Applied Evidence

Using prandial insulin to achieve glycemic control in type 2 diabetes

J Fam Pract. 2007 September;56(9):735-741

References

1. Bonora E, Corrao G, Bagnardi V, et al. Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia 2006;49:846-854.

2. Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care 1999;22:920-924.

3. The DECODE study group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999;354:617-621.

4. Decode Study Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care 2003;26:688-696.

5. Bonora E, Muggeo M. Postprandial blood glucose as a risk factor for cardiovascular disease in type II diabetes: the epidemiological evidence. Diabetologia 2001;44:2107-2114.

6. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA1c: analysis of glucose profiles and HbA1c in the Diabetes Control and Complications Trial. Diabetes Care 2002;25:275-278.

7. 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;26:881-885.

8. Stratton IM, Adler AI, Neil HAW, et al. on behalf of the UK Prospective Diabetes Study Group. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-412.

9. ACE/AACE Diabetes Road Map Task Force. American Association of Clinical Endocrinologists Website. Road map for the prevention and treatment of type 2 diabetes. Available at: www.aace.com/meetings/consensus/odimplementation/roadmap.pdf. Accessed August 6, 2007.

10. Riddle MC, Rosenstock J. Oral monotherapy and combination therapy. In: Cefalu WT, Gerich JE, Le-Roith D, eds. The CADRE Handbook of Diabetes Management. New York, NY: Medical Information Press;2004:127-144.

11. Sheehan MT. Current therapeutic options in type 2 diabetes mellitus: a practical approach. Clin Med Res 2003;1:189-200.

12. Giorgino F, Laviola L, Leonardini A. Pathophysiology of type 2 diabetes: rationale for different oral antidiabetic treatment strategies. Diabetes Res Clin Pract 2005;68(suppl 1):S22-S29.

13. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29:1963-1972.

14. American Diabetes Association. Standards of medical care in diabetes—2007. Diabetes Care 2007;30(suppl 1):S4-S41.

15. Lam S, See S. Exenatide: a novel incretin mimetic agent for treating type 2 diabetes mellitus. Cardiol Rev 2006;14:205-211.

16. Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: A randomized trial. Ann Intern Med 2005;143:559-569.

17. Kennedy L. Exenatide versus glargine—complementary therapies rather than competing [electronic letter]. Ann Intern Med 2005; 143. Available at: www.annals.org/cgi/eletters/143/8/559#2404. Accessed August 3, 2007.

18. Feinglos MN, Saad MF, Pi-Sunyer FX, An B, Santiago O. on behalf of the Liraglutide Dose-Response Study Group. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes. Diabetes Med 2005;22:1016-1023.

19. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE. for the Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006;29:2632-2637.

20. Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006;49:2564-2571.

21. Miller SA, St Onge EL. Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother 2006;40:1336-1343.

22. Herman GA, Bergman A, Liu F, et al. Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol 2006;46:876-886.

23. Wright A, Burden ACF, Paisey RB, Cull CA, Holman RR. for the UK Prospective Diabetes Study Group. 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.

24. Riddle MC, Rosenstock J, Gerich J. on behalf of the 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;26:3080-3086.

25. Raslová K, Bogoev M, Raz I, Leth G, Gall MA, Hâncu N. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract 2004;66:193-201.

26. Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. on behalf of the Levemir Treat-to-Target Study. 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-naïve people with type 2 diabetes. Diabetes Care 2006;29:1269-1274.

27. Davies M, Storms F, Shutler S, Bianchi-Biscay M, Gomis R, Lantus Study Group. AT.LANTUS trial investigating treatment algorithms for insulin glargine (LANTUS): results of the Type 2 Study [abstract]. Diabetes 2004;53(suppl 2):A473.-Abstract 1980 PO.

28. Ryysy L, Yki-Jarvinen H, Hänninen J. Simplifying treat to target—the LANMET study. In: Program and abstracts of the 40th European Association for the Study of Diabetes Annual Meeting. 2004;No. 749. PS 064.

29. Leahy JL. Intensive insulin therapy in type 1 diabetes mellitus. In: Leahy, JL, Cefalu WT, eds. Insulin Therapy New York, NY: Marcel Dekker;2002:87-112.

30. Bergenstal R, Johnson ML, Powers MA, Wynne AG, Vlajnic A, Hollander PA. Using a simple algorithm (ALG) to adjust mealtime glulisine (GLU) based on pre-prandial glucose patterns is a safe and effective alternative to carbohydrate counting (Carb Count). Diabetes 2006;55(suppl 1):A105.-

31. Overmann H, Heinemann L. Injection-meal interval: recommendations of diabetologists and how patients handle it. Diabetes Res Clin Pract 1999;43:137-142.

32. Wittlin SD, Woehrle HJ, Gerich JE. Insulin pharmacokinetics. In: Leahy JL, Cefalu WT, eds. Insulin Therapy New York, NY: Marcel Dekker;2002:73-85.

33. Becker RHA, Frick AD, Burger F, Potgieter JH, Scholtz H. Insulin glulisine, a new rapid-acting insulin analogue, displays a rapid time-action profile in obese non-diabetic subjects. Exp Clin Endocrinol Diabetes 2005;13:435-443.

34. Chase HP, Lockspeiser T, Peery B, et al. The impact of the diabetes control and complications trial and humalog insulin on glycohemoglobin levels and severe hypoglycemia in type 1 diabetes. Diabetes Care 2001;24:430-434.

35. Dailey G, Rosenstock J, Moses RG, Ways K. Insulin glulisine provides improved glycemic control in patients with type 2 diabetes. Diabetes Care 2004;27:2363-2368.

36. Apidra [package insert] Kansas City, Mo: Aventis Pharmaceuticals Inc;2004.

37. Lankisch M, Stahr B, Alawi H, Ferlinz K, Scherbaum W. Basal insulin and oral antihyperglycemic therapy (BOT) plus a single dose of insulin glusine at breakfast or at the predominant meal lower HbA1c in patients with type 2 diabetes. Diabetes 2006;55(suppl 1).:Abstract 514-P.

38. Rosenstock J, Zinman B, Murphy LJ, et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in type 2 diabetes: a randomized, controlled trial. Ann Intern Med 2005;143:549-558.

39. DeFronzo RA, Bergenstal RM, Cefalu WT, et al. Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: a 12-week, randomized, comparative trial. Diabetes Care 2005;28:1922-1928.

40. Exubera [package insert] New York, NY: Pfizer Inc;2006.

41. Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174-183.

Once you have this 24-hour insulin dose, you’ll then need to calculate the dose of basal insulin, which is 50% of the 24-hour total insulin dose, administered once daily. The remaining 50% of the total 24-hour dose provides prandial insulin coverage and is usually administered as follows:

30% to 40% at breakfast
30% at lunch
30% to 40% at dinner

Patients will need to adjust prandial insulin doses based on self-monitored blood glucose values.

Premixed insulin formulations

You should have your patients administer basal-prandial insulin as separate injections (eg, insulin glargine and insulin glulisine,³⁰ or insulin detemir and insulin aspart²⁵). The premixed (NPH based) formulations provide fixed doses of an intermediate-or long-acting insulin combined with a short-acting insulin. Although this method may be convenient to administer, it is more rigid and may not account for mealtimes and exercise. As a result, insulin levels will not match physiological insulin and thus, the risk for hypoglycemia increases. Another disadvantage is that adjustments to the dose based on self-monitored glucose levels are not possible with pre-mixed formulations.⁴¹

FAST TRACK

Patients with newly diagnosed type 2 diabetes and A_1c levels over 10% will benefit from a basal-prandial regimen

Separating the basal and prandial insulin components allows the insulin regimen to be adapted to an individual’s needs, thereby providing glycemic control with less propensity for hypoglycemia.

Acknowledgments

This article was supported by Sanofi-Aventis US. While the author is responsible for all content, he gratefully acknowledges the embryon scientific staff, who assisted in the preparation of a first draft of this article based on an author-approved outline, and also assisted in implementing author revisions.

Correspondence
George E. Dailey, MD, Senior Consultant, Division of Diabetes and Endocrinology, Head, Diabetes Research, Scripps Clinic, 10666 N. Torrey Pines Road, La Jolla, CA 92037; dailey.george@scrippshealth.org