Using prandial insulin to achieve glycemic control in type 2 diabetes

,

Applied Evidence

Using prandial insulin to achieve glycemic control in type 2 diabetes

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

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References

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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.

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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.

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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.-

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A guide to basal insulin dosing and titration

Initiate basal insulin with a 10 U once-daily dose of insulin glargine, insulin detemir, or NPH insulin.²⁴ (Note: NPH insulin and insulin detemir may require twice-daily dosing.)²⁵
Titrate weekly to a target fasting plasma glucose [FPG] of ≤100 mg/dL based on the average self-monitored FPG values from the preceding 2 days as follows:²⁴
- If FPG is ≥180 mg/dL, increase insulin dosage by 8 U/d.
- If FPG is 140–180 mg/dL, increase insulin dosage by 6 U/d.
- If FPG is 120–140 mg/dL, increase insulin dosage by 4 U/d.
- If FPG is 100–120 mