Clinical and technical evidence
A literature search was carried out for this briefing in accordance with NICE's interim process and methods statement for the production of medtech innovation briefings. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting email@example.com.
There are 6 studies summarised in this briefing, including 4 randomised controlled trials, 1 randomised cross over study and 1 retrospective study. In total, there were 6,622 people included in these studies.
The studies included have appropriate sample sizes and present relevant outcome measures. Some of the studies evaluate long-term outcomes, but 2 studies are limited by a short study period. Using multiple insulin pumps as comparators could make comparisons with the device more difficult. All studies were done in the US and so the evidence may not generalisable to the NHS.
Intervention: closed-loop system comprised of a t:slim X2 insulin pump with Control‑IQ and a Dexcom G6 continuous glucose monitor (CGM).
Comparator: sensor-augmented pump (t:slim X2 insulin pump without Control‑IQ in patients new to insulin pump use) and a CGM.
The percentage of time glucose levels were within the target range increased from 61% (plus or minus 17%) at baseline to 71% (plus or minus 12%) in the closed-loop group but remained unchanged in the control group (59%, plus or minus 14%). There were lower glycated haemoglobin levels at 26 weeks in the closed-loop group than the control group (mean difference -0.33%; 95% confidence interval [CI], -0.53 to -0.13; p=0.001). There were 17 adverse events reported (including 1 instance of diabetic ketoacidosis) in the closed-loop group compared with 2 in the control group (p=0.05).
The study randomised people in a 2:1 ratio to the closed-loop and control group, respectively. Both groups had similar patient demographics and baseline blood glucose control. No exclusions were made based on glycated haemoglobin level. There were also 100% of people who stayed in the study for the whole duration, and a high level of adherence to the assigned devices in both groups.
Randomised controlled multicentre trial of 109 people with type 1 diabetes (aged 14 to 72) over 3 months in the US. This is an extension study to Brown et al. (2019).
Intervention: closed-loop system comprised of a t:slim X2 insulin pump with Control‑IQ and a Dexcom G6 CGM.
Comparator: predictive low-glucose suspend system comprised of a sensor-augmented pump and a CGM.
People who continued to use the closed-loop system from the first trial could maintain time in range (70 to 180 mg/dl) for this 3‑month extension period (71.1% plus or minus 11.2% at baseline and 67.6% plus or minus 12.6% after the extension period; baseline measurements calculated as the last 13 weeks of the initial trial). This is compared with the control group, which went from 70.0% plus or minus 13.6% at baseline to 60.4% plus or minus 17.1% at the end of the extension period. HbA1c at the end of this study was lower in the intervention than the control group (7.2% compared with 7.5%; p=0.0035).
There was no remote monitoring and only 1 clinic visit in this study to reflect real-world device usage. Because this was an extension study, the device users were more familiar with the technology potentially leading to better glucose control. Control-IQ was suspended for 4 weeks during this study.
Intervention: closed-loop system comprised of a t:slim X2 insulin pump with Control‑IQ and a Dexcom G6 CGM as well as a Dexcom G5 CGM (because remote monitoring for Dexcom G6 was not yet available).
Comparator: sensor-augmented pump (user's own) and a Dexcom G5 CGM.
In the 3 days of home device usage, time in target blood glucose range (70 mg/dl to 180 mg/dl) was improved in the closed-loop group compared with the control (closed loop: 71.0% plus or minus 6.6%; control: 52.8% plus or minus 13.5%; p=0.001). The mean glucose was 152.2 mg/dl (plus or minus 13.8 mg/dl) in the closed-loop group compared with 180.2 mg/dl (plus or minus 23.1 mg/dl; p=0.003) in the control. There was a reduction in hyperglycaemia exposure in the closed-loop group compared with the control group and no differences in hypoglycaemia exposure. A survey of device usability found that the closed-loop system was viewed favourably by the users.
Multicentre 6-week randomised crossover trial of 103 people with type 1 diabetes in the US. The trial consisted of 2 × 3‑week periods when people were randomly assigned to use the predictive low‑glucose version of the pump during 1 period and the non-predictive low‑glucose version during the other.
Intervention: closed-loop system comprised of t:slim X2 pump with Basal‑IQ integrated with a Dexcom G5 sensor and predictive low‑glucose suspend technology.
Mean time in range (70 mg/dl to 180 mg/dl) increased in the intervention arm compared with the control arm (64% at baseline, 65% with intervention, and 63% with control; p<0.001). There was a reduction of time in hypoglycaemia (p<0.001) in the intervention arm compared with comparator. No one in the trial experienced severe hypoglycaemia or diabetic ketoacidosis during the intervention period. There was 1 severe hypoglycaemic event reported in the control period. A system usability survey stated that people would like to continue using the device with predictive low-glucose functionality and stated that it was straightforward to use.
Closed-loop system comprised of t:slim X2 pump with a compatible CGM before and after using Basal‑IQ with the predictive low-glucose suspend system.
Time in range (70 mg/dl to 180 mg/dl) increased from 57.8% to 58.5% (0.64, 95% CI 0.04 to 1.24; p<0.001) and time in which blood glucose was less than 70 mg/dl decreased from 2.14% to 1.18% (-1.01, 95% CI -0.97 to -1.05; p<0.001) after installation of the Basal‑IQ software. Of the 1,301 subjects in which 9 months of follow-up data was available, time in which blood glucose was less than 70 mg/dl remained at 1.2% and time in range was 62.6% (plus or minus 16.6%).
Intervention: closed-loop system comprised of a t:slim X2 insulin pump with Control‑IQ and both a Dexcom G6 and G5 CGM.
Comparator: sensor-augmented pumps with low‑glucose suspend technologies deactivated and a Dexcom G5 CGM.
The Control‑IQ system led to a 12% increase in time in range (70 mg/dl to 180 mg/dl) from 53.9% (plus or minus 24.8%) in the control group to 66.4% (plus or minus 16.4%) in the Control‑IQ group (p=0.01). There was a 15% reduction of time spent in hyperglycaemia (above 180 mg/dl) in Control‑IQ group compared with the control group (31.4%, plus or minus 17.6%, compared with 43%, plus or minus 24.5%; p=0.015). There was no difference in the time in hypoglycaemia or the amount of carbohydrate treatments for hypoglycaemia between the groups. There were no adverse events in either group.
This randomised controlled trial, although only done over 48 hours, studied the efficacy of the pumps with prolonged intense activity. Remote monitoring by clinicians could have led to improved glycaemic control compared with real-world usage. The study was partially funded by the company.
The company claims the technology will reduce environmental impact with use of a rechargeable battery for the pump, which can last up to 7 days. It can also be charged without interrupting insulin delivery using existing or supplied mini USB cables. There is no published evidence to support these claims.
AIDE T1D RCT: automated insulin delivery in the elderly with type 1 diabetes. ClinicalTrials.gov identifier: NCT04016662. Status: not yet recruiting. Indication: type 1 diabetes. Devices: Tandem t:slim X2 with HCL or PLGS features. Date: April 2022. Country: US.
AIR-CGM RCT: assessment of the impact of real-time continuous glucose monitoring in people presenting with severe hypoglycaemia. ClinicalTrials.gov identifier: NCT03748433. Status: active, not recruiting. Indication: type 1 diabetes, hypoglycaemia unawareness, hypoglycaemia. Devices: Dexcom G6 CGM, Tandem t:slim X2 Insulin Pump. Date: September 2020. Country: UK.