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

Abstract

In an article in the Journal of Diabetes Science and Technology, Arunachalum et al retrospectively analyzed glycemic outcomes, regarding the use of hybrid closed-loop (HCL) systems in individuals with type-1 diabetes (T1D) in the United States in a real-world evidence (RWE) setting. In clinical trials, diabetes technology has shown to improve time in range (TIR) as well as other glucose metrics. In the light of increasing the use of diabetes technology in the T1D population, why do we not see improvement in clinical outcomes? Is it cost-effective to increase the use diabetes technology? Does access to diabetes technology vary in the United States? There is a need for additional clinical studies evaluating the effectiveness of diabetes technology in T1D including health economic aspects.

Type 1 diabetes (T1D) has been shown to be associated with the development of both microvascular- and macrovascular complications. ¹ These long-term diabetic complications are associated with poor glycemic control and may lead to a significant elevated risk of both morbidity and excess mortality in individuals with T1D. ¹ Thus, it is important to reach the glycemic goals for this group of individuals.

The development and the implementation of diabetes technology are important components in the long-term disease management such as for diabetes care. ² Technology may offer new and innovative solutions aiming to reduce the burden of disease for the T1D individuals. Furthermore, diabetes technology, including digital health, has been shown to improve clinical both outcomes and reduce the healthcare needs for individuals with T1D. ³ The development of smart insulin pumps such as the hybrid closed-loop (HCL) systems allow automated stop of insulin infusion when sensor glucose levels fall, and there is a risk of hypoglycemia. The use of HCL systems in the management of subjects with T1D has grown rapidly.^4,5 Smart insulin pumps have been further developed with so called advanced hybrid closed-loop (AHCL) systems. These systems can, apart from the automated stop of insulin infusion, also increase the insulin infusion based on when the glucose sensor signal indicates hyperglycemia. There are currently three different AHCL systems approved by the Federal Drug Agency (FDA); MiniMed 780G, Tandem IQ Connect, and Omnipod 5. All these ACHL systems have shown excellent performance regarding increased time in range (TIR), especially prominent during nighttime but also reduced time in hypoglycemia/time below range (TBR) and improvements in glucose management indicator (GMI), and other important glucose metrics in clinical trials^6-9 and to some extent in real-world evidence (RWE) studies.^10,11

There is a growing number of different digital technologies available that can help healthcare professionals in decision-making within the field of T1D such as enable monitoring of lifestyles and pharmaceutical/technical interventions. ¹² These systems include the platforms (CareLinkTM and Glokoo), both widely used in clinical practice for downloading glucose sensors, insulin pumps (including HCL as well as AHCL systems).

Besides insulin administration devices such as insulin pumps, smart insulin pens have recently become available. Smart pens record both the timing and dose of insulin delivered, ¹³ and the data can be downloaded via the platforms CareLink^TM and Glokoo. In addition, these insulin administration devices can be combined with intermittently scanned (is-CGM) or real-time continuous glucose monitoring (rt-CGM) systems as well as with smartphone applications and have been shown to reduce HbA1c, improve glucose metrics and be cost-effective. ¹⁴

During the five last years in United States both continuous glucose monitoring (CGM) systems and the use of insulin pumps have increased from 7% to 30% and 57% to 63%, respectively. ¹⁵ However, from the T1D exchange database, it has been reported that only 17% of the youth and 21% of the adult individuals with T1D achieved the American Diabetes Association (ADA) HbA1c goal of <7.5% and <7.0%, respectively.

Why is there no more clear association between increased use of diabetes technology and clinical outcome such as HbA1c? A possible explanation could be the nonoptimal use of the diabetes technology. Arunachalum et al showed in their real-world data with voluntarily uploaded CGM data from CareLink^TM that not all individuals used this function, and there was an association between percentage of time in Auto Mode and improved glycemic control. ⁴ Also, an association with increased insulin dose delivered as well as improvement in most glycemic metrics after Auto Mode initiation after Auto Mode initiation. ⁴ This points out the importance of aiming for a high use of Auto Mode for the HCL systems.

Arunachalum et al concluded that in real-world use in the United States, there was an association with the improvement of both GMI, TIR, and other glycemic metrics for most users of the HCL system. However, there are several limitations with the retrospective analysis in their observational retrospective study. ⁴ There was no randomization or any control group. There is no information on demographics or medical history of the participants in the study. Data upload frequency to the CareLink^TM system was dependent on the individual with diabetes or his/her family member. ⁴ Furthermore, only Medtronic devices can be uploaded in the CareLink^TM system and other HCL- and AHCL systems were therefore not included in the analysis by Arunachalum et al.

There could be several possible barriers against reaching improved glucose control in individuals with T1D. Poor education of diabetes technology of either the individuals with TID, and/or the health care providers (HCP), can be hinders to the successful implementation of diabetes technology. ¹⁶ Also, in some settings, the costs for diabetes technology could be a limiting factor for some patient populations.

What data do we need to make the best use of advanced diabetes technology? For health care payers, health economic analyses are increasingly being used to support healthcare decision-making. ¹⁷ An example of such a method is a cost-effectiveness analysis where simulated data on the projected health gains and resource needed. ¹⁸ However, cost-effectiveness analysis is often difficult regarding technical devices because there often is a short time between different device generations and hindering long-term health economic evaluations.

Conclusions

The use of HCL system in the United States has in RWE demonstrated an overall glycemic control in line with the HCL pivotal trial outcomes. But why have we not seen corresponding improvements in the clinical outcomes in line with the increased use as well as improved accessibility of diabetes technology? What are the barriers? Are the HCL systems used in the optimal patients’ cohorts or should be increase the use of AHCL systems?

The result of the study from Arunachalum et al is inspiring and calls for an effort to optimize the use of diabetes technology aiming to improve the glucose control and health among pediatric and adult individuals with T1D in the United States.