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The Lancet Journal

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

      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.
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      References

      1. 1.
        • Ferrannini E
        • Gastaldelli A
        • Miyazaki Y
        • Matsuda M
        • Mari A
        • DeFronzo RA
        Beta-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis.
        J Clin Endocrinol Metab. 2005; 90: 493-500
      2. 2.
        • Nathan DM
        • Buse JB
        • Davidson MB
        • 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; 52: 17-30
      3. 3.
        • Riddle MC
        • Rosenstock J
        • Gerich J
        • 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; 26: 3080-3086
      4. 4.
        • Riddle M
        • Umpierrez G
        • DiGenio A
        • 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; 34: 2508-2514
      5. 5.
        • Raskin P
        • Bode BW
        • Marks JB
        • 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; 26: 2598-2603
      6. 6.
        • Herman WH
        • Ilag LL
        • Johnson SL
        • et al.
        A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes.
        Diabetes Care. 2005; 28: 1568-1573
      7. 7.
        • Berthe E
        • Lireux B
        • Coffin C
        • 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; 39: 224-229
      8. 8.
        • Wainstein J
        • Metzger M
        • Boaz M
        • et al.
        Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patients.
        Diabet Med. 2005; 22: 1037-1046
      9. 9.
        • Reznik Y
        • Morera J
        • Rod A
        • 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; 12: 931-936
      10. 10.
        • Kesavadev J
        • Balakrishnan S
        • Ahammed S
        • 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; 11: 517-521
      11. 11.
        • Aronson R
        • Cohen O
        • Conget I
        • et al.
        OpT2mise: A randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes.
        Diabetes Technol Ther. 2014; (published online April 15.)https://doi.org/10.1089/dia.2013.0363
      12. 12.
        • Nasreddine ZS
        • Phillips NA
        • Bédirian V
        • et al.
        The Montreal Cognitive Assessment (MoCA): a brief screening tool for mild cognitive impairment.
        J Am Geriatr Soc. 2005; 53: 695-699
      13. 13.
        • O'Brien PC
        • Fleming TR
        A multiple testing procedure for clinical trials.
        Biometrics. 1979; 35: 549-556
      14. 14.
        • Rubin DB
        Multiple imputation for nonresponse in surveys. John Wiley & Sons, New York1987
      15. 15.
        • Chen YH
        • DeMets DL
        • Lan KK
        Increasing the sample size when the unblinded interim result is promising.
        Stat Med. 2004; 23: 1023-1038
      16. 16.
        • Edelman SV
        • Bode BW
        • Bailey TS
        • et al.
        Insulin pump therapy in patients with type 2 diabetes safely improved glycemic control using a simple insulin dosing regimen.
        Diabetes Technol Ther. 2010; 12: 627-633
      17. 17.
        • Fatourechi MM
        • Kudva YC
        • Murad MH
        • Elamin MB
        • Tabini CC
        • Montori VM
        Clinical review: Hypoglycaemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections.
        J Clin Endocrinol Metab. 2009; 94: 729-740
      18. 18.
        • Reznik Y
        • Cohen O
        Insulin pump for type 2 diabetes: Use and misuse of continuous subcutaneous insulin infusion in type 2 diabetes.
        Diabetes Care. 2013; 36: S219-S225
      19. 19.
        • Pouwels MJ
        • Tack CJ
        • Hermust AR
        • Lutterman JA
        Treatment with intravenous insulin followed by continuous subcutaneous insulin infusion improves glycaemic control in severely resistant type 2 diabetic patients.
        Diabet Med. 2003; 20: 76-79
      20. 20.
        • Wulffelé MG
        • Kooy A
        • Lehert P
        • et al.
        Combination of insulin and metformin in the treatment of type 2 diabetes.
        Diabetes Care. 2002; 12: 2133-2140
      21. 21.
        • Kooy A
        • de Jager J
        • Lehert P
        • et al.
        Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus.
        Arch Intern Med. 2009; 169: 616-625

      Linked Articles

      • Continuous subcutaneous insulin infusion for type 2 diabetes
        • With the dual onslaught of progressive β-cell failure and insulin resistance, many patients with diabetes struggle to achieve adequate glucose control despite escalation of treatment, including insulin.1 More than a third of patients who start basal insulin need more than 60 units per day to achieve target control2 but, at these doses, insulin absorption is slow and bioavailability is reduced.3 As endogenous insulin production decreases, the risk of hypoglycaemia increases,4 compounding difficulties in achieving glycaemic targets.
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