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

Abstract

Introduction:

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.

Introduction

In 2015, around 25,000 people living in Greece were estimated to have type 1 diabetes (T1D).¹ While there is a paucity of data surrounding the economic burden of T1D in Greece, it has been estimated that the annual diabetes-related direct costs per patient amount to EUR 2712 in pediatric patients with T1D, suggesting that the economic burden associated with T1D could be in excess of EUR 67 million each year.² Drivers of economic burden include diabetes-related complications and severe hypoglycemic event (SHEs) costs, in addition to the costs of treating T1D.^2,3

Comparison of the EU5 countries showed that diabetes drugs account for only a small proportion of all direct diabetes costs, accounting for a maximum of 10.5% of direct diabetes costs. The total annual cost of patients with diabetes ranged from EUR 5.5 billion in Spain to EUR 43.2 billion in Germany (in 2010 EUR), with inpatient care costs accounting for a minimum of 34% of direct costs, the largest component in all five countries.⁴

In Italy, the presence of one complication in a patient with T1D increased the annual direct cost by 16% compared with a patient with no complication, but in patients with three or more complications, the annual direct cost was 120% higher. These increased costs were attributed to increased hospitalization and drug costs.⁵ Similarly, in United Kingdom, 80% of the direct cost of diabetes is attributed to complications.⁶ Diabetes-related complications account for large proportions of the cost of diabetes throughout Europe, and reductions in complications through improvements in treatment could partially alleviate the economic burden.

T1D is a chronic autoimmune disease characterized by insulin production deficiency, resulting in serious microvascular and macrovascular complications, besides hyperglycemia and hypoglycemia, if not managed effectively.⁷ The ultimate treatment goal in T1D is to mimic the normal physiologic action of the pancreas, through the production of insulin, resulting in blood glucose levels being maintained within the euglycemic range. As seen in people without T1D, the treatment of T1D should also recognize and correct hyperglycemia and hypoglycemia as quickly as possible.⁸ There is currently no cure or means of prevention of T1D with patients needing to manage the disease for their lifetime using daily exogenous insulin administration to achieve glycemic control.^9,10

There is a well-established connection between glycemic control, measured by glycated hemoglobin (HbA1c), and long-term serious health complications in diabetes. The microvascular benefits of glycemic control were shown in the Diabetes Control and Complications Trial (DCCT). The DCCT was a prospective randomized controlled trial in patients with T1D comparing intensive (mean HbA1c about 7% [53 mmol/mol]) versus standard (mean HbA1c about 9% [75 mmol/mol]) glycemic control. Improved glycemic control was associated with 50%–76% reductions in rates of development and progression of microvascular complications (retinopathy, neuropathy, and diabetic kidney disease).¹¹ The persistence of microvascular benefits over two decades was shown in the glycemic Epidemiology of Diabetes Interventions and Complications (EDIC) study, a follow-up of the DCCT cohorts.¹²

Despite the importance of glycemic control and major advances in diabetes treatment and technology, achieving glycemic control remains a challenge in people with T1D.¹³ In Greece, only one-third of children with T1D have HbA1c below 7.5%, with a further third having HbA1c levels between 7.5% and 8.5%.² Glycemic control of children using an insulin pump has been shown to be better than those using other treatment regimens (HbA1c: 7.2% vs. 8.3%, t = −2.101, P = 0.039).² Despite the improved glycemic control, the reported insulin pump usage in Greece remains low, with estimates around 10% in children, and 10% and 17% in males and females older than 25 years, respectively.^2,13 There is a need, therefore, for wider access and utilization of advanced insulin delivery systems, which are proven to optimize glycemic control for people with T1D, in Greece.

With a view to better understanding the potential health economic implications of insulin pump therapy in Greece, the aim of these analyses was to perform a long-term health economic analysis of the MiniMed 780G system compared with the MiniMed 640G system and multiple daily injections (MDI) plus intermittently scanned continuous glucose monitoring (isCGM) in people with T1D in Greece.

