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Continuous subcutaneous insulin infusion vs modern multiple injection regimens in type 1 diabetes: an updated meta-analysis of randomized clinical trials

  • Laura PalaEmail author
  • Ilaria Dicembrini
  • Edoardo Mannucci
Review Article
  • 99 Downloads

Abstract

Meta-analyses of clinical trials comparing CSII with traditional insulin injections usually show a small, but significant advantage of CSII with respect to HbA1c and risk of severe hypoglycemia. On the other hand, CSII is associated with a small, but relevant risk of ketoacidosis, mainly due to malfunction of insulin pump and/or catheter occlusion. During last time, the technology of insulin pumps and infusion sets has improved as the profound evolution in type and schemes with traditional insulin injections. Aim of the present study is to update previous meta-analyses comparing CSII with traditional insulin injections in subjects with type 1 diabetes. Specific subgroup analyses were designed for assessing the effects of CSII in comparison with basal-bolus MDI, with short-acting analogues as bolus and long-acting analogues as basal insulin. In addition, an exploratory analysis was performed to verify the effect of CSII in insulin-naïve patients with type 1 diabetes. The present analysis includes all randomized clinical trials comparing CSII with traditional injections in type 1 diabetes, with a duration of at least 12 weeks. Animal studies were excluded, whereas no language or date restriction was imposed. If duplicate publications of a single trial were present, the paper containing more adequate information was considered as principal publication. In trials comparing CSII with basal-bolus MDI, performed before the introduction of rapid-acting analogues, regular human insulin was used for CSII, and as prandial insulin in control groups. CSII was associated with a significant reduction of A1c, in comparison with MDI, irrespective of the use of either human insulin or rapid-acting analogues. However, in trials with rapid-acting analogue the advantage of CSII was significantly smaller than in trials with regular human insulin (HbA1c difference: − 0.29[− 0.46; − 0.13] vs − 1.93[− 1.84; − 0.42]%; p = 0.02). Different rapid-acting analogues provided similar results (HbA1c reduction vs MDI: − 0.25 [− 0.48; − 0.02]%, p = 0.03, and − 0.29 [− 0.49; − 0.09]%, p = 0.005, for lispro and aspart, respectively). In addition, in trials comparing CSII with basal-bolus MDI, CSII reduced HbA1c to a similar extent irrespective of the use of either NPH or long-acting analogues as basal insulin in the control groups (HbA1c reduction vs MDI: − 0.31 [− 0.55; − 0.06]%, p = 0.01, and − 0.20 [− 0.38; − 0.03]%, p = 0.02, for NPH and long-acting analogues, respectively. With respect to severe hypoglycemia, CSII did not produce a significant reduction of risk in comparison with traditional insulin injections. Conversely, CSII was associated with a significant increase in the incidence of reported diabetic ketoacidosis (DKA). Notably, the increased risk of DKA was significant in trials comparing CSII with conventional insulin therapy, whereas only a nonsignificant trend toward an increased risk was observed in comparisons with basal-bolus MDI. Only two trials comparing CSII with basal-bolus MDI, both using rapid-acting analogues, were performed on insulin-naïve type 1 diabetic patients. When those two trials were analyzed separately, CSII did not produce any relevant effect on HbA1c (difference from control: − 0.10[− 0.38; + 0.17]%; p = 0.46). No meta-analysis could be performed on either severe hypoglycemia or DKA, which were not reported by one of the two trials. CSII seems to produce a small improvement in HbA1c in patients with type 1 diabetes inadequately controlled with MDI. This apparent effect, which could be partly due to publication bias, is smaller when MDI is properly performed using basal-bolus schemes with short-acting insulin analogues. Other outcomes different from HbA1c (such as quality of life) could be relevant for the choice of CSII instead of MDI. In addition, further studies are needed to better define the profile of patients who could benefit most from CSII.

Keywords

Continuous subcutaneous insulin infusion (CSII) Continuous glucose monitoring (CGM) Flash glucose monitoring (FGM) Sensor-augmented pump (SAP) 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participant or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

592_2019_1326_MOESM1_ESM.docx (4.1 mb)
Supplementary material 1 (DOCX 4200 KB)

