Skip to main content
SpringerLink
Log in

The treat-to-target A1C approach to control type 2 diabetes and prevent complications

  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Before initiating insulin therapy, clinicians often wait until oral antidiabetic agents fail to adequately reduce glycosylated hemoglobin (A1C) levels and control hyperglycemia in patients with type 2 diabetes. Long-term, randomized clinical trials demonstrate that reducing A1C to close to normal decreases rates of microvascular complications and can also reduce macrovascular complications. Insulin regimens that treat to target A1C levels may achieve greater control of hyperglycemia. Various randomized trials have assessed the efficacy and safety of initiating insulin therapy with human insulins and insulin analogs in patients with type 2 diabetes whose condition is inadequately controlled with oral antidiabetics. These studies assessed different regimens, including basal and premixed insulins, for their ability to reach target A1C goals and provided evidence-based protocols for the initiation and systematic dosage titration of insulin therapy in patients with type 2 diabetes. Examples of how to initiate and intensify insulin therapy to achieve target A1C goals based on these protocols are presented.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among US adults diagnosed with type 2 diabetes: a preliminary report.Diabetes Care. 2004; 27: 17–20.

    Article  PubMed  Google Scholar 

  2. Quest Diagnostics. Patients improved diabetes control over 5-year period, but many fail to achieve treatment goal: Quest Diagnostics Health Trends™ Diabetes Report is based on 14.3 million test results from 2001–2005 from the nation’s largest database of clinical lab results. Available at: http: //www.questdiagnostics.com/brand/business/healthtrends/diabetes/ diabetesreport.html. Accessed August 3, 2006.

  3. Nathan DM. Initial management of glycemia in type 2 diabetes mellitus.N Engl J Med. 2002; 347: 1342–1349.

    Article  PubMed  Google Scholar 

  4. Diabetes Control and Complications Trial Research Group. 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. 1993; 329: 977–986.

    Article  Google Scholar 

  5. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes.N Engl J Med. 2005; 353: 2643–2653.

    Article  PubMed  Google Scholar 

  6. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non—insulin-dependent diabetes mellitus: a randomized prospective 6-year study.Diabetes Res Clin Pract. 1995; 28: 103–117.

    Article  PubMed  CAS  Google Scholar 

  7. United Kingdom 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: 837–853.

    Article  Google Scholar 

  8. American Diabetes Association. Standards of medical care in diabetes—2006.Diabetes Care. 2006; 29(suppl 1): S4-S42.

    Google Scholar 

  9. American Association of Clinical Endocrinologists. The American Association of Clinical Endocrinologists medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management—2002 update.Endocr Pract. 2002; 8(suppl 1): 40–82.

    Google Scholar 

  10. International Diabetes Federation (IDF) Clinical Guidelines Task Force.Global Guideline for Type 2 Diabetes. Brussels: IDF; 2005.

    Google Scholar 

  11. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy.N Engl J Med. 2000; 342: 381–389.

    Article  Google Scholar 

  12. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort.Diabetes Care. 1999; 22: 99–111.

    Article  Google Scholar 

  13. Stratton IM, Alder AI, Neil HAW, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.BMJ. 2000; 321: 405–412.

    Article  PubMed  CAS  Google Scholar 

  14. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49).JAMA. 1999; 281: 2005–2012.

    Article  PubMed  CAS  Google Scholar 

  15. Wright A, Burden AC, Paisey RB, Cull CA, Holman RR. Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the UK Prospective Diabetes Study (UKPDS 57).Diabetes Care. 2002; 25: 330–336.

    Article  PubMed  CAS  Google Scholar 

  16. Riddle MC, Rosenstock J, Gerich J. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Hermansen K, Davies M, Derezinski T, et al. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes.Diabetes Care. 2006; 29: 1269–1274.

    Article  PubMed  CAS  Google Scholar 

  18. Janka HU, Plewe G, Riddle MC, et al. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes.Diabetes Care. 2005; 28: 254–259.

    Article  PubMed  CAS  Google Scholar 

  19. Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH. Combined therapy with insulin lispro mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy.Clin Ther. 2004; 26: 2034–2044.

    Article  PubMed  CAS  Google Scholar 

  20. Malone JK, Bai S, Campaigne BN, Reviriego J, Augendre-Ferrante B. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with type 2 diabetes.Diabet Med. 2005; 22: 374–381.

    Article  PubMed  CAS  Google Scholar 

  21. Raskin P, Allen E, Hollander P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs.Diabetes Care. 2005; 28: 260–265.

    Article  PubMed  CAS  Google Scholar 

  22. Garber AJ, Wahlen J, Wahl T, et al. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (the 1–2–3 study).Diabetes Obes Metab. 2006; 8: 58–66.

    Article  PubMed  CAS  Google Scholar 

  23. Davidson JA, Blonde L, Jellinger PS, Lebovitz HE, Parkin CG. Road map for the prevention and treatment of type 2 diabetes. Available at: http://www.aace.com/meetings/consensus/ odimplementation/roadmap.pdf. Accessed August 1, 2006.

  24. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycaemia in type 2 diabetes: 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. 2006; 49: 1711–1721.

    Article  PubMed  CAS  Google Scholar 

  25. Garber AJ. Premixed insulin analogues for the treatment of diabetes mellitus.Drugs. 2006; 66: 31–49.

    Article  PubMed  CAS  Google Scholar 

  26. Haak T, Tiengo A, Draeger E, Suntum M, Waldhausl W. Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes.Diabetes Obes Metab. 2005; 7: 56–64.

    Article  PubMed  CAS  Google Scholar 

  27. Chehade JM, Mooradian AD. Drug therapy: current and emerging agents. In: Sinclair AJ, Finucane P, eds.Diabetes in Old Age. 2nd ed. Chichester: John Wiley & Sons; 2001: 199–214.

    Google Scholar 

  28. Gin H, Hanaire-Broutin H. Reproducibility and variability in the action of injected insulin.Diabetes Metab. 2005; 31: 7–13.

    Article  PubMed  CAS  Google Scholar 

  29. Rosenstock J, Dailey G, Massi-Benedetti M, et al. Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes.Diabetes Care. 2005; 28: 950–955.

    Article  PubMed  CAS  Google Scholar 

  30. Oiknine R, Bernbaum M, Mooradian AD. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus.Drugs. 2005; 65: 325–340.

    Article  PubMed  CAS  Google Scholar 

  31. Mooradian AD, Bernbaum M, Albert SG. Narrative review: a rational approach to starting insulin therapy.Ann Intern Med. 2006; 145: 125–134.

    PubMed  CAS  Google Scholar 

  32. Hirsch IB. Insulin analogues.N Engl J Med. 2005; 352: 174–183.

    Article  PubMed  CAS  Google Scholar 

  33. Roach P, Woodworth JR. Clinical pharmacokinetics and pharmacodynamics of insulin lispro mixtures.Clin Pharmacokinet. 2002; 41: 1043–1057.

    Article  PubMed  CAS  Google Scholar 

  34. Brunelle RL, Llewelyn J, Anderson JH Jr, Gale EA, Koivisto VA. Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes.Diabetes Care. 1998; 21: 1726–1731.

    Article  PubMed  CAS  Google Scholar 

  35. Jacobsen LV, Sogaard B, Riis A. Pharmacokinetics and pharmacodynamics of a premixed formulation of soluble and protamine-retarded insulin aspart.Eur J Clin Pharmacol. 2000; 56: 399–403.

    Article  PubMed  CAS  Google Scholar 

  36. Weyer C, Heise T, Heinemann L. Insulin aspart in a 30/70 premixed formulation: pharmacodynamic properties of a rapid-acting insulin analog in stable mixture.Diabetes Care. 1997; 20: 1612–1614.

    Article  PubMed  CAS  Google Scholar 

  37. Luzio S, Dunseath G, Peter R, Pauvaday V, Owens DR. Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes.Diabetologia. 2006; 49: 1168.

    Article  CAS  Google Scholar 

  38. Kilo C, Mezitis N, Jain R, et al. Starting patients with type 2 diabetes on insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin.J Diabetes Complications. 2003; 17: 307–313.

    Article  PubMed  Google Scholar 

  39. Roach P, Yue L, Arora V. Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation. Humalog Mix25 Study Group.Diabetes Care. 1999; 22: 1258–1261.

    Article  PubMed  CAS  Google Scholar 

  40. Plank J, Bodenlenz M, Sinner F, et al. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir.Diabetes Care. 2005; 28: 1107–1112.

