Continuous subcutaneous insulin infusion versus multiple daily injection regimens in children and young people at diagnosis of type 1 diabetes: pragmatic randomised controlled trial and economic evaluation.

To compare the efficacy, safety, and cost utility of continuous subcutaneous insulin infusion (CSII) with multiple daily injection (MDI) regimens during the first year following diagnosis of type 1 diabetes in children and young people. Pragmatic, multicentre, open label, parallel group, randomised controlled trial and economic evaluation. 15 paediatric National Health Service (NHS) diabetes services in England and Wales. The study opened to recruitment in May 2011 and closed in January 2017. Patients aged between 7 months and 15 years, with a new diagnosis of type 1 diabetes were eligible to participate. Patients who had a sibling with the disease, and those who took drug treatments or had additional diagnoses that could have affected glycaemic control were ineligible. Participants were randomised, stratified by age and treating centre, to start treatment with CSII or MDI within 14 days of diagnosis. Starting doses of aspart (CSII and MDI) and glargine or detemir (MDI) were calculated according to weight and age, and titrated according to blood glucose measurements and according to local clinical practice. Primary outcome was glycaemic control (as measured by glycated haemoglobin; HbA1c) at 12 months. Secondary outcomes were percentage of patients in each treatment arm with HbA1c within the national target range, incidence of severe hypoglycaemia and diabetic ketoacidosis, change in height and body mass index (as measured by standard deviation scores), insulin requirements (units/kg/day), partial remission rate (insulin dose adjusted HbA1c <9), paediatric quality of life inventory score, and cost utility based on the incremental cost per quality adjusted life year (QALY) gained from an NHS costing perspective. 294 participants were randomised and 293 included in intention to treat analyses (CSI, n=144; MDI, n=149). At 12 months, mean HbA1c was comparable with clinically unimportant differences between CSII and MDI participants (60.9 mmol/mol v 58.5 mmol/mol, mean difference 2.4 mmol/mol (95% confidence interval -0.4 to 5.3), P=0.09). Achievement of HbA1c lower than 58 mmol/mol was low among the two groups (66/143 (46%) CSII participants v 78/142 (55%) MDI participants; relative risk 0.84 (95% confidence interval 0.67 to 1.06)). Incidence of severe hypoglycaemia and diabetic ketoacidosis were low in both groups. Fifty four non-serious and 14 serious adverse events were reported during CSII treatment, and 17 non-serious and eight serious adverse events during MDI treatment. Parents (but not children) reported superior PedsQL scores for those patients treated with CSII compared to those treated with MDI. CSII was more expensive than MDI by £1863 (€2179; $2474; 95% confidence interval £1620 to £2137) per patient, with no additional QALY gains (difference -0.006 (95% confidence interval -0.031 to 0.018)). During the first year following type 1 diabetes diagnosis, no clinical benefit of CSII over MDI was identified in children and young people in the UK setting, and treatment with either regimen was suboptimal in achieving HbA1c thresholds. CSII was not cost effective. Current Controlled Trials ISRCTN29255275; European Clinical Trials Database 2010-023792-25.

Blair JC ，McKay A ，Ridyard C ，Thornborough K ，Bedson E ，Peak M ，Didi M ，Annan F ，Gregory JW ，Hughes DA ，Gamble C ，SCIPI investigators ... -  《BMJ-British Medical Journal》

Continuous subcutaneous insulin infusion versus multiple daily injections in children and young people at diagnosis of type 1 diabetes: the SCIPI RCT.

Blair J ，McKay A ，Ridyard C ，Thornborough K ，Bedson E ，Peak M ，Didi M ，Annan F ，Gregory JW ，Hughes D ，Gamble C ... -  《-》

A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.

