Elsevier

The Lancet

Volume 384, Issue 9950, 4–10 October 2014, Pages 1265-1272
The Lancet

Articles
Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial

https://doi.org/10.1016/S0140-6736(14)61037-0Get rights and content

Summary

Background

Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise).

Methods

We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8·0–12·0% (64–108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0·75 and size 4 with probability 0·25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01182493.

Findings

495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1·1% (SD 1·2; 12 mmol/mol, SD 13) in the pump treatment group and 0·4% (SD 1·1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of −0·7% (95% CI −0·9 to −0·4; −8 mmol/mol, 95% CI −10 to −4, p<0·0001). At the end of the study, the mean total daily insulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (p<0·0001), with no significant difference in bodyweight change between the two groups (1·5 kg [SD 3·5] vs 1·1 kg [3·6], p=0·322). Two diabetes-related serious adverse events (hyperglycaemia or ketosis without acidosis) resulting in hospital admission occurred in the pump treatment group compared with one in the multiple daily injection group. No ketoacidosis occurred in either group and one episode of severe hypoglycaemia occurred in the multiple daily injection group.

Interpretation

In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option.

Funding

Medtronic.

Introduction

Type 2 diabetes is characterised by insulin resistance and progressive β-cell failure, which results in increasing hyperglycaemia.1 Many patients with advanced disease require treatment with insulin, and in most cases the addition of basal insulin is sufficient to achieve glycated haemoglobin targets.2, 3 If these targets are not met after active dose titration of basal insulin, a multiple daily injection regimen combining a long-acting and a rapid-acting insulin in a basal-bolus fashion can be offered to patients; however, such intensified regimens do not meet glycated haemoglobin targets in about 30% of patients, and are associated with increased risks of hypoglycaemia and weight gain.4 These limitations of multiple daily injection treatment show the need for new treatments for this group of patients.

Only four randomised controlled studies have compared pump treatment and multiple daily injection treatment for lowering glycated haemoglobin in patients with type 2 diabetes. Two parallel-group studies5, 6 included 132 and 107 moderately obese, insulin-using patients with a baseline glycated haemoglobin of 8·0–8·4%. The studies lasted 6 months and 12 months respectively and reported similar benefit from treatment intensification. By contrast, two randomised crossover studies7, 8 showed that pump treatment was superior to multiple daily injections. Uncontrolled longitudinal studies9, 10 have also shown that pump treatment can help to achieve and maintain good metabolic control.

To further assess the potential benefits of pump treatment for type 2 diabetes, we did a randomised, controlled trial (OpT2mise) to compare the efficacy and safety of pump treatment and multiple daily injection treatment for patients with type 2 diabetes who had not responded to a basal-bolus regimen after active insulin titration.

Section snippets

Study design and participants

OpT2mise was a randomised, parallel-group study consisting of a run-in period, a 6-month randomised phase, and a 6-month continuation phase. 36 hospitals, tertiary care centres, and referal centres participated: eight in Canada, 23 in Europe and Israel, two in South Africa, and three in the USA. The study started in December 2010, and the final data collection date for the primary outcome measure was in February 2014. The study methods have been reported in full elsewhere.11 Only the results of

Results

Between Dec 26, 2010 to May 17, 2013, 590 patients were assessed for eligibility, of whom 495 entered the 2-month run-in phase. Of these, 164 were excluded (figure 1) and 331 entered the study phase and were randomly assigned to either the pump treatment group (n=168) or the multiple daily injection group (n=163). This small imbalance is a result of the random block sizes for each centre and also by the different number of patients recruited at each centre. Centres stopped recruitment when the

Discussion

In this large multinational study, we report that treatment with an insulin pump is better at reducing glycated haemoglobin than multiple daily injections in patients with type 2 diabetes. Previous studies5, 6, 7, 8, 9, 10, 16 of the efficacy of pump treatment for patients with type 2 diabetes enrolled few participants and yielded inconclusive results (panel). Only four randomised controlled studies comparing the ability of pump treatment and multiple daily injection treatment to lower blood

References (21)

  • E Ferrannini et al.

    Beta-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis

    J Clin Endocrinol Metab

    (2005)
  • DM Nathan et al.

    Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes

    Diabetologia

    (2009)
  • MC Riddle et al.

    The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients

    Diabetes Care

    (2003)
  • M Riddle et al.

    Contributions of basal and postprandial hyperglycaemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes

    Diabetes Care

    (2011)
  • P Raskin et al.

    Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study

    Diabetes Care

    (2003)
  • WH Herman et al.

    A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes

    Diabetes Care

    (2005)
  • E Berthe et al.

    Effectiveness of intensive insulin therapy by multiple daily injections and continuous subcutaneous infusion: a comparison study in type 2 diabetes with conventional insulin regimen failure

    Horm Metab Res

    (2007)
  • J Wainstein et al.

    Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patients

    Diabet Med

    (2005)
  • Y Reznik et al.

    Efficacy of continuous subcutaneous insulin infusion in type 2 diabetes mellitus: a survey on a cohort of 102 patients with prolonged follow-up

    Diabetes Technol Ther

    (2010)
  • J Kesavadev et al.

    Reduction of glycosylated haemoglobin following 6 months of continuous subcutaneous insulin infusion in an Indian population with type 2 diabetes

    Diabetes Technol Ther

    (2009)
There are more references available in the full text version of this article.

Cited by (0)

View full text