    Article  PubMed  CAS  Google Scholar 

  41. Yki-Jarvinen H, Kauppinen-Makelin R, Tiikkainen M, et al. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.Diabetologia. 2006; 49: 442–451.

    Article  PubMed  CAS  Google Scholar 

  42. Sun P, Wang R, Jacober SJ. Therapeutic effectiveness of two insulin regimens for insulin naive patients with type 2 diabetes mellitus: once-daily basal insulin or twice-daily premixed insulin.Diabetes. 2006;55(suppl 1). Abstract 101.

  43. Riddle MC. Making the transition from oral to insulin therapy.Am J Med. 2005; 118(suppl 5A): 14S-20S.

    Article  PubMed  CAS  Google Scholar 

  44. Meece J. Dispelling myths and removing barriers about insulin in type 2 diabetes.Diabetes Educ. 2006; 32: 9S-18S.

    Article  PubMed  Google Scholar 

  45. Yki-Jarvinen H. Insulin therapy in type 2 diabetes: role of the long-acting insulin glargine analogue.Eur J Clin Invest. 2004; 34: 410–416.

    Article  PubMed  CAS  Google Scholar 

  46. Shank ML, Del Prato S, DeFronzo RA. Bedtime insulin/daytime glipizide: effective therapy for sulfonylurea failures in NIDDM.Diabetes. 1995; 44: 165–172.

    Article  PubMed  CAS  Google Scholar 

  47. 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 HbA(1c).Diabetes Care. 2003; 26: 881–885.

    Article  PubMed  Google Scholar 

  48. Mayfield JA, White RD. Insulin therapy for type 2 diabetes: rescue, augmentation, and replacement of beta-cell function.Am Fam Physician. 2004; 70: 489–500.

    PubMed  Google Scholar 

  49. Bohannon NJ. Insulin delivery using pen devices: simple-to-use tools may help young and old alike.Postgrad Med. 1999; 106: 57–64,68.

    Article  PubMed  CAS  Google Scholar 

  50. Bohannon NJ, Ohannesian JP, Burdan AL, Holcombe JH, Zagar A. Patient and physician satisfaction with the Humulin®/Humalog® Pen, a new 3.0-mL prefilled pen device for insulin delivery.Clin Ther. 2000; 22: 1049–1067.

    Article  PubMed  CAS  Google Scholar 

  51. Raslova K, Bogoev M, Raz I, et al. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes [published correction appears inDiabetes Res Clin Pract. 2006;72: 112].Diabetes Res Clin Pract. 2004; 66: 193–201.

    Article  PubMed  CAS  Google Scholar 

  52. Liebl A, Prager R, Kaiser M, Binz K, Gallwitz B. Biphasic insulin aspart 30 (BIAsp30), insulin detemir (IDet) and insulin aspart (IAsp) allow patients with type 2 diabetes to reach A1C target: the PREFER study.Diabetes. 2006;55(suppl 1). Abstract 123.

  53. Strowig SM, Avilés-Santa ML, Raskin P. Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and troglitazone in type 2 diabetes.Diabetes Care. 2002; 25: 1691–1698.

    Article  PubMed  CAS  Google Scholar 

  54. Yki-Jarvinen H, Ryysy L, Nikkila K, et al. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus: a randomized, controlled trial.Ann Intern Med. 1999; 130: 389–396.

    PubMed  CAS  Google Scholar 

  55. Aviles-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.Ann Intern Med. 1999; 131: 182–188.

    PubMed  CAS  Google Scholar 

  56. Rosenstock J, Davies M, Home PD, et al. Insulin detemir added to oral anti-diabetic drugs in type 2 diabetes provides glycemic control comparable to insulin glargine with less weight gain.Diabetes. 2006;55(suppl 1). Abstract 132.

Download references

Author information

Authors and Affiliations

  1. Department of Community & Family Medicine, University of Missouri-Kansas City School of Medicine Truman Medical Center Lakewood, 7900 Lee’s Summit Road, 64139, Kansas City, MO

    Russell D. White MD

Authors
  1. Russell D. White MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Russell D. White MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

White, R.D. The treat-to-target A1C approach to control type 2 diabetes and prevent complications. Adv Therapy 24, 545–559 (2007). https://doi.org/10.1007/BF02848777

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02848777

Keywords

Search

Navigation