Automated insulin delivery in the real world
Automated insulin delivery (AID) within hybrid closed loop systems is starting to take centre stage in diabetes management. Findings from recent AID studies in a real-world setting in France, Belgium and England were presented at the recent Advanced Technologies & Treatments for Diabetes (ATTD) conference. Dr Susan Aldridge reports.
“Glucose control in children with type 1 diabetes is a real challenge,” said Professor Eric Renard of the Montpellier University Hospital. “The T1D Exchange Registry shows that in the age range of six to 12, barely 25% are reaching the old glucose target of 7.5% and now that it’s revised down to 7%, it’s likely to be even less. The reason is that children have greater variability in their insulin needs, especially at night, and it’s very difficult to meet this challenge without closed loop.”
He’s been involved in a study, in collaboration with the University of Virginia, of long-term follow-up of the Free-life AID system, which uses the Control-IQ algorithm in a cohort of 120 French children. While it was to be expected that the main benefit of hybrid closed loop (HCL) would be improved night-time glucose control, there was also an important question over whether HCL was safe and effective when used at school.
The first part of the study was a randomised controlled trial of HCL used 24/7 versus HCL used only at dinner and night-time, reverting to an open loop system during the day. The primary outcome was time in range (TIR) and the secondary outcome was the usual related continuous glucose monitor (CGM) metrics, plus HbA1c.
The HCL system consisted of the Control IQ algorithm with a t:slim X2 insulin pump and a Dexcom G6 CGM. The unique features of this algorithm, which has web-based software, are automated insulin correction boluses administered with the CGM estimate of the person’s glucose status, as well as basal-state modulation. There is also a dedicated hypoglycaemia safety system, which attenuates smoothly or discontinues insulin delivery using CGM and insulin on board information. Glucose control is gradually intensified overnight to achieve a level of 110-120 mg/dl in the morning.
There were 60 children aged between six and 12 in each group, all with more than one year’s duration of type 1 diabetes and with HbA1c less than 10% (86 mmol/mol). “We found that if you use the hybrid closed loop 24/7, you have a larger increase in TIR over dinnertime plus night-time use,” said ProfessorRenard. “Both groups improve their overnight glucose but the 24/7 group had better overall control. All the children improved and those with the worst control at the start improved the most by a mean of 20% TIR with 24/7 use and 18.5% with dinnertime plus night-time use.”
There were no cases of diabetic ketoacidosis (DKA), no hospital admissions, no severe hypos and the participants were able to carry out their usual school, sport and leisure activities.
In summary, 24/7 use of HCL is more effective at improving TIR than more limited use and HCL improves TIR, whatever the participant’s baseline glucose control.
An extension study is now using HCL 24/7 for the whole group to look for sustained improvement in glucose control – so far, this has shown 67% TIR and only 2.6% time below range (TBR), on average. The extension has continued and the group has now had more than 24 months of HCL use. Night-time metrics were even better at 82% TIR and just 1.4% TBR.
Furthermore, HbA1c improved very quickly, from 7.7% (61 mmol/mol) down to 7.2% (55 mmol/mol) and this was sustained over two years with the Control IQ system, during which time 45% of the children entered puberty but still kept very good control. “This is unusual in type 1 diabetes practice, where puberty is usually associated with poor control,” said Professor Renard.
These promising findings suggest that using AID in a 24/7 real-world setting – at school, leisure, home and overnight – goes a long way to meeting the glucose-control challenges faced by children and adolescents with type 1 diabetes.
AID in Belgium
In Belgium, all diabetes treatments are reimbursed. All devices are reimbursed too, but under strict criteria, with AID and pumps only for people with type 1 diabetes. The country’s healthcare system has a fixed budget for diabetes technology, which is only available in a hospital setting and in specific centreswhere the education and devices are provided by the hospital – there is no intermediary service provider, as there is elsewhere.
The systems they use combine the Medtronic Minimed 780G or Tandem t:slim pumps with control IQ and the Dexcom G6 CGM and the Diabeloop DBLG1 closed loop system, with Accuchek Insight and the Dexcom G6. “Health authorities in Belgium ask centres to conduct real-life studies of diabetes technology to judge the relevance of the treatment and sustainability of ongoing provision,” said Professor Régis Radermecker, diabetologist at the University Hospital, Liège. “Although there is more paperwork in this approach, it allows thought to be given to our way of working and we also obtain consistent real-world data.”
One of these required studies was the first real-world study of CGM in 2018. Then came the first Belgian real-world study of AID with the Minimed 670G, which showed mean increase in TIR of 9.9%, and now there are even better findings with the Minimed 78OG with TIR up 12% and glucose management indicator down by -0.5%.
Then there is the new study on the Diabeloop system with the DBLG1 closed-loop algorithm – said to be a major step towards full automation of closed loop – which has recently become available in Belgium. This will take place in 13 centres across Belgium, France and Germany. Belgium’s nationwide state-funded model of real-world AID research promises to lead to an extensive rollout of the technology, which should improve quality of life and outcomes in the country’s type 1 diabetes population.
AID in England
In England, fewer than one in 10 people with type 1 diabetes meet the target HbA1c of 6.5% (48 mmol/mol), according to National Diabetes Audit figures. And even using the Freestyle Libre, only 16% met both the greater than 70% TIR and less than 4% TBR targets. “This is not because they’re not ‘doing enough’, it’s because type 1 diabetes is fundamentally a difficult condition to manage,” said Dr Emma Wilmot, Associate Professor at the University of Nottingham. “We desperately need additional technologies to support people to reach their goals.”
In England and Wales at the moment, you need to get funding to secure the component parts of an AID system. Last year, the National Institute for Health and Care Excellence (NICE) recommended real-time CGM as cost-effective for all people with type 1 diabetes. “If only the payers agreed – Pratik Choudhary and I continue to have discussions with payers on the basis of the NICE recommendations,” said Dr Wilmot.
Since 2008, NICE has recommended insulin pumps for all people with type 1 diabetes who have an HbA1c of more than 8.5% (69 mmol/mol) or disabling hypoglycaemia, but fewer than one in five of those eligible in England has a pump.
Meanwhile, Partha Kar, Director of Type 1 Diabetes at NHS England, is driving access to HCL in England and put together an HCL pilot scheme that was launched in summer 2021. This is open to those on a pump, using is-CGM and with HbA1c more than 8.5% (69 mmol/mol). “At the same time, Pratik, Tom Crabtree and I put together the ABCD DTN-UK [Association of British Clinical Diabetologists Diabetes Technology Network] HCL audit, which collects anonymised data from users to explore the efficacy and safety of commercial HCL systems,” said Dr Wilmot.
The audit was a pragmatic observational study of people in the HCL pilot project in 31 secondary adult diabetes services in the UK. There were 634 participants and the outcome measures are HbA1c, CGM metrics, diabetes distress, Gold awareness of hypoglycaemia scores (a score of between one and seven to assess how well a person can detect the onset of hypoglycaemia; one being always and seven being never), acute events and user opinion. Data is currently being reviewed but already shows reduced HbA1c, improved TIR and TBR, reduced diabetes distress and positive user feedback.
“In England, things are moving forward in terms of access to HCL,” said Dr Wilmot. “We are delighted to see NICE recommending wider access.” Draft Technical Appraisal recommendations on HCL were published in January and are out for consultation. Hybrid closed loop is recommended for people with type 1 diabetes with an HbA1c of 8% (64 mmol/mol) or more, despite optimal management with a pump, is-CGM or rt-CGM and also those who are pregnant or planning a pregnancy. “This means access for thousands and thousands of individuals,” she added, “but the key caveat is whether a cost-effective price can be agreed with NHS England.”
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.