The MiniMed 780G system is an advanced hybrid closed-loop (AHCL) system that automatically self-adjusts insulin delivery every 5 min, guided by the use of real-time continuously measured glucose.^14,15 In clinical studies,^14
–16 the MiniMed 780G system was associated with improvements in HbA1c, which indicates long-term glycemic control, and time-in-range (TIR), a measure of the percentage of time spent in the glucose range of 70–180 mg/dL (3.9–10.0 mmol/L),¹⁷ which represents short-term glycemic control, compared with previous generation devices and other insulin delivery methods.¹⁴

The MiniMed 640G system is a sensor-augmented pump (SAP) system that automatically stops insulin delivery when glucose is predicted to approach a low limit (predictive low glucose management [PLGM]) and restart it upon recovery, which helps reducing hypoglycemic events by up to 83% of stand-alone insulin pump treatment.¹⁸ The MiniMed 640G system helps eliminating hypoglycemia even for problematic, hypo-prone cohorts, without deterioration in glycemic control.^19
–21

IsCGM technology provides information on real-time glucose levels and glucose trends when scanned by the user, which can be used in combination with MDI or with insulin pumps for the treatment of T1D.²² MDI plus isCGM has been shown to reduce time in hypoglycemia compared with self-monitoring of blood glucose (SMBG) by 38%.²³ Recent real-world comparison of hybrid closed-loop (HCL) systems with SAP plus PLGM and MDI plus continuous glucose monitoring (CGM) showed that patients using HCL systems experienced significantly increased TIR, and significantly reduced time in hypoglycemia, compared with patients using SAP plus PLGM and patients using MDI plus CGM/isCGM. Patients using HCL systems also experienced significantly reduced time in hyperglycemia than patients using MDI plus CGM as a method of diabetes management.²⁴

Methods

Model structure

The analyses were performed using the IQVIA CORE Diabetes Model (CDM; IQVIA, Basel, Switzerland), a published and validated nonproduct-specific model that can be used in T1D and type 2 diabetes.^25
–27 The CDM simulates the progression of diabetes and diabetes-related complications based on a series of interdependent submodels. Outcomes of the CDM include undiscounted life expectancy and quality-adjusted life expectancy, cumulative incidence and time to onset of long-term complications, direct and indirect costs, and the incremental cost-effectiveness ratio (ICER).

Simulation cohort and treatment effects

AHCL versus SAP plus PLGM

Baseline cohort characteristics and treatment effects for the comparison of the MiniMed 780G system, AHCL, with the MiniMed 640G system, SAP plus PLGM, were sourced from the MiniMed 780G US Pivotal study.^14,28 The mean (standard deviation [SD]) age of the cohort was 38.3 (17.6) years, mean (SD) duration of diabetes was 23 (13) years, and mean HbA1c at baseline was 7.5% (Table 1).²⁸ After 3 months using the MiniMed 780G system, mean HbA1c was reduced from 7.5% at baseline to 7.0% and no SHE was reported. The event rate for ketoacidosis and severe hypoglycemia was assumed to be zero in both treatment arms, in line with published data.¹⁴

Table 1.

Baseline Characteristics of Simulation Cohort

	AHCL versus SAP plus PLGM	AHCL versus MDI plus isCGM
Age, years	38.3 (17.6)	45.8 (15.3)
Male, %	45.2	53.9
Diabetes, years	23 (13)	22.8 (13.7)
HbA1c, %	7.5	7.8

Values are mean (SD) unless otherwise specified.

AHCL, advanced hybrid closed loop; HbA1c, glycated hemoglobin; isCGM, intermittently scanned continuous glucose monitoring; MDI, multiple daily injections; PLGM, predictive low glucose management; SAP, sensor-augmented pump; SD, standard deviation.

