patients at increased risk for hypoglycemia and SEK 251,896 (EUR 26,395) per QALY gained for patients with uncontrolled HbA1c. In both groups, SAP with automated insulin suspension also reduced the incidence of diabetes-related complications relative to CSII. CONCLUSIONS: In Sweden, SAP with automated insulin suspension likely represents a cost-effective treatment option relative to CSII for the management of patients with type 1 diabetes with a history of severe hypoglycemic events or patients who struggle to achieve good glycemic control despite the use of CSII. FUNDING: Medtronic International Trading Sàrl.

Factors associated with improved glycemic control following continuous subcutaneous insulin infusion therapy in patients with type 2 diabetes uncontrolled with bolus-basal insulin regimens: An analysis from the OpT2mise randomized trial.

This analysis investigated factors associated with the decrease in HbA1c in patients receiving continuous subcutaneous insulin infusion (CSII) in the OpT2mise randomized trial. In this study, patients with type 2 diabetes and HbA1c >8% following multiple daily injections (MDI) optimization were randomized to receive CSII (n = 168) or MDI (n = 163) for 6 months. Patient-related and treatment-related factors associated with decreased HbA1c in the CSII arm were identified by univariate and multivariate analyses. CSII produced a significantly greater reduction in HbA1c than MDI, and the treatment difference increased with baseline HbA1c. In the CSII arm, the only factors significantly associated with decreased HbA1c were higher baseline HbA1c (P < .001), geographical region (P < .001), higher educational level (P = .012), higher total cholesterol level (P = .002), lower variability of baseline glucose values on continuous glucose monitoring (P < .001) and the decrease in average fasting self-monitored blood glucose at 6 months (P < .001). These findings suggest that CSII offers an option to improve glycemic control in a broad range of patients with type 2 diabetes in whom control cannot be achieved with MDI. OpT2mise ClinicalTrials.gov number: NCT01182493 (https://clinicaltrials.gov/).

The Impact of Insulin Pump Therapy on Glycemic Profiles in Patients with Type 2 Diabetes: Data from the OpT2mise Study.

BACKGROUND: The OpT2mise randomized trial was designed to compare the effects of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) on glucose profiles in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with glycated hemoglobin (HbA1c) levels of ≥8% (64 mmol/mol) and ≤12% (108 mmol/mol) despite insulin doses of 0.7-1.8 U/kg/day via MDI were randomized to CSII (n=168) or continued MDI (n=163). Changes in glucose profiles were evaluated using continuous glucose monitoring data collected over 6-day periods before and 6 months after randomization. RESULTS: After 6 months, reductions in HbA1c levels were significantly greater with CSII (-1.1±1.2% [-12.0±13.1 mmol/mol]) than with MDI (-0.4±1.1% [-4.4±12.0 mmol/mol]) (P<0.001). Similarly, compared with patients receiving MDI, those receiving CSII showed significantly greater reductions in 24-h mean sensor glucose (SG) (treatment difference, -17.1 mg/dL; P=0.0023), less exposure to SG >180 mg/dL (-12.4%; P=0.0004) and SG >250 mg/dL (-5.5%; P=0.0153), and more time in the SG range of 70-180 mg/dL (12.3%; P=0.0002), with no differences in exposure to SG<70 mg/dL or in glucose variability. Changes in postprandial (4-h) glucose area under the curve >180 mg/dL were significantly greater with CSII than with MDI after breakfast (-775.9±1,441.2 mg/dL/min vs. -160.7±1,074.1 mg/dL/min; P=0.0015) and after dinner (-731.4±1,580.7 mg/dL/min vs. -71.1±1,083.5 mg/dL/min; P=0.0014). CONCLUSIONS: In patients with suboptimally controlled type 2 diabetes, CSII significantly improves selected glucometrics, compared with MDI, without increasing the risk of hypoglycemia.