, Volume 55, Issue 1, pp 77–84

Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis

  • Khalid Benkhadra
  • Fares Alahdab
  • Shrikant U. Tamhane
  • Rozalina G. McCoy
  • Larry J. Prokop
  • Mohammad Hassan Murad


The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear. We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin, hypoglycemic events, and time spent in hypoglycemia compared to multiple daily injections. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus from January 2008 through November 2015 for randomized controlled trials that enrolled children or adults with type 1 diabetes. Trials identified in a previous systematic review and published prior to 2008 were also included. We included 25 randomized controlled trials at moderate risk of bias. Meta-analysis showed a significant reduction in glycosylated hemoglobin in patients treated with continuous subcutaneous insulin infusion compared to multiple daily injections (mean difference 0.37; 95 % confidence interval, 0.24–0.51). This effect was demonstrated in both children and adults. There was no significant difference in minor or severe hypoglycemic events. Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia. There was no significant difference in the time spent in hypoglycemia. In children and adults with type 1 diabetes and compared to multiple daily injections, continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin. There was no difference in severe or minor hypoglycemia, but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion.


Continuous subcutaneous infusion Diabetes Insulin Multiple daily injections Systematic review Diabetes mellitus type 1 

Supplementary material

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  1. 1.
    J.C. Pickup, H. Keen, J.A. Parsons, K.G. Alberti, Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. Br. Med. J. 1(6107), 204–207 (1978)CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    M.M. Fatourechi, Y.C. Kudva, M.H. Murad, M.B. Elamin, C.C. Tabini, V.M. Montori, 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(3), 729–740 (2009)CrossRefPubMedGoogle Scholar
  3. 3.
    S. Schmidt, New technologies in the treatment of type 1 diabetes. Dan. Med. J. 60(11), B4746 (2013)PubMedGoogle Scholar
  4. 4.
    E.G. Moser, A.A. Morris, S.K. Garg, Emerging diabetes therapies and technologies. Diabetes Res. Clin. Pract. 97(1), 16–26 (2012)CrossRefPubMedGoogle Scholar
  5. 5.
    D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman, P. Group, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int. J. Surg. 8(5), 336–341 (2010)CrossRefPubMedGoogle Scholar
  6. 6.
    J.P. Higgins, D.G. Altman, P.C. Gotzsche, P. Juni, D. Moher, A.D. Oxman et al., The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343, d5928 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    M.H. Murad, V.M. Montori, J.P. Ioannidis, R. Jaeschke, P.J. Devereaux, K. Prasad et al., How to read a systematic review and meta-analysis and apply the results to patient care: users’ guides to the medical literature. JAMA 312(2), 171–179 (2014)CrossRefPubMedGoogle Scholar
  8. 8.
    B.A. Swiglo, M.H. Murad, H.J. Schunemann, R. Kunz, R.A. Vigersky, G.H. Guyatt et al., A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. J. Clin. Endocrinol. Metab. 93(3), 666–673 (2008)CrossRefPubMedGoogle Scholar
  9. 9.
    D. Cohen, N. Weintrob, H. Benzaquen, A. Galatzer, G. Fayman, M. Phillip, Continuous subcutaneous insulin infusion versus multiple daily injections in adolescents with type I diabetes mellitus: a randomized open crossover trial. J. Pediatr. Endocrinol. Metab. 16(7), 1047–1050 (2003)CrossRefPubMedGoogle Scholar