AHCL versus MDI plus isCGM

For the comparison of the MiniMed 780G system, AHCL, with MDI plus isCGM, baseline cohort characteristics were sourced from the prospective observational real-world cohort study of people with T1D using isCGM.²⁹ The mean (SD) age of the cohort was 45.8 (15.3) years, mean (SD) duration of diabetes was 22.8 (13.7) years, and mean HbA1c at baseline was 7.8% (Table 1).²⁹ Key treatment effects were sourced from various studies.^14,28

–31 After 3 months using the MiniMed 780G system, patients with baseline HbA1c of 7.8% were reduced to 7.0%, and no SHE was reported.^14,28,30 Therefore, ketoacidosis and SHE rates were assumed to be zero in the AHCL arm.^14,28 In the MDI plus isCGM arm, HbA1c was assumed to remain at baseline.²⁹ SHE and ketoacidosis event rates were assumed to be 63.9/100 patient-years and 2.59/100 patient-years, respectively.^29,31

Costs and utilities

The analyses were performed from the societal perspective and included direct and indirect costs associated with diabetes-related complications. Direct costs associated with diabetes-related complications were sourced from published literature and local expert opinion (Table 2).^3,34 Indirect costs associated with lost productivity were based on the human capital approach and included average annual salaries for Greece and days off due to diabetes-related complications, which were derived from various European sources.^32,35

Table 2.

Direct Costs Associated with Diabetes-Related Complications

Event	Cost, EUR	References
Myocardial infarction, year of event	4488	Tzanetakos et al.³⁴
Myocardial infarction, subsequent years	1959	Tzanetakos et al.³⁴
Angina, year of event	3603	Tzanetakos et al.³⁴
Angina, subsequent years	1194	Tzanetakos et al.³⁴
Congestive heart failure, year of event	2925	Tzanetakos et al.³⁴
Congestive heart failure, subsequent year	1394	Tzanetakos et al.³⁴
Stroke, year of event	4394	Tzanetakos et al.³⁴
Stroke, subsequent years	1971	Tzanetakos et al.³⁴
Stroke death within 30 days	3665	Tzanetakos et al.³⁴
Peripheral vascular disease, year of onset	4153	Expert opinion
Peripheral vascular disease, subsequent years	1341	Expert opinion
Hemodialysis, first year	39,441	Tzanetakos et al.³⁴
Hemodialysis, annual	38,664	Tzanetakos et al.³⁴
Peritoneal dialysis, annual	24,304	Expert opinion
Renal transplant, year of event	40,231	Expert opinion
Renal transplant, subsequent years	9543	Expert opinion
Minor hypoglycemic event	0	Assumed to be zero
Severe hypoglycemic event (not requiring medical assistance)	43	Jakubczyk et al.³
Severe hypoglycemic event (requiring medical assistance)	776	Jakubczyk et al.³
Laser photocoagulation	5013	Expert opinion
Cataract operation	10,503	Expert opinion
Cataract operation follow-up	1811	Expert opinion
Blindness, year of onset	11,249	Tzanetakos et al.³⁴
Blindness, subsequent years	6183	Tzanetakos et al.³⁴
Neuropathy, year of onset	2242	Expert opinion
Neuropathy, subsequent years	1218	Expert opinion
Amputation	5819	Tzanetakos et al.³⁴
Prosthesis	8155	Expert opinion
Gangrene treatment	2967	Expert opinion
Healed ulcer follow-up	1048	Expert opinion
Infected ulcer	3841	Expert opinion
Uninfected ulcer	500	Expert opinion
Healed ulcer, history of amputation	1467	Tzanetakos et al.³⁴

Cost data are expressed in 2015 EUR.

EUR, euro.

Mean annual treatment costs were calculated at EUR 7507.76 for the AHCL arm, EUR 7301 for the SAP plus PLGM arm, and EUR 2940 for the MDI plus isCGM arm. In both AHCL and SAP plus PLGM arms, the insulin pump part of the systems was assumed to be replaced once every 5 years, and costs also included sensors (assuming a use of 50 sensors per year), as well as the cost of short-acting insulin and SMBG strips and lancets, in line with the Greek National Organization for the Provision of Health Services (EOPYY) regulations. Treatment costs associated with the MDI plus isCGM arm included sensors (assuming a use of 26 per year), short- and long-acting insulin, and needles.

