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Can Fam Physician
Vol. 55, No. 6, June 2009, pp.608 - 611
Copyright © 2009 by The College of Family Physicians of Canada
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RxFiles

Taking the stress out of insulin initiation in type 2 diabetes mellitus

Tessa Laubscher, MB ChB CCFP FCFP
Assistant Professor of Academic Family Medicine at the University of Saskatchewan in Saskatoon

Loren Regier
Program Coordinator of the RxFiles Academic Detailing Program for Saskatoon Health Region

Brent Jensen
Pharmacist for the RxFiles Academic Detailing Program

Correspondence: Mr Regier, Saskatoon Health Region, RxFiles Academic Detailing, c/o Saskatoon City Hospital, 701 Queen St, Saskatoon, SK S7K 0M7; telephone 306 655-8505; fax 306 655-7980; e-mail regierl{at}rxfiles.ca; website www.RxFiles.ca

For many family physicians, initiating insulin therapy in people with type 2 diabetes mellitus (DM) can be anxiety-provoking and time-consuming. Often it is physicians’ lack of confidence in starting insulin, not patients’ fear of insulin injections, that delays optimizing glycemic control. Accessing resources such as diabetes treatment guidelines,1–3 RxFiles Drug Comparison Charts, and the services of pharmacists or diabetes educators can help take the stress out of this important aspect of diabetes care. The current debate over the uncertain benefits and risks of tight glucose control is beyond the scope of this article, but is discussed in the RxFiles "Diabetes—Glucose Control: Landmark Outcome Trials—Summary," available on CFPlus.*

Case

Tom is a 72-year-old man who has type 2 DM, hypertension, hyperlipidemia, and stable angina. He has had type 2 DM for about 14 years; until recently, his blood glucose (BG) levels were well controlled with combinations of oral hypoglycemic agents (OHAs), diet, and regular exercise. Over the past year his glycosylated hemoglobin A1c (HbA1c) levels have climbed; last month they were measured at 9.2%. This translates to an estimated average glucose (eAG) level of 12.1 mmol/L.4 Recent self-monitored BG readings include the following: fasting 8.9 to 11.2 mmol/L; before lunch 7.8 to 9.2 mmol/L; 1 hour after lunch 10.9 to 13.4 mmol/L; before supper 9.9 to 10 mmol/L.
Current diabetes medications include 1000 mg of metformin twice daily, 30 mg of pioglitazone daily, and 60 mg of gliclazide daily. He is taking optimal therapy for cardiovascular protection, including blood pressure control and statin therapy, which have proven outcome benefits.
In the clinic, you review Tom’s recent HbA1c and BG values; he informs you that he is following the diet guidelines recommended by the dietitian 6 months ago and is exercising for 30 to 60 minutes most days. A recent 2-kg weight loss confirms Tom’s lifestyle management progress. Tom asks you, "What else can I do to improve my blood sugars?"
While it is tempting to avoid the "inconvenience" of initiating insulin therapy at this clinic visit, it might be the preferred option for pursuing glycemic control. Tom is already taking adequate doses of 3 classes of OHAs.5 Further dose increases are unlikely to result in substantial reduction in glucose levels and might increase his risk of side effects. Sitagliptin could be considered, given its postprandial effect and minimal weight gain; however, it lacks outcome evidence and long-term safety data and reduces HbA1c by only about 0.7%.6 There is no evidence supporting its role as an add-on therapy to 3 other classes of OHAs.

Type 2 diabetes is characterized by insulin resistance and progressive decline in pancreatic β-cell function and endogenous insulin production.1 Physicians and patients need to acknowledge the progressive nature of type 2 DM and make appropriate advances in diabetic therapy (diet and lifestyle -> OHAs -> insulin). Because he has had type 2 DM for 14 years, Tom’s pancreas might not be able to produce adequate amounts of insulin even with additional OHA therapy. Thus insulin is an appropriate step-up therapy.

