Skip to main content
SpringerLink
Log in

Insulin Management in Type 2 Diabetes

  • Chapter
  • First Online:
Handbook of Insulin Therapies

  • 1532 Accesses

Abstract

Type 2 diabetes mellitus (T2DM) is a progressive disease typically characterized by insulin resistance and diminishing β-cell reserve, eventually leading to insulin deficiency. In addition to insulin resistance within the muscle, liver, brain, and β cells, other pathogenic abnormalities include accelerated lipolysis within adipose tissue, gastrointestinal incretin deficiency/resistance, hyperglucagonemia, and abnormalities in renal glucose reabsorption and require a multifaceted approach to management [1]. From a clinical standpoint, this is reflected by initial management with lifestyle modification and treatment with metformin and addition of other classes of glucose-lowering therapies, including conventional agents, such as sulfonylureas (SUs), thiazolidinediones (TZDs), meglitinides, and newer therapies including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium–glucose co-transporter 2 (SGLT2) inhibitors to achieve satisfactory glycemic targets.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. DeFronzo RA. Banting Lecture: From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998;15:297–303.

    Article  CAS  PubMed  Google Scholar 

  3. Vora J. Combining incretin-based therapies with insulin: realizing the potential in type 2 diabetes. Diabetes Care. 2013;S226–32.

    Google Scholar 

  4. Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 2013;36:3411–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Strain WD, Cox X, Hirst M, Vencio S, Mohan V, Vokó Z, et al. Time to do more: addressing clinical inertia in the management of type 2 diabetes mellitus. Diabetes Res Clin Pract. 2014;105:302–12.

    Article  CAS  PubMed  Google Scholar 

  6. Retnakaran R, Yakubovich N, Qi Y, Opsteen C, Zinman B. The response to short-term intensive insulin therapy in type 2 diabetes. Diabetes Obes Metab. 2010;12:65–71.

    Article  CAS  PubMed  Google Scholar 

  7. Kramer CK, Choi H, Zinman B, Retnakaran R. Glycemic variability in patients with early type 2 diabetes: the impact of improvement in β-cell function. Diabetes Care. 2014;37:​1116–23.

    Article  CAS  PubMed  Google Scholar 

  8. Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on beta-cell function and glycemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet. 2008;371:1753–60.

    Article  CAS  PubMed  Google Scholar 

  9. Kramer CK, Zinman B, Retnakaran R. Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2013;1:28–34.

    Article  CAS  PubMed  Google Scholar 

  10. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.

    Article  Google Scholar 

  11. Holman RR, Paul SK, Bethel MA, Matthres DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.

    Article  CAS  PubMed  Google Scholar 

  12. ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319–28.

    Article  Google Scholar 

  13. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care. 2003;26:881–5.

    Article  PubMed  Google Scholar 

  14. Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP, Valk GD. Insulin monotherapy versus combinations of insulin with oral hypoglycemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(4):CD003418.

    Google Scholar 

  15. Standards of Medical Care in Diabetes – 2014. Diabetes Care. 2014;37(Suppl 1):S14–80.

    Google Scholar 

  16. Yki-Jarvinen H, Juurinen L, Alvarsson M, Bystedt T, Caldwell I, Davies M, et al. Initiate Insulin by Aggressive Titration and Education (INITIATE): a randomized study to compare initiation of insulin combination therapy in type 2 diabetic patients individually and in groups. Diabetes Care. 2007;30:1364–9.

    Article  CAS  PubMed  Google Scholar 

  17. Riddle MC, Rosenstock J, Gerich J, Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26:3080–6.

    Article  CAS  PubMed  Google Scholar 

  18. Holman RR, Farmer AJ, Davies MJ, Levy JC, Darbyshire JL, Keenan JF, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361:1736–47.

    Article  CAS  PubMed  Google Scholar 

  19. Hemmingsen B, Christensen LL, Wetterslev J, Vaag A, Gluud C, Lund SS, et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. BMJ. 2012;344, e1771.