  10. 10.
    S.A. Little, L. Leelarathna, E. Walkinshaw, H.K. Tan, O. Chapple, A. Lubina-Solomon et al., Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a multicenter 2 × 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS). Diabetes Care 37(8), 2114–2122 (2014)CrossRefPubMedGoogle Scholar
  11. 11.
    D. Bruttomesso, D. Crazzolara, A. Maran, S. Costa, M. Dal Pos, A. Girelli et al., In type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine. Diabet. Med. 25(3), 326–332 (2008)CrossRefPubMedGoogle Scholar
  12. 12.
    K.M. Thrailkill, C.S. Moreau, C. Swearingen, M. Rettiganti, K. Edwards, A.E. Morales et al., Insulin pump therapy started at the time of diagnosis: effects on glycemic control and pancreatic beta-cell function in type 1 diabetes. Diabetes Technol. Ther. 13(10), 1023–1030 (2011)CrossRefPubMedGoogle Scholar
  13. 13.
    R. Nuboer, G.J. Borsboom, J.A. Zoethout, H.M. Koot, J. Bruining, Effects of insulin pump vs. injection treatment on quality of life and impact of disease in children with type 1 diabetes mellitus in a randomized, prospective comparison. Pediatr. Diabetes 9(4 Pt 1), 291–296 (2008)CrossRefPubMedGoogle Scholar
  14. 14.
    R.P. Hoogma, P.J. Hammond, R. Gomis, D. Kerr, D. Bruttomesso, K.P. Bouter et al., Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial. Diabet. Med. 23(2), 141–147 (2006)CrossRefPubMedGoogle Scholar
  15. 15.
    M.I. Maiorino, G. Bellastella, M. Petrizzo, M.R. Improta, C. Brancario, F. Castaldo et al., Treatment satisfaction and glycemic control in young type 1 diabetic patients in transition from pediatric health care: CSII versus MDI. Endocrine 46(2), 256–262 (2014)CrossRefPubMedGoogle Scholar
  16. 16.
    M.I. Maiorino, O. Casciano, E.D. Volpe, G. Bellastella, D. Giugliano, K. Esposito, Reducing glucose variability with continuous subcutaneous insulin infusion increases endothelial progenitor cells in type 1 diabetes: an observational study. Endocrine 52(2), 244–252 (2016)CrossRefPubMedGoogle Scholar
  17. 17.
    E. Pankowska, M. Blazik, P. Dziechciarz, A. Szypowska, H. Szajewska, Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials. Pediatric Diabetes 10(1), 52–58 (2009)CrossRefPubMedGoogle Scholar
  18. 18.
    A. Nicolucci, A. Maione, M. Franciosi, R. Amoretti, E. Busetto, F. Capani et al., Quality of life and treatment satisfaction in adults with type 1 diabetes: a comparison between continuous subcutaneous insulin infusion and multiple daily injections. Diabetic Med. 25(2), 213–220 (2008)CrossRefPubMedGoogle Scholar
  19. 19.
    L. Opipari-Arrigan, E.M. Fredericks, N. Burkhart, L. Dale, M. Hodge, C. Foster, Continuous subcutaneous insulin infusion benefits quality of life in preschool-age children with type 1 diabetes mellitus. Pediatric Diabetes 8(6), 377–383 (2007)CrossRefPubMedGoogle Scholar
  20. 20.
    K.D. Barnard, C.E. Lloyd, T.C. Skinner, Systematic literature review: quality of life associated with insulin pump use in type 1 diabetes. Diabetic Med. 24(6), 607–617 (2007)CrossRefPubMedGoogle Scholar
  21. 21.
    J. Hermanides, K. Norgaard, D. Bruttomesso, C. Mathieu, A. Frid, C.M. Dayan et al., Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled type 1 diabetes; a randomized controlled trial. Diabet. Med. 28(10), 1158–1167 (2011)CrossRefPubMedGoogle Scholar
  22. 22.
    R.M. Bergenstal, W.V. Tamborlane, A. Ahmann, J.B. Buse, G. Dailey, S.N. Davis et al., Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N. Engl. J. Med. 363(4), 311–320 (2010)CrossRefPubMedGoogle Scholar
  23. 23.