Utilities associated with diabetes-related complications were obtained from published literature.^33,36
–38 In the AHCL versus SAP plus PLGM analysis, no fear of hypoglycemia (FoH) utility was applied due the SHE rate being assumed to be 0 in both arms, while in the AHCL versus MDI plus isCGM analysis, a special utility benefit associated with reduced FoH was incorporated into the analysis.

Therefore, in the MiniMed 780G versus MDI plus isCGM analysis, an annual utility benefit of 0.0552 was applied to the AHCL arm due a reduction in FoH, based on the INTERPRET study that demonstrated a 6.9 point decrease in the hypoglycemic fear survey (HFS) reported for people using sensor-augmented insulin pump therapy, as well as on an earlier study reporting that a 1 U increase in HFS score corresponded to a utility decrement of 0.008.^39
–41 The MDI plus isCGM arm had no significant improvement HFS score reported in the FUTURE study; therefore, no utility improvement was assumed.²⁹

Sensitivity analyses

A series of one-way sensitivity analyses was performed to determine key drivers of results. For both SAP plus PLGM and MDI plus isCGM comparisons, sensitivity analyses were performed around assumptions relating to the baseline HbA1c, intervention effect, and incidence of SHEs; and the quality-of-life (QoL) benefit associated with reduced FoH in the AHCL versus MDI plus isCGM analysis.

Time horizon, perspective, and discount rate

The analyses were performed from a societal perspective, including direct and indirect costs, and with a time horizon set to the remaining lifetime of patients. The discount rate applied to the economic and clinical outcomes was 1.5%, in line with the recent inflation rate in Greece.

Results

Comparison of AHCL with SAP plus PLGM

In the base case analysis, the MiniMed 780G system, AHCL, was associated with an increase in quality-adjusted life expectancy of 0.284 quality-adjusted life years (QALYs) compared with the MiniMed 640G system, SAP plus PLGM. Mean total lifetime costs were EUR 10,173 lower in the AHCL arm compared with the SAP plus PLGM arm (EUR 428,869 vs. EUR 439,042), due to the higher treatment costs associated with treatment in the AHCL arm being offset by savings due to reduced complications (Table 3). Therefore, the AHCL system is likely to be cost saving compared with the MiniMed 640G system.

Table 3.

Summary of 780G Versus 640G Base Case Results

	AHCL	SAP plus PLGM	Difference
Quality-adjusted life expectancy, QALYs	19.165	18.881	0.284
Total costs	431,262	441,566	–10,304
Total indirect costs	2393	2524	–131
Total direct costs	428,869	439,042	–10,173
Treatment^a	212,539	204,999	–7540
Management^b	10,123	10,132	–9
Cardiovascular disease	28,976	29,511	–535
Renal disease	62,436	67,746	–5310
Ulcer/amputation/neuropathy	23,606	27,028	–3422
Ophthalmic complications	91,161	99,597	–8436
Hypoglycemia	0	0	0
ICER, EUR per QALY gained	–36,307

Treatment costs include costs associated solely with the treatment of diabetes.

Management costs include costs outside of diabetes treatment that are not attributable to complications.

ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

Sensitivity analyses showed that the findings of the analysis were sensitive to changes in assumptions around time horizon, number of SMBG used, and well-controlled HbA1c at baseline with minimal HbA1c reduction. The AHCL system was shown to not be cost saving at a 5- and 10-year time horizon, but remained cost saving at a 20- and 40-year time horizon. Decreasing the assumed number of SMBG strips used by patients in the AHCL arm from 200 to 120 strips/month increased the cost savings from EUR 10,173 in the base case to EUR 20,261. When patients were assumed to have a baseline HbA1c of 7% and a reduction in HbA1c of 0.2% following intervention, the ICER increased to EUR 2251 per QALY gained.