    Article  PubMed  Google Scholar 

  20. Davies M, Storms F, Shutler S, Bianchi-Biscay M, Gomis R, ATLANTUS Study Group. Improvement of glycemic control in subjects with poorly controlled type 2 diabetes: comparison of two treatment algorithms using insulin glargine. Diabetes Care. 2005;28:1282–8.

    Article  CAS  PubMed  Google Scholar 

  21. Kooy A, de Jager J, Lehert P, Bets D, Wulffelé MG, Donker ABJ, et al. Metformin prevents weight gain and improves cardiovascular outcome in patients with type 2 diabetes intensively treated with insulin. Diabetes. 2007; 56(S1): Abstract 0578-P.

    Google Scholar 

  22. Grey A, Bolland M, Gamble G, Wattie D, Horne A, Davidson J. The peroxisome-proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab. 2007;92:1305–10.

    Article  CAS  PubMed  Google Scholar 

  23. Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care. 2002;12:2133–40.

    Article  Google Scholar 

  24. Hirst JA, Farmer AJ, Dyar A, Lung TW, Stevens RJ. Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Diabetologia. 2013;56:973–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Clar C, Royle P, Waugh N. Adding pioglitazone to insulin containing regimens in type 2 diabetes: systematic review and meta-analysis. PLoS One. 2009;4, e6112.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Fineman MS, Cirincione BB, Maggs D, Diamant M. GLP-1 based therapies: differential effects on fasting and postprandial glucose. Diabetes Obes Metab. 2012;14:675–88.

    Article  CAS  PubMed  Google Scholar 

  27. Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014;384:2228–34.

    Article  CAS  PubMed  Google Scholar 

  28. Raccah D, Lin J, Wang E, Germé M, Perfetti R, Bonadonna RC, et al. Once-daily prandial lixisenatide versus once-daily rapid-acting insulin in patients with type 2 diabetes mellitus insufficiently controlled with basal insulin: analysis of data from five randomized, controlled trials. J Diabetes Complications. 2014;28:40–4.

    Article  PubMed  Google Scholar 

  29. Robinson LE, Holt TA, Rees K, Randeva HS, O'Hare JP. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open. 2013;3, e001986.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gough S, Bode B, Woo V, Rodbard HW, Linjawi S, Poulsen P, et al. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014;2:885–9.

    Article  CAS  PubMed  Google Scholar 

  31. Buse JB, Vilsbøll T, Thurman J, Blevins TC, Langbakke IH, Bøttcher SG, et al. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014;37:2926–33.

    Article  CAS  PubMed  Google Scholar 

  32. Rosenstock J, Diamant M, Silvestre L, Souhami E, Zhou T, Fonseca V. Benefits of a fixed-ratio formulation of once-daily insulin glargine/lixisenatide (LixiLan) vs. glargine in type 2 diabetes inadequately controlled on metformin. Presented at the European Association for the Study of Diabetes (EASD) Annual Meeting, Vienna, 15–19th September 2014. Abstract 241.

    Google Scholar 

  33. Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther. 2014;5:1–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012;38:89–101.

    Article  CAS  PubMed  Google Scholar 

  35. Frandsen CS, Madsbad S. Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin treatment in patients with Type 2 diabetes: a review. Diabet Med. 2014;31:1293–300.

    Article  CAS  PubMed  Google Scholar 

  36. Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S, Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2014;16:124–36.

    Article  CAS  PubMed  Google Scholar 

  37. Matthews DR, Fulcher G, Perkovic V, de Zeeuw D, Mahaffey KW, Rosenstock J, et al. Efficacy and safety of canagliflozin (CANA), an inhibitor of sodium glucose co-transporter 2 (SGLT2), added-on to insulin therapy with or without oral agents in type 2 diabetes. Diabetologie Stoffwechsel. 2013;​8-P251.

    Google Scholar 

  38. Rosenstock J, Jelaska A, Wang F, Kim G, Broedl U, Woerle H-J. Empagliflozin as add-on to basal insulin for 78 weeks improves glycemic control with weight loss in insulin-treated type 2 diabetes (T2DM). Can J Diabetes. 2013;37:S32.

