Hybrid closed loop systems for managing blood glucose levels in type 1 diabetes

It is estimated that approximately 400,000 people in the UK are living with type 1 diabetes, including around 29,000 children. In type 1 diabetes, a person's blood glucose level becomes too high (hyperglycaemia) because there is no, or very little, production of insulin by the pancreas. Blood glucose levels can only be regulated by giving insulin to prevent hyperglycaemia. If type 1 diabetes is not well controlled, people are at increased risk of long-term complications of hyperglycaemia, including microvascular damage such as retinopathy and blindness, nephropathy and neuropathy. They are also at increased risk of macrovascular complications such as ischaemic heart disease, stroke and peripheral vascular disease.

The goal of treating type 1 diabetes is to keep blood glucose within a healthy range by providing the body with supplemental insulin. If the level of circulating insulin becomes too high, blood glucose levels can become too low leading to hypoglycaemia (also known as a hypo).

Managing type 1 diabetes usually involves:

• regularly measuring blood glucose levels

• multiple daily insulin injections or continuous subcutaneous insulin infusion (CSII)

• lifestyle adjustments

• periodic assessment of blood glucose control.
  
  Blood glucose monitoring can be done by self-monitoring (capillary blood testing), or by real-time continuous (rtCGM) or intermittently scanned continuous glucose monitors (isCGM). Long term monitoring of blood glucose control can be done by measuring HbA1c level, which reflects the average plasma glucose over the last 8 to 12 weeks. Time in range is a measure of blood glucose control that shows the percentage of time a person spends within a target glucose range (3.9 to 10 mmol/litre). Time below range (less than 3.9 mmol/litre) is associated with increased risk of severe hypoglycaemia. Time above range (more than 10 mmol/litre) indicates increased risk of complications and diabetic ketoacidosis.

NICE's recommendations on blood and plasma glucose in type 1 and type 2 diabetes in children and young people, type 1 diabetes in adults and diabetes in pregnancy recommend that people with type 1 diabetes should aim for a target HbA1c level of 48 mmol/mol (6.5%) or lower, or an individualised target set in pregnancy, to minimise the risk of long-term complications from diabetes. In practice, an individualised HbA1c target, taking into account the risk of hypoglycaemia, may be agreed with people with diabetes and carers.

Hybrid closed loop (HCL) systems use a mathematical algorithm to deliver insulin automatically in response to continuously monitored interstitial fluid glucose levels. They use a combination of real-time glucose monitoring from a continuous glucose monitor (CGM) device and a control algorithm to direct insulin delivery through CSII. Different HCL systems are available, and some are built by combining interoperable components from different companies. Because of the large number of combinations of components available to the NHS, this appraisal considers HCL systems as a class of technologies rather than individual components or systems. Expert advice received by NICE during scoping suggested that in practice, minimal differences in outcomes would be expected between systems if used as intended. The choice of components or system is based on a person's preference and whether the system has the appropriate licence for use. Whether HCL systems are licensed for use in pregnancy or in children or young people may differ. Any future systems comprised of components from different manufacturers must show interoperability and be equivalent to current systems in terms of patient benefits.

At the time of scoping the following systems and interoperable components were available:

• SmartGuard control algorithm (Medtronic) with Guardian 4 CGM sensor (Medtronic) and MiniMed 780G insulin pump (Medtronic). These components are not available for use with components from other companies.

• Control IQ control algorithm (Tandem Diabetes Care/Air Liquide) with Dexcom G6 CGM sensor (Dexcom) and t:slim X2 insulin pump (Tandem Diabetes Care/Air Liquide).

• CamAPS FX control algorithm (CamDiab) with Dexcom G6 CGM sensor (Dexcom) and either:

  • DANA i insulin pump (Advanced Therapeutics UK Ltd) or

  • mylife YpsoPump (Ypsomed).
    
    This is not an exhaustive list, and other systems and interoperable components are available.

There are 2 comparators:

• CSII plus rtCGM (non-integrated)

• CSII plus isCGM (non-integrated).

A range of HCL systems is available from different companies. Individual components of different systems are sometimes combined. The external assessment group received NHS supply chain costs for the various systems at April 2023 prices. A clinical expert provided market share estimates for the different systems. The appraisal model base case used a weighted average of the 4‑year cost from various companies. This resulted in a 4‑year total cost of £22,735 and an average annual cost of £5,684.

To give an incremental cost-effectiveness ratio of £20,000 per quality-adjusted life year gained, the companies will need to agree discounts with NHS England, on behalf of the relevant health bodies, for HCL systems to be procured by the NHS. The size of the discounts will be commercial in confidence.