Pharmacotherapy in Type 1 Diabetes

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee

Angela McGibbon MD, PhD, FRCPC Cindy Richardson MD, FRCPC Cheri Hernandez RN, PhD, CDE John Dornan MD, FRCPC, FACP

  • Key Messages
  • Recommendations
  • Figures
  • Highlights
  • Full Text
  • References

Key Messages

  • Basal-bolus insulin regimens (e.g. multiple daily injections or continuous subcutaneous insulin infusion) are the insulin regimens of choice for all adults with type 1 diabetes.
  • Insulin regimens should be tailored to the individual’s treatment goals, lifestyle, diet, age, general health, motivation, hypoglycemia awareness status and ability for self-management.
  • All individuals with type 1 diabetes should be counseled about the risk, prevention and treatment of insulin-induced hypoglycemia.

Highlights of Revisions

  • Echoes and expands upon the 2008 key messages of the importance of individualizing insulin regimens and educating patients about insulin-induced hypoglycemia.
  • A new appendix of cost for pharmacological agents (for type 1 and type 2 diabetes) has been added.
Table 1
Types of insulin
Physicians should refer to the most current edition of Compendium of Pharmaceuticals and Specialties (Canadian Pharmacists Association, Ottawa, Ontario, Canada) and product monographs for detailed information.
Insulin type (trade name) Onset Peak Duration
Bolus (prandial) insulins
Rapid-acting insulin analogues (clear)      
Insulin aspart (NovoRapid®) 10–15 min 1–1.5 h 3–5 h
Insulin glulisine (Apidra®) 10–15 min 1–1.5 h 3–5 h
Insulin lispro (Humalog®) 10–15 min 1–2 h 3.5–4.75 h
Short-acting insulins (clear)      
Humulin®-R 30 min 2–3 h 6.5 h
Novolin®ge Toronto
 
Basal insulins
Intermediate-acting (cloudy)      
Humulin®-N 1–3 h 5–8 h Up to 18 h
Novolin® ge NPH
Long-acting insulin analogues (clear)      
Insulin detemir (Levemir®) 90 min Not applicable Up to 24 h (glargine 24 h, detemir 16–24 h)
Insulin glargine (Lantus ®)
Premixed insulins
Premixed regular insulin–NPH (cloudy)
Humulin ® 30/70
Novolin ® ge 30/70, 40/60, 50/50
A single vial or cartridge contains a fixed ratio of insulin (% of rapid-acting or short-acting insulin to % of intermediate-acting insulin)
Premixed insulin analogues (cloudy)
Biphasic insulin aspart (NovoMix ® 30)
Insulin lispro/lispro protamine (Humalog ® Mix25 and Mix50)
     

Recommendations

Insulin regimens for type 1 diabetes

  1. 1.To achieve glycemic targets in adults with type 1 diabetes, basal-bolus insulin regimens or CSII as part of an intensive diabetes management regimen should be used [Grade A, Level 1A (1)].
  2. 2.Rapid-acting bolus insulin analogues, in combination with adequate basal insulin, should be used instead of regular insulin to minimize the occurrence of hypoglycemia, improve A1C [Grade B, Level 2 (2-4)] and achieve postprandial glucose targets [Grade B, Level 2 (4,5)].
  3. 3.Rapid-acting insulin analogues (aspart or lispro) should be used with CSII in adults with type 1 diabetes [Grade B, Level 2 (6,7)].
  4. 4.A long-acting insulin analogue (detemir, glargine) may be used as the basal insulin [Grade B, Level 2 (8-11)] to reduce the risk of hypoglycemia [Grade B, Level 2 (12) for detemir; Grade C, Level 3 (13) for glargine], including nocturnal hypoglycemia [Grade B, Level 2 (12) for detemir; Grade D, Consensus for glargine].

Hypoglycemia

  1. 5.All individuals with type 1 diabetes should be counselled about the risk and prevention of insulin-induced hypoglycemia, and risk factors for severe hypoglycemia should be identified and addressed [Grade D, Consensus].
  2. 6.In individuals with hypoglycemia unawareness, the following strategies may be used to reduce the risk of hypoglycemia and to attempt to regain hypoglycemia awareness:
    1. a.Increased frequency of SMBG, including periodic assessment during sleeping hours [Grade D, Consensus]
    2. b.Less stringent glycemic targets with avoidance of hypoglycemia for up to 3 months [Grade C, Level 3 (14,15)]
    3. c.A psychobehavioural intervention program (blood glucose awareness training) [Grade B, Level 2 (16)]

Abbreviations:
CSII, continuous subcutaneous insulin infusion; SMBG, self-monitoring of blood glucose.

References

  1. DeVries JH, Snoek FJ, Kostense PJ, et al, Dutch Insulin Pump Study Group. A randomized trial of continuous subcutaneous insulin infusion and intensive injection therapy in type 1 diabetes for patients with long-standing poor glycemic control. Diabetes Care 2002;25:2074-80.
  2. Siebenhofer A, Plank J, Berghold A, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev 2006;2:CD003287.
  3. Plank J, Siebenhofer A, Berghold A, et al. Systematic review and meta-analysis of short-acting insulin analogues in patients with diabetes mellitus. Arch Intern Med 2005;165:1337-44.
  4. Gough S. A review of human and analogue insulin trials. Diabetes Res Clin Pract 2007;77:1-15.>
  5. DeVries JH, Lindholm A, Jacobsen JL, et al, Tri-Continental Insulin Aspart Study Group. A randomized trial of insulin aspart with intensified basal NPH insulin supplementation in people with type 1 diabetes. Diabet Med 2003;20:312-8.
  6. Zinman B, Tildesley H, Chiasson JL, et al. Insulin lispro in CSII: results of a double-blind crossover study. Diabetes 1997;46:440-3.
  7. Bode B, Weinstein R, Bell D, et al. Comparison of insulin aspart with buffered regular insulin and insulin lispro in continuous subcutaneous insulin infusion: a randomized study in type 1 diabetes. Diabetes Care 2002;25:439-44.
  8. Warren E, Weatherley-Jones E, Chilcott J, et al. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health Technol Assess 2004;8:1-57.
  9. Wang F, Carabino JM, Vergara CM. Insulin glargine: a systematic review of a long-acting insulin analogue. Clin Ther 2003;25:1541-77.
  10. Dunn CJ, Plosker GL, Keating GM, et al. Insulin glargine: an updated review of its use in the management of diabetes mellitus. Drugs 2003;63:1743-78.
  11. Chapman TM, Perry CM. Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus. Drugs 2004;64:2577-95.
  12. Goldman-Levine JD, Lee KW. Insulin detemir: a new basal insulin analog. Ann Pharmacother 2005;39:502-7.
  13. Mullins P, Sharplin P, Yki-Jarvinen H, et al. Negative binomial meta-regression analysis of combined glycosylated hemoglobin and hypoglycemia outcomes across eleven phase III and IV studies of insulin glargine compared with neutral protamine Hagedorn insulin in type 1 and type 2 diabetes mellitus. Clin Ther 2007;29:1607-19.
  14. Cryer PE. Banting Lecture. Hypoglycemia: the limiting factor in the management of IDDM. Diabetes 1994;43:1378-89.
  15. The DCCT Research Group. Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med 1991;90:450-9.
  16. Berlin I, Sachon CI, Grimaldi A. Identification of factors associated with impaired hypoglycaemia awareness in patients with type 1 and type 2 diabetes mellitus. Diabetes Metab 2005;31:246-51.

 

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