Successful initiation of insulin might be facilitated by the following considerations7,8:

  • Explain the rationale for starting insulin, emphasizing the progressive nature of type 2 DM and not blaming the patient. A demonstration of how insulin injections can be easily administered with a pen device allays many fears and misconceptions that people have about insulin, needles, and syringes (Box 19).
  • To avoid large drops in BG levels and ensure patient adherence, start with a low dose of basal insulin (eg, intermediate-acting insulin) at 5 to 10 units or 0.1 to 0.2 units/kg total body weight at bedtime. Give the patient written instructions on titrating the dose (eg, increase by 2 units every 3 days until fasting glucose < 7 mmol/L).1 Avoid dosage increases if the patient experiences nocturnal hypoglycemia or 2 or more episodes of BG levels below 4 mmol/L.
  • Contact the patient’s pharmacist or diabetes educator and ask him or her to provide instruction on use of the insulin delivery device and dosage adjustment if you are not able to do this in your practice.
  • Metformin therapy should generally be continued when initiating insulin if it is not contraindicated (eg, in acute heart failure). Metformin has outcome evidence for reduced mortality, results in less weight gain from insulin, and might decrease the required insulin dose.10,11 Thus metformin can be continued even with multiple daily insulin injection regimens. Caution and dose reduction are required in patients with moderate renal impairment (creatinine clearance 30 to 60 mL/min).1,2
  • Sulfonylureas (eg, gliclazide) might contribute to glycemic control when once-daily basal insulin is used, but should usually be discontinued if mealtime short-acting or rapid insulin is added. Thiazolidinediones (eg, pioglitazone, rosiglitazone) are not approved for use with insulin and are usually discontinued owing to the increased risks of edema, heart failure, and weight gain.12,13
  • Hypoglycemia is rare in patients with type 2 DM taking combinations of metformin and basal intermediate- or long-acting insulin. However, all patients using insulin should learn the risks, symptoms, and treatment of hypoglycemia.1,7
  • Self-monitoring of BG needs to be individualized.1,7 Type 2 DM patients taking insulin will need to monitor BG more frequently. Preprandial and postprandial BG levels are required to decide if and when to start mealtime insulin therapy.
  • Individualize treatment goals balancing uncertain benefits with potential risks and difficulties of tighter glucose control.1,14


Box 1 Starting insulin in type 2 diabetes mellitus: Tips for patient buy-in


  • Discuss insulin early to change negative perceptions about insulin
  • Provide information about insulin benefits
  • Consider suggesting a "trial" for 1 month
  • Discuss the relative ease of using the newer insulin devices (eg, insulin pens, smaller needle) compared with syringes and vials (see also RxFiles Insulin Pen Delivery Devices chart at www.RxFiles.ca*)
  • Link patient to community support, such as a certified diabetes educator, for education on injections and monitoring
  • Ensure patient has time to get comfortable with loading and working a pen (or syringe)
  • Refer patient for nutrition and physical activity counseling

Adapted from Starting Insulin.9

 

Most patients with type 2 DM have few problems with insulin therapy when it is started once daily in addition to metformin. Once comfortable with basal insulin therapy, they are more willing to accept the introduction of bolus (short-acting or rapid) insulin (Table 18) before meals for better postprandial glycemic control.1,2


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  		Table 1 Insulin available in Canada

 
There is some debate about the role of long-acting insulin analogues (LAIAs) in the initiation of basal insulin therapy in patients with type 2 DM. While some authors suggest a prominent role, recent systematic reviews have found that LAIAs offer little advantage over neutral protamine Hagedorn (NPH) for initial therapy.15–18 The primary advantage of LAIAs is the potential for less nocturnal hypoglycemia in some patients; HbA1c and weight end points are similar to those seen with intermediate-acting insulin15,16 and outcome evidence is lacking. Newer LAIAs cost more than twice as much as intermediate-acting insulin (Table 18). Further advantages and disadvantages of the different types of insulin are outlined in Table 2.15–22


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  		Table 2 Advantages and disadvantages of insulin: Evidence for insulin analogues is limited to small, short-term trials, and benefits are modest; anecdotal experience is favourable. Recent systematic and economic reviews rigorously assessed benefits, risks, and incremental cost.15–22

 

RxFiles is an academic detailing program providing objective comparative drug information. RxFiles incorporates information from family physicians, other specialists, and pharmacists with an extensive review of the literature to produce newsletters, question-and-answer summaries, trial summaries, and drug comparison charts. The RxFiles Drug Comparison Charts book and website have become practical tools for evidence-based and clinically relevant drug use information throughout Canada. For more information, go to www.RxFiles.ca.

 

Footnotes

* The "Diabetes—Glucose Control: Landmark Outcome Trials—Summary," the insulin pen delivery devices chart, an approach to management of type 2 diabetes in adults chart, an insulin comparison chart, and "Insulin Management: Evidence, Tips & Pearls" are available at www.cfp.ca. Go to the full text of the article on-line, then click on CFPlus in the menu at the top right of the page. Back

Competing interests

RxFiles and contributing authors do not have any commercial competing interests. RxFiles Academic Detailing Program is funded through a grant from Saskatchewan Health to Saskatoon Health Region; additional "not for profit; not for loss" revenue is obtained from sale of books and on-line subscriptions.