    L.A. DiMeglio, T.M. Pottorff, S.R. Boyd, L. France, N. Fineberg, E.A. Eugster, A randomized, controlled study of insulin pump therapy in diabetic preschoolers. J. Pediatr. 145(3), 380–384 (2004)CrossRefPubMedGoogle Scholar
  24. 24.
    E.A. Doyle, S.A. Weinzimer, A.T. Steffen, J.A. Ahern, M. Vincent, W.V. Tamborlane, A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care 27(7), 1554–1558 (2004)CrossRefPubMedGoogle Scholar
  25. 25.
    L.A. Fox, L.M. Buckloh, S.D. Smith, T. Wysocki, N. Mauras, A randomized controlled trial of insulin pump therapy in young children with type 1 diabetes. Diabetes Care 28(6), 1277–1281 (2005)CrossRefPubMedGoogle Scholar
  26. 26.
    I.B. Hirsch, B.W. Bode, S. Garg, W.S. Lane, A. Sussman, P. Hu et al., Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII. Diabetes Care 28(3), 533–538 (2005)CrossRefPubMedGoogle Scholar
  27. 27.
    N. Weintrob, H. Benzaquen, A. Galatzer, S. Shalitin, L. Lazar, G. Fayman et al., Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens in children with type 1 diabetes: a randomized open crossover trial. Pediatrics 112(3 Pt 1), 559–564 (2003)CrossRefPubMedGoogle Scholar
  28. 28.
    N. Weintrob, A. Schechter, H. Benzaquen, S. Shalitin, P. Lilos, A. Galatzer et al., Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion. Arch. Pediatr. Adolesc. Med. 158(7), 677–684 (2004)CrossRefPubMedGoogle Scholar
  29. 29.
    D.M. Wilson, B.A. Buckingham, E.L. Kunselman, M.M. Sullivan, H.U. Paguntalan, S.E. Gitelman, A two-center randomized controlled feasibility trial of insulin pump therapy in young children with diabetes. Diabetes Care 28(1), 15–19 (2005)CrossRefPubMedGoogle Scholar
  30. 30.
    M. Peyrot, R.R. Rubin, Patient-reported outcomes for an integrated real-time continuous glucose monitoring/insulin pump system. Diabetes Technol. Ther. 11(1), 57–62 (2009)CrossRefPubMedGoogle Scholar
  31. 31.
    G.B. Bolli, D. Kerr, R. Thomas, E. Torlone, A. Sola-Gazagnes, E. Vitacolonna et al., Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study. Diabetes Care 32(7), 1170–1176 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    L. Skogsberg, H. Fors, R. Hanas, J.E. Chaplin, E. Lindman, J. Skogsberg, 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. Pediatric Diabetes 9(5), 472–479 (2008)CrossRefPubMedGoogle Scholar
  33. 33.
    I. Rabbone, A. Bobbio, V. Di Gianni, C. Sacchetti, F. Cerutti, Intensive insulin therapy in preschool-aged diabetic children: from multiple daily injections to continuous subcutaneous insulin infusion through indwelling catheters. J. Endocrinol. Invest. 31(3), 193–195 (2008)CrossRefPubMedGoogle Scholar
  34. 34.
    S. Rosenlund, T.W. Hansen, P. Rossing, S. Andersen, Effect of sensor-augmented pump treatment versus multiple daily injections on albuminuria: a 1-year randomized study. J. Clin. Endocrinol. Metab. 100(11), 4181–4188 (2015)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Khalid Benkhadra
    • 1
    • 2
  • Fares Alahdab
    • 2
  • Shrikant U. Tamhane
    • 3
  • Rozalina G. McCoy
    • 1
    • 4
  • Larry J. Prokop
    • 5
  • Mohammad Hassan Murad
    • 1
    • 2
  1. 1.Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo ClinicRochesterUSA
  2. 2.Division of Preventive, Occupational and Aerospace Medicine, Department of MedicineMayo ClinicRochesterUSA
  3. 3.Division of Endocrinology, Department of MedicineMayo ClinicRochesterUSA
  4. 4.Division of Primary Care Internal Medicine, Department of MedicineMayo ClinicRochesterUSA
  5. 5.Mayo Clinic LibrariesMayo ClinicRochesterUSA

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