Comparison of AHCL with MDI plus isCGM

In the base case analysis, the MiniMed 780G system, AHCL, was associated with an increase in quality-adjusted life expectancy of 2.708 QALYs compared with MDI plus isCGM. Mean total lifetime costs were EUR 368,883 in the AHCL arm compared with EUR 287,564 in the MDI plus isCGM arm, resulting in EUR 76,396 higher costs in the AHCL arm. Higher treatment costs associated with the AHCL arm were partially offset by the savings due to reductions in diabetes-related complications. This resulted in an ICER of EUR 29,869 per QALY gained for the AHCL system versus MDI plus isCGM. At a willingness to pay threshold of EUR 34,000 per QALY gained, the likelihood of the AHCL system to be cost-effective was 84.2% (Table 4).

Table 4.

Summary of 780G Versus Multiple Daily Injections Plus Intermittently Scanned Continuous Glucose Monitoring Base Case Results

	AHCL	MDI plus isCGM	Difference
Quality-adjusted life expectancy, QALYs	18.157	15,449	2.708
Total costs	370,681	289,800	80,880
Total indirect costs	1798	2236	–439
Total direct costs	368,883	287,564	76,396
Treatment^a	188,577	72,568	116,971
Management^b	8986	8951	36
Cardiovascular disease	28,299	28,760	–614
Renal disease	49,604	56,367	–8126
Ulcer/amputation/neuropathy	18,328	22,581	–5659
Ophthalmic complications	75,089	85,406	–13,280
Severe hypoglycemia (requiring medical assistance)	0	12,245	–12,245
Diabetic ketoacidosis	0	687	–687
ICER, EUR per QALY gained	29,869

Treatment costs include costs associated solely with the treatment of diabetes.

Management costs include costs outside of diabetes treatment that are not attributable to complications.

Sensitivity analyses showed that the findings of the analysis were sensitive to changes in assumptions around time horizon, FoH utility, SHE rate, and HbA1c reduction. As the time horizon decreased the ICER increased, and at a time horizon of 5 years, the ICER was EUR 42,160 per QALY gained. With a FoH utility half that of the base case, the QALY difference decreased to 2.015 and the ICER increased to EUR 40,147 per QALY/gained.

Similarly, changing the SHE rate (requiring medical assistance) in the MDI plus isCGM arm from 63.9/100 patient-years to 25/100 patient-years, and introducing an SHE rate (requiring nonmedical assistance) of 65/100-patient years, decreased the QALY difference to 2.480 and increased the ICER to EUR 35,352 per QALY gained. An assumed HbA1c reduction of 0.5%, compared with 0.8% in the base case, resulted in a QALY of EUR 34,287 per QALY gained, due to a decreased QALY benefit of 2.539 and an increased cost difference of EUR 80,881.

Discussion

The findings of the analyses suggest that the MiniMed 780G system is likely to be cost saving compared with the MiniMed 640G system and cost-effective compared with MDI plus isCGM in patients with T1D in Greece. Compared with the SAP plus PLGM system, the MiniMed 780G system was estimated to lead to an increase in quality-adjusted life expectancy of 0.28 QALYs and savings of EUR 10,173. Comparison of the MiniMed 780G system with MDI plus isCGM lead to an estimated 2.71 QALY increase in quality-adjusted life expectancy and an increase in total lifetime costs of EUR 76,396.

In both analyses, the treatment costs were higher in the MiniMed 780G arm, but reductions in costs associated with diabetes-related complications entirely offset the treatment costs when compared with the SAP plus PLGM system, and partially offset treatment costs when compared with MDI plus isCGM. Quantifying and understanding the cost-effectiveness of AHCL systems are paramount in increasing the uptake of AHCL usage.