References

  1. Canadian Diabetes Association. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32(Suppl_1):S1–201. Available from: www.diabetes.ca/files/cpg2008/cpg-2008.pdf. Accessed 2009 Apr 21.
  2. American Diabetes Association. Standards of medical care in diabetes—2008. . Diabetes Care 2009;32(Suppl 1):S12–54. Available from: http://care.diabetesjournals.org/content/vol31/Supplement_1/. Accessed 2009 Apr 21.
  3. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32(1):193–203. Available from: http://care.diabetesjournals.org/cgi/reprint/32/1/193. Accessed 2009 Apr 27.[Abstract/Free Full Text]
  4. Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ. Translating the A1c assay into estimated average glucose values. Diabetes Care 2008;31(8):1473–8. Available from: http://professional.diabetes.org/Glucosecalculator.aspx. Accessed 2009 Apr 27.[Abstract/Free Full Text]
  5. Regier L, Jensen B. Oral hypoglycemic agents comparison chart. RxFiles drug comparison charts. 7th ed ed. Saskatoon, SK: Saskatoon Health Region; 2008. p. 25Available from: wwwRxFilesca Accessed 2009 Apr 27.
  6. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008;(2):CD006739.
  7. Jin M, Regier L, Jensen B. RxFiles insulin management: evidence, tips & pearls. RxFiles drug comparison charts. 7th ed ed. Saskatoon, SK: Saskatoon Health Region; 2008. p. 26b–7. Available from: www.RxFiles.ca. Accessed 2009 Apr 17.
  8. Regier L, Jensen B, Downey S. Insulin comparison chart. RxFiles drug comparison charts. 7th ed ed. Saskatoon, SK: Saskatoon Health Region; 2008. p. 26b–7. Available from: www.RxFiles.ca. Accessed 2009 Apr 17.
  9. Knowledge Support Service, Centre for Effective Practice. Starting insulin. Toronto, ON: Department of Family and Community Medicine, University of Toronto; 2008.
  10. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352(9131):854–65.[Medline]
  11. Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1999;130(5):389–96.[Abstract/Free Full Text]
  12. e-CPS [database on the Internet]Ottawa, ON: Canadian Pharmacists Association; 2009.
  13. Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004;27(1):256–63.[Free Full Text]
  14. Montori V, Fernandez-Balsells M. Glycemic control in type 2 diabetes: time for an evidence-based about face? Ann Int Med 2009;150(11Epub ahead of print. Available from: www.annals.org/cgi/content/full/0000605200906020-00118v1. Accessed 2009 Apr 21.
  15. Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J, et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2007;(2):CD005613.
  16. Canadian Agency for Drugs and Technologies in Health. Optimal therapy recommendations for the prescribing and use of insulin analogues. Can Optimal Med Prescr Util Serv 2009;2(7):1–79. Available from: www.cadth.ca/media/pdf/compus_IA_OT_rec_report.pdf. Accessed 2009 Apr 14.
  17. Schooff MD, Gupta L. Are long-acting insulin analogues better than isophane insulin? Am Fam Physician 2008;77(4):447–9.[Medline]
  18. Canadian Agency for Drugs and Technologies in Health. An economic evaluation of insulin analogues for the treatment of patients with type 1 and type 2 diabetes mellitus in Canada. Can Optimal Med Prescr Util Serv 2008;2(4):1–52. Available from: www.cadth.ca/media/compus/reports/compus_Economic_IA_Report.pdf. Accessed 2009 Apr 17.
  19. Siebenhofer A, Plank J, Berghold A, Jeitler K, Horvath K, Narath M, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev 2006;(2):CD003287.
  20. Qayyum R, Bolen S, Maruthur N, Feldman L, Wilson LM, Marinopoulos SS, et al. Systematic review: comparative effectiveness and safety of premixed insulin analogues in type 2 diabetes. Ann Intern Med 2008;149(8):549–59.[Abstract/Free Full Text]
  21. Rolla A. Pharmacokinetic and pharmacodynamic advantages of insulin analogues and premixed insulin analogues over human insulins: impact on efficacy and safety. Am J Med 2008;121(6 Suppl):S9–19.[Medline]
  22. Singh S, 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.[Abstract/Free Full Text]




This Article
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Right arrow Articles by Laubscher, T.
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Right arrow Articles by Laubscher, T.
Right arrow Articles by Jensen, B.

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