    Article  Google Scholar 

  39. Rosenstock J, Jelaska A, Frappin G, Salsali A, Kim G, Woerle HJ, et al; EMPA-REG MDI Trial Investigators. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37:1815–23.

    Google Scholar 

  40. Bergenstal RM, Johnson M, Powers MA, Wynne A, Vlajnic A, Hollander P, et al. Adjust to target in type 2 diabetes: comparison of a simple algorithm with carbohydrate counting for adjustment of mealtime insulin glulisine. Diabetes Care. 2008;31:1305–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Owens DR, Luzio SD, Sert-Langeron C, Riddle MC. Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month ‘proof-of-concept’ study. Diabetes Obes Metab. 2011;13:1020–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lankisch MR, Ferlinz KC, Leahy JL, Scherbaum WA; Orals Plus Apidra and LANTUS (OPAL) study group. Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two single-dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs. Diabetes Obes Metab. 2008;10:1178–85.

    Google Scholar 

  43. Riddle MC, Vlajnic A, Jones B, J, Rosenstock J. Comparison of 3 intensified insulin regimens added to oral therapy for type 2 diabetes: twice-daily aspart premixed vs glargine plus 1 prandial glulisine or stepwise addition of glulisine to glargine. Diabetes. 2011;60: Abstract 0409–PP.

    Google Scholar 

  44. Edelman SV, Liu R, Johnson J, Glass LC. AUTONOMY: the first randomized trial comparing two patient-driven approaches to initiate and titrate prandial insulin lispro in type 2 diabetes. Diabetes Care. 2014;37:2132–40.

    Article  CAS  PubMed  Google Scholar 

  45. Yki-Jarvïnen H, Kotronen A. Is there evidence to support use of premixed or prandial insulin regimens in insulin-naive or previously insulin-treated type 2 diabetic patients? Diabetes Care. 2013;36:S205–11.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Lasserson DS, Glasziou P, Perera R, Holman RR, Farmer AJ. Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses. Diabetologia. 2009;52:​1990–2000.

    Article  CAS  PubMed  Google Scholar 

  47. Giugliano D, Maiorino MI, Bellastella G, Chiodini P, Ceriello A, Esposito K. Efficacy of insulin analogs in achieving the hemoglobin A1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Care. 2011;34:510–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. American Diabetes Association (ADA). 6. Glycemic targets. Assessment of glycemic control. Diabetes Care. 2015;38 (Suppl 1): S3–40.

    Google Scholar 

  49. Wang C, Mamza J, Idris I. Biphasic vs basal bolus insulin regimen in Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabet Med. 2015;32:585–94.

    Google Scholar 

Further Reading

  • Crasto W, Jarvis J, Khunti K, Davies MJ. New insulins and new insulin regimens: a review of their role in improving glycaemic control in patients with diabetes. Postgrad Med J. 2009;85:257–67.

    Article  CAS  PubMed  Google Scholar 

  • Davies MJ, Gargliardino JJ, Gray LJ, Khunti K, Mohan V, Hughes R. Real-world factors affecting adherence to insulin therapy in patients with type 1 or type 2 diabetes mellitus: a systematic review. Diabet Med. 2013;30:512–24.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. George Eliot Hospital NHS Trust, Nuneaton, United Kingdom

    Winston Crasto

  2. Leicester Diabetes Centre, Leicester General Hospital, Leicester, United Kingdom

    Janet Jarvis & Melanie J. Davies

Authors
  1. Winston Crasto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janet Jarvis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melanie J. Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Crasto, W., Jarvis, J., Davies, M.J. (2016). Insulin Management in Type 2 Diabetes. In: Handbook of Insulin Therapies. Adis, Cham. https://doi.org/10.1007/978-3-319-10939-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-10939-8_4

  • Published:

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-10938-1

  • Online ISBN: 978-3-319-10939-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation