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. 2011 May;57(5):562.

Strategies for initiating insulin in type 2 diabetes

Christina Korownyk 1, Noah Ivers 2, G Michael Allan 3
PMCID: PMC3093589  PMID: 21571718

Clinical question

What is the optimal regimen for initiating insulin in type 2 diabetes (T2D)?

Evidence

Four reasonably sized randomized controlled trials address initiating insulin in T2D with poor glucose control.

  • The 4-T study1 followed 708 patients for 3 years, comparing long-acting basal insulin once daily, biphasic mixed insulin twice daily, and prandial insulin with meals.1
    • -Levels of glycated hemoglobin A1c (HbA1c) were not significantly different among the 3 groups.
      • —Significantly more patients in the basal and prandial groups attained HbA1c levels ≤ 7.0% (63% and 67%, respectively, vs 49% biphasic; P < .001).
    • -Those taking basal insulin had significantly (P < .05) ...
      • —less weight gain (3.6 kg) than patients using prandial (6.4 kg) or biphasic insulin (5.7 kg),
      • —fewer confirmed symptomatic hypoglycemic events per year (1.7 basal vs 3.0 biphasic vs 5.7 prandial), and
      • —higher total doses of insulin than biphasic patients.
    • -More patients using basal insulin (82%) also required a second type of insulin (vs 74% prandial, 68% biphasic).
  • The 3 other studies2–4 followed 160 to 418 patients (total 811) for 6 months to 1 year and compared basal with prandial,2 basal with biphasic,3 and biphasic with prandial4 insulin.
    • -Levels of HbA1c were generally similar, except biphasic insulin improved HbA1c 0.5% more than basal insulin in 1 study and got more people to HbA1c levels ≤ 7.0%.3
    • -Basal insulin had significantly less hypoglycemia than prandial (P < .001)2 or biphasic (P < .05)3 insulin and less weight gain than biphasic (P < .01)3 insulin.

Context

  • The 4-T study1 is given priority because it is the largest and longest and compares the 3 options. Fortunately, the remaining studies2–4 generally support those findings.

  • INSIGHT5 found initiating basal insulin in poorly controlled T2D resulted in significantly lower HbA1c levels than continued oral hypoglycemic agents did (P = .005).
    • -Mean HbA1c levels and rates of hypoglycemia were not different between patients of FPs and diabetes experts.6

  • Specialists are 5 times more likely to initiate insulin.7

Bottom line

In T2D poorly controlled with oral agents, initiating basal insulin results in similar HbA1c reductions compared with prandial or biphasic insulin and might cause less weight gain and hypoglycemia. Family physicians who start insulin are as effective as specialists.

Implementation

While newer insulin products have theoretical advantages, a meta-analysis found that compared with neutral protamine Hagedorn (NPH), longer-acting insulin offers little or no benefit but costs much more.8 Advantages from reductions in hypoglycemia are at high risk of bias.9 To initiate basal insulin, prescribe NPH, 10 units daily at bedtime, increasing by 1 unit each night until fasting blood glucose is 4 to 7 mmol/L, remembering to educate the patient about hypoglycemia.10 A printable document available online simplifies the process of prescribing insulin11: www.ocfp.on.ca/local/files/InsulinPrescription_Rev1.pdf.

Tools for Practice articles in Canadian Family Physician are adapted from articles published twice monthly on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

References

  • 1.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(18):1736–47. doi: 10.1056/NEJMoa0905479. [DOI] [PubMed] [Google Scholar]
  • 2.Bretzel RG, Nuber U, Landgraf W, Owens DR, Bradley C, Linn T. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008;371(9618):1073–84. doi: 10.1016/S0140-6736(08)60485-7. [DOI] [PubMed] [Google Scholar]
  • 3.Raskin P, Allen E, Hollander P, Lewin A, Gabbay RA, Hu P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care. 2005;28(2):260–5. doi: 10.2337/diacare.28.2.260. [DOI] [PubMed] [Google Scholar]
  • 4.Hirao K, Arai K, Yamauchi M, Takagi H, Kobayashi M. Six-month multicentric, open-label, randomized trial of twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11) Diabetes Res Clin Pract. 2008;79(1):171–6. doi: 10.1016/j.diabres.2007.08.011. [DOI] [PubMed] [Google Scholar]
  • 5.Gerstein HC, Yale JF, Harris SB, Issa M, Stewart JA, Dempsey E. A randomized trial of adding insulin glargine vs. avoidance of insulin in people with type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT study. Diabet Med. 2006;23(7):736–42. doi: 10.1111/j.1464-5491.2006.01881.x. [DOI] [PubMed] [Google Scholar]
  • 6.Harris S, Yale JF, Dempsey E, Gerstein H. Can family physicians help patients initiate basal insulin therapy successfully? Randomized trial of patient-titrated insulin glargine compared with standard oral therapy: lessons for family practice from the Canadian INSIGHT trial. Can Fam Physician. 2008;54:550–8. [PMC free article] [PubMed] [Google Scholar]
  • 7.Shah BR, Hux JE, Laupacis A, Zinman B, van Walraven C. Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians? Diabetes Care. 2005;28(3):600–6. doi: 10.2337/diacare.28.3.600. [DOI] [PubMed] [Google Scholar]
  • 8.Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ. 2009;180(4):385–97. doi: 10.1503/cmaj.081041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Allan GM, Virani AS. Edmonton, AB: Alberta College of Family Physicians; 2010. Tools for Practice: the long and short of long acting insulin analogues (versus NPH)? Available from: www.acfp.ca/docs10/Insulin%20Analogues%20_versus%20NPH_pdf. Accessed 2011 Feb 25. [Google Scholar]
  • 10.British Columbia Guidelines and Protocols Advisory Committee . Diabetes care. Vancouver, BC: British Columbia Ministry of Health; 2010. Available from: www.bcguidelines.ca/gpac/pdf/diabetes.pdf. Accessed 2011 Feb 25. [Google Scholar]
  • 11.Ontario College of Family Physicians . Insulin prescription. Toronto, ON: Ontario College of Family Physicians; 2010. Available from: www.ocfp.on.ca/local/files/InsulinPrescription_Rev1.pdf. Accessed 2011 Feb 25. [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

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