Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)

Abstract

Objective To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment.Design Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial).Setting Eight secondary care centres in England and Scotland.Participants Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment ("dose adjustment for normal eating," DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections.Interventions Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years.Main outcome measures The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction.Results 317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was -0.24% (-2.7 mmol/mol) in favour of pump users (95% confidence interval -0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24 months.Conclusions Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. Adding pump treatment to structured training in flexible intensive insulin treatment did not substantially enhance educational benefits on glycaemic control, hypoglycaemia, or psychosocial outcomes in adults with type 1 diabetes. These results do not support a policy of providing insulin pumps to adults with poor glycaemic control until the effects of training on participants' level of engagement in intensive self management have been determined.Trial registration Current Controlled Trials ISRCTN61215213.

Conflict of interest statement

Competing interests: All members of the writing committee have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: grant funding from the UK Health Technology Assessment Programme and financial support from Medtronic UK, for the submitted work; PC reports personal fees and non-financial support from Medtronic UK and personal fees from Roche, outside the submitted work. JE reports personal fees from Astra Zeneca, Eli Lily, Merck Sharpe Dohme, Novo Nordisk, Sanofi Aventis, and Takeda, and non-financial support from Eli Lilly, Novo Nordisk, and Sanofi, outside the submitted work. PH reports personal fees from Medtronic UK, Johnson and Johnson, Roche, Novo Nordisk, and Lilly, outside the submitted work. RL reports personal fees from Eli Lilly and Novo Nordisk, outside the submitted work. SH reports grants from Medtronic UK during the conduct of the study, and personal fees from Sanofi Aventis, Eli Lilly, Takeda, NovoNordisk, and Astra Zeneca, outside of the submitted work. His institution has received remuneration from Eli Lilly, Boeringher Ingelheim, NovoNordisk, Eli Lilly, and Takeda, outside the submitted work; he is currently chief investigator on an NIHR programme grant for applied research: RP-PG-0514-20013, the purpose of which is to develop more effective training programmes to improve self management of type 1 diabetes; no other relationships or activities that could appear to have influenced the submitted work.

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Figures

Fig 1 CONSORT flowchart for REPOSE cluster randomised trial to compare the effectiveness of insulin pumps with multiple daily injections (MDI). DAFNE=dose adjustment for normal eating

Fig 2 Mean change (%) in glycated haemoglobin (HbA1c) over time in participants with baseline HbA1c ≥7.5% (58 mmol/mol) (including only participants with data at all four time points, n=208). MDI=multiple daily injections

Fig 3 Mean difference in HbA1c change (%) at 24 months for pump versus multiple daily injections by subgroup. MCID=minimal clinically important difference; IMD=index of multiple deprivation; ONS=Office for National Statistics occupational status from level 1, elementary trade, service, administration roles, to level 4, corporate managers or directors, research, teaching, business, and public service higher level professionals

Fig 4 Mean difference in HbA1c change (%) at 24 months by subgroup