Heller S ，White D ，Lee E ，Lawton J ，Pollard D ，Waugh N ，Amiel S ，Barnard K ，Beckwith A ，Brennan A ，Campbell M ，Cooper C ，Dimairo M ，Dixon S ，Elliott J ，Evans M ，Green F ，Hackney G ，Hammond P ，Hallowell N ，Jaap A ，Kennon B ，Kirkham J ，Lindsay R ，Mansell P ，Papaioannou D ，Rankin D ，Royle P ，Smithson WH ，Taylor C ... -  《-》

Effect of initiating use of an insulin pump in adults with type 1 diabetes using multiple daily insulin injections and continuous glucose monitoring (DIAMOND): a multicentre, randomised controlled trial.

The benefit of initiation of insulin pump therapy (continuous subcutaneous insulin infusion; CSII) in patients with type 1 diabetes using continuous glucose monitoring (CGM) has not been studied. We aimed to assess glycaemic outcomes when switching from multiple daily injections (MDI) to CSII in adults with type 1 diabetes using CGM. In this multicentre, randomised controlled trial, 75 adults with type 1 diabetes in the CGM group of the DIAMOND trial were randomly assigned via the study website using a computer-generated sequence to continue MDI or switch to CSII, with continuation of CGM, for 28 weeks. The primary outcome was CGM-measured time in the glucose concentration range of 70-180 mg/dL (3·9-10·0 mmol/L). This study is registered with ClinicalTrials.gov, number NCT02282397. Between April 14, 2015, and May 5, 2016, 37 participants were randomly assigned to the CGM plus CSII group and 38 participants were randomly assigned to the CGM plus MDI group. The study was completed by 36 (97%) of 37 participants in the CGM plus CSII group and 35 (92%) of 38 participants in the CGM plus MDI group. Mean CGM use was 6·7 days per week (SD 0·8) in the CGM plus CSII group and 6·9 days per week (0·3) in the CGM plus MDI group (p=0·86). No participants in the CGM plus CSII group who completed the trial discontinued CSII. Over the follow-up period, mean time in the glucose concentration range of 70-180 mg/dL (3·9-10·0 mmol/L) was 791 min per day (SD 157) in the CGM plus CSII group and 741 min per day (225) in the CGM plus MDI group (adjusted mean treatment group difference: 83 min, 95% CI 17-149; p=0·01). Participants in the CGM plus CSII group had a greater reduction in CGM-measured mean glucose (p=0·005) and hyperglycaemia (on four metrics: p=0·007 for >180 mg/dL [>10·0 mmol/L], p=0·02 for >250 mg/dL [>13·9 mmol/L], p=0·04 for >300 mg/dL [>16·6 mmol/L], and p=0·02 for the area under the curve for 180 mg/dL [10·0 mmol/L]), but also an increase in CGM-measured hypoglycaemia (p=0·0001 for <70 mg/dL [<3·9 mmol/L], p=0·0002 for <60 mg/dL [<3·3 mmol/L], p=0·0009 for <50 mg/dL [<2·8 mmol/L], p=0·0002 for the area over the curve for 70 mg/dL [3·9 mmol/L]). Mean HbA1c change from baseline to 28 weeks was 0·3% (SD 0·9; 3·3 mmol/mol [SD 9·8]) in the CGM plus CSII group and 0·1% (0·4; 1·1 mmol/mol [4·4]) in the CGM plus MDI group (p=0·32). Severe hypoglycaemia occurred in one participant in the CGM plus MDI group, and diabetic ketoacidosis and severe hyperglycaemia occurred in one participant each in the CGM plus CSII group. Our findings show that glycaemic control measured by time in the glucose range of 70-180 mg/dL (3·9-10·0 mmol/L) is improved by initiation of CSII in adults with type 1 diabetes. However, biochemical hypoglycaemia also was increased in the study, which will be important to consider when incorporating these results into clinical practice. Dexcom.

Beck RW ，Riddlesworth TD ，Ruedy KJ ，Kollman C ，Ahmann AJ ，Bergenstal RM ，Bhargava A ，Bode BW ，Haller S ，Kruger DF ，McGill JB ，Polonsky W ，Price D ，Toschi E ，DIAMOND Study Group ... -  《-》

Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic evaluation.

Cummins E ，Royle P ，Snaith A ，Greene A ，Robertson L ，McIntyre L ，Waugh N ... -  《-》