Background:

Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment.

Objective:

To assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy.

Design:

Pragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI.

Setting:

Eight secondary care diabetes centres in the UK.

Participants:

Adults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps.

Interventions:

Pump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm^® Veo^TM (Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK).

Main outcome measures:

Primary outcome – change in glycated haemoglobin (HbA_1c) at 2 years in participants whose baseline HbA_1c was ≥ 7.5% (58 mmol/mol). Key secondary outcome – proportion of participants with HbA_1c ≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months – moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness.

Results:

We randomised 46 courses comprising 317 participants: 267 attended a Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline HbA_1c of ≥ 7.5%. HbA_1c and severe hypoglycaemia improved in both groups. The drop in HbA_1c% at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference (MD) in HbA_1c change at 2 years, at which the baseline HbA_1c was ≥ 7.5%, was –0.24% [95% confidence interval (CI) –0.53% to 0.05%] in favour of the pump (p = 0.098). The per-protocol analysis showed a MD in change of –0.36% (95% CI –0.64% to –0.07%) favouring pumps (p = 0.015). Pumps were not cost-effective in the base case and all of the sensitivity analyses. The pump group had greater improvement in diabetes-specific QoL diet restrictions, daily hassle plus treatment satisfaction, statistically significant at 12 and 24 months and supported by qualitative interviews.

Limitation:

Blinding of pump therapy was not possible, although an objective primary outcome was used.

Conclusion:

Adding pump therapy to structured training in flexible insulin therapy did not significantly enhance glycaemic control or psychosocial outcomes in adults with T1DM.

Research priority:

To understand why few patients achieve a HbA_1c of < 7.5%, particularly as glycaemic control is worse in the UK than in other European countries.

Trial registration:

Current Controlled Trials ISRCTN61215213.

Funding:

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 20. See the NIHR Journals Library website for further project information.

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 08/107/01. The contractual start date was in June 2011. The draft report began editorial review in March 2016 and was accepted for publication in July 2016. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

The insulin pumps were provided free of charge and unconditionally by Medtronic, which had no involvement in the design of the protocol; the collection, analysis and interpretation of the data; the writing of this report; or the decision to submit the report for publication. Simon Heller is a Health Technology Assessment Clinical Evaluation and Trials Board Member, who reports personal fees from Sanofi-Aventis, and personal fees and other from Novo Nordisk and Eli Lilly, outside the submitted work. Katharine Barnard reports personal fees from Roche Diabetes Care, outside the submitted work. Michael Campbell was a National Institute for Health Research Health Services and Delivery Research Board Member from 2010 to 2014. Jackie Elliott reports personal fees from AstraZeneca, Merck Sharpe & Dohme and Takeda, and personal fees and non-financial support from Eli Lilly, Novo Nordisk and Sanofi-Aventis, outside the submitted work. Mark Evans reports personal fees and other from Abbott Diabetes Care, Medtronic, Roche, Eli Lilly, Novo Nordisk and Cellnovo, and grants from Senseonics and Oxford Medical Diagnostics, outside the submitted work. Peter Hammond reports personal fees from Medtronic, Johnson & Johnson, Roche, Novo Nordisk and Eli Lilly, outside the submitted work. Alan Jaap reports personal fees and non-financial support from Novo Nordisk, and personal fees from Eli Lilly, Takeda, Merck Sharpe & Dohme and AstraZeneca, outside the submitted work.