References

  1. 1.
    Pozzilli P, Battelino T, Danne T, Hovorka R, Jarosz-Chobot P, Renard E (2016) Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics. Diabetes Metab Res Rev 32(1):21–39CrossRefPubMedGoogle Scholar
  2. 2.
    Cummins E, Royle P, Snaith A, Greene A, Robertson L, McIntyre L, Waugh N (2010) Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic evaluation. Health Technol Assess 14(11):iii-iv (xi–xvi, 1–181)CrossRefGoogle Scholar
  3. 3.
    Pickup J, Mattock M, Kerry S (2002) Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomized controlled trials. BMJ 324(7339):705CrossRefPubMedGoogle Scholar
  4. 4.
    Jeitler K, Horvath K, Berghold A, Gratzer TW, Neeser K, Pieber TR, Siebenhofer A (2008) Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis. Diabetologia 51:941–951CrossRefPubMedGoogle Scholar
  5. 5.
    Misso ML, Egberts KJ, Page M, O’Connor D, Shaw J (2010) Continuous subcutaneous insulin infusion (CSII) versusmultiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev 20;(1):CD005103.  https://doi.org/10.1002/14651858.CD005103.pub2 Google Scholar
  6. 6.
    Yeh HC, Brown TT, Maruthur N, Ranasinghe P, Berger Z, Suh YD, Wilson LM, Haberl EB, Brick J, Bass EB, Golden SH (2012) Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med 157(5):336–347CrossRefPubMedGoogle Scholar
  7. 7.
    Pickup JC, Sutton AJ (2008) Severe hypoglycaemia and glycaemic control in type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med 25:765–774CrossRefPubMedGoogle Scholar
  8. 8.
    Jacobsen IB, Henriksen JE, HotherNielsen O, Vach W, Beck-Nielsen H (2009) Evidence-based insulin treatment in type 1 diabetes mellitus. Diabetes Res ClinPract 86:1–10CrossRefGoogle Scholar
  9. 9.
    Fatourechi MM, Kudva YC, Murad MH, Elamin MB, Tabini CC, Montori VM (2009) Clinical review: Hypoglycemia 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 94:729–740CrossRefPubMedGoogle Scholar
  10. 10.
    Farsani SF, Brodovicz K, Soleymanlou N, Marquard J, Wissinger E, Maiese BA (2017) Incidence and prevalence of diabetic ketoacidosis (DKA) among adults with type 1 diabetes mellitus (T1D): a systematic literature review. BMJ Open 7(7):e016587CrossRefGoogle Scholar
  11. 11.
    The Diabetes Control and Complications Trial Research Group (DCTT) (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRefGoogle Scholar
  12. 12.
    Siebenhofer A, Plank J, Berghold A, Jeitler K, Horvath K, Narath M, Gfrerer R, Pieber TR (2006) Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev Apr 19(2):CD003287Google Scholar
  13. 13.
    Jacobsen IB, Henriksen JE, Hother-Nielsen O, Vach W, Beck-Nielsen H (2009) Evidence-based insulin treatment in type 1 diabetes mellitus. Diabetes Res ClinPract 86(1):1–10CrossRefGoogle Scholar
  14. 14.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D(2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700CrossRefPubMedGoogle Scholar
  15. 15.
    Pozzilli P, Crinò A, Schiaffini R, Manfrini S, Fioriti E, Coppolino G, Pitocco D, Visalli N, Corbi S, Spera S, Suraci C, Cervoni M, Matteoli MC, Patera IP, Ghirlanda G, And The Imdiab Group (2003) A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8). Diabetes Technol Ther 5(6):965–974CrossRefPubMedGoogle Scholar
  16. 16.
    Skogsberg L, Fors H, Hanas R, Chaplin JE, Lindman E, Skogsberg J (2008) Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus. Pediatr Diabetes 9:472–479CrossRefPubMedGoogle Scholar
  17. 17.
    Amiel SA, Pursey N, Higgins B, Dawoud D, Guideline Development Group (2015) Diagnosis and management of type 1 diabetes in adults: summary of updated NICE guidance. BMJ  https://doi.org/10.1136/bmj.h4188 PubMedGoogle Scholar
  18. 18.
    McGibbon A, Adams L, Ingersoll K, Kader T, Tugwell B (2018) Glycemic management in adults with type 1 diabetes. Diabetes Canada Clinical Practice Guidelines Expert Committee. Can J Diabetes 42(Suppl1):S80–S87CrossRefPubMedGoogle Scholar
  19. 19.
    Updates to the Standards of Medical Care in Diabetes (2018) Association American Diabetes. Diabetes Care 41(9):2045–2047CrossRefGoogle Scholar
  20. 20.
    Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H (2009) Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ 180(4):385–397CrossRefPubMedGoogle Scholar
  21. 21.
    Laranjeira FO, de Andrade KRC, Figueiredo ACMG, Silva EN, Pereira MG (2018) Long-acting insulin analogues for type 1 diabetes: an overview of systematic reviews and meta-analysis of randomized controlled trials. PLoS One 13(4):e0194801CrossRefPubMedGoogle Scholar
  22. 22.
    Pickup JC (2012) Insulin-pump therapy for type 1 diabetes mellitus. N Engl J Med 366:1616–1624CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Laura Pala
    • 1
    Email author
  • Ilaria Dicembrini
    • 1
    • 2
  • Edoardo Mannucci
    • 1
    • 2
  1. 1.Department of DiabetologyCareggi HospitalFlorenceItaly
  2. 2.University of FlorenceFlorenceItaly

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