This analysis is one of the first long-term cost-effectiveness analysis to compare long-term clinical and economic outcomes with the MiniMed 780G system, AHCL, versus the SAP plus PLGM system and MDI plus isCGM. As an AHCL system, the MiniMed 780G automatically* adjusts insulin delivery and corrects glucose levels every 5 min, thus helping to prevent highs and lows.^14,15

In clinical studies and supported by early real-world evidence, the MiniMed 780G system results in more patients achieving their glycemic targets.^28,42 In a clinical trial of patients with T1D 14–75 years of age, 84% of patients reached an HbA1c target of 7% using the MiniMed 780G system with optimal system settings, compared with 52% of patients at baseline.¹⁸ In addition, the proportion of patients achieving a TIR target of 70% increased from 45% at baseline to 79% when using the MiniMed 780G system.²⁸ Similarly, real-world analysis of the first 1000 users of the MiniMed 780G system showed that 82% of patients had an HbA1c below 7% and 80% of patients achieved a TIR of >70%.⁴²

The improvements in HbA1c and TIR associated with the MiniMed 780G system, compared with previous generation devices, has been shown in this analysis to translate to cost savings.¹⁴ Simultaneous comparison of the MiniMed 780G system with the SAP plus PLGM system and MDI plus isCGM outlines the clinical and health economic benefits of the AHCL system.

In addition, a recent European analysis investigating the real-life scanning frequency patterns and their association with glycemic parameters demonstrated that only few isCGM users are scanning frequently enough to reach the internationally recommended HbA1c and TIR targets.⁴³

Twenty-two percent of users performed more than 22 scans on average per day and 5% of users performed more than 48 scans on average per day, which are required to reach the glycemic targets of HbA1c and TIR, respectively.²⁰ Real-world evidence from Sweden has shown that only one in 20 new isCGM users reach an HbA1c below 7% due to the new device. Translating to an increase in the number of people with T1D reaching an HbA1c below 7% from 22% to 27% after 3 years.⁴⁴ Similarly, in an Italian real-world study of children with T1D, only 8.3% of patients using isCGM, plus MDI, achieved TIR >70%.⁴⁵ Therefore, for some patients, outside of the clinical setting, management using isCGM is not sufficient to achieve glycemic targets.

Sensitivity analyses showed that the FoH utility and SHE rate were key drivers of cost-effectiveness in the comparison of the AHCL system with MDI plus isCGM. Reducing the FoH utility value and decreasing the rate of SHEs that required medical attention in patients using MDI plus isCGM decreased the QALY difference between the two treatment regimens, increasing the ICER. In the comparison of AHCL system with SAP plus PLGM, baseline HbA1c and the treatment effect regarding HbA1c had a substantial impact of the ICER. Reducing the baseline HbA1c by 0.5% to 7% and using a treatment effect of 0.2%, instead of 0.5%, resulted in the AHCL system versus the SAP plus PLGM system being cost-effective, yet not cost saving. With an ICER of EUR 2251 per QALY gained, the AHCL system remained below the willingness to pay threshold.

In the AHCL versus MDI plus isCGM analysis, a substantial proportion of cost savings was derived from avoided SHEs in patients using the AHCL system. Data surrounding the costs of SHEs in Greece are scarce, but it is estimated that SHEs in patients with diabetes cost EUR 4.3 million annually, with direct and indirect costs accounting for EUR 3.5 million and EUR 0.8 million, respectively.³ The reduction in SHE associated with the AHCL system, compared with MDI plus isCGM, also incurs a QoL benefit associated with a reduction in FoH, which is relatively common in people with T1D.⁴⁶ FoH can impact multiple areas of people's lives, including the self-management of T1D.⁴⁷ The FoH can also be increased in people with history of SHEs, as well as in certain situations (e.g., while driving or in the workplace), and may act as a barrier to physical activity.^46,48,49

There can also be a psychological burden associated with FoH in people with T1D, which may also affect parents or caregivers of young children or adolescents with T1D.^50,51 An FoH utility was included in this analysis to represent the benefits associated with avoided SHEs in patients using the AHCL system, which go beyond the physical effects of SHEs. In sensitivity analyses, the FoH utility was shown to contribute to the cost-effectiveness of the AHCL system versus MDI plus isCGM.

A limitation of the analysis was the use of nonrandomized clinical studies and indirect comparisons of treatment effects as sources of clinical outcomes, due to a lack of currently available randomized studies and studies that included a direct comparison of appropriate therapies. Comparison of the AHCL system with SAP plus PLGM derived cohort data and treatment effects from a single-arm nonrandomized study,^14,28 while cohort data for the AHCL comparison with MDI plus isCGM were sourced from an observational real-world study of isCGM, with no direct AHCL comparison, and treatment effects were sourced from two different studies, both of which were single-arm nonrandomized studies.^14,28,29

In addition, this analysis used short-term clinical data to project outcomes over patient lifetimes in the absence of long-term projections, a method common to health economic analyses. The recently developed AHCL system lacks long-term, real-world data; therefore, long-term projections of clinical and cost outcomes relied on assumptions sourced from the Pivotal clinical trial, in line with recommendations in guidelines for computer modeling of diabetes interventions.⁵²

A further limitation is the difference in mean baseline age between the AHCL versus SAP plus PLGM comparison and the AHCL versus MDI plus isCGM comparison, which were 38.3 and 45.8 years, respectively. The difference in baseline age is due to the choice of data source, which were chosen due to being the most appropriate available data. The differences in baseline cohort mean that the analyses should not be directly compared, but as this analysis compared AHCL with more established treatments, the cohort differences should not greatly impact the conclusions drawn.

There is a paucity of national-level data on the use of diabetes technology, including isCGM and insulin pump devices, in Greece. A study of data collected between 2010 and 2013 showed a 10% and 17% uptake in insulin pumps by males and females older than 25 years, respectively.¹³ Therefore, current isCGM and insulin pump usage may be higher. Data from German and Austria suggest an increase in the use of insulin pumps and CGM.⁵³ In addition, in Sweden, the use of insulin pumps among people with T1D has increased from 18% to 25% between 2010 and 2019, with a total of 80% using sensor-based glucose monitoring in 2019.⁵⁴ While the proportion of people with T1D using insulin devices in Germany, Austria, and Sweden may not directly translate to usage figures in Greece, it is plausible that usage of diabetes technologies and devices has followed similar trends to that of other European countries.

Real-world studies have shown that the use of HCL systems, and the MiniMed 780G system in particular, can help patients achieve a TIR goal >70%.^24,42 Eighty percent of patients using the MiniMed 780G system were reported to have a TIR >70%, together with 82% reaching an HbA1c <7%, which is in line with clinical trial reports of 79% and 84% of patients achieving a TIR >70% and an HbA1c <7%, respectively.^28,42 In a real-world study of diabetes technologies, HCL systems were associated with a significantly increased TIR compared with MDI plus CGM and SAP plus PLGM, and a significantly reduced time in hypoglycemia compared with MDI plus CGM and SAP plus PLGM.²⁴

The real-world improvements in glycemic control may be occurring despite infrequent scanning of devices by users. Frequent scanning is needed to achieve the internationally recommended HbA1c and TIR targets. In a European real-world analysis, only 5% of users performed more than 48 scans per day, the rate required to achieve glycemic targets.⁴³

Overall, these analyses suggest that the MiniMed 780G system will be cost saving compared with the SAP plus PLGM system and cost-effective compared with MDI plus isCGM in patients with T1D in Greece. The long-term cost savings of the MiniMed 780G system compared with the SAP plus PLGM system could be attributed to reductions in diabetes-related complications associated with the MiniMed 780G system use, while the cost-effectiveness versus MDI plus isCGM was primarily driven by a projected reduction in the incidence of SHEs and the QoL benefit associated with reduced FoH.

Footnotes

Authors' Contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published.

Author Disclosure Statement

V.L., A.K., and E.K. are employees of Research Institute and Diabetes Center, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece. A.Z.O.S., S.d.P., M.I.B., and O.C. are employees of Medtronic International Trading Sàrl, Tolochenaz, Switzerland. H.S. is an employee of Ossian Health Economics and Communications, Basel, Switzerland, which received consulting fees to support preparation of the article.

Funding Information

The study was supported by funding from Medtronic International Trading Sàrl, Geneva, Switzerland. (Grant number: 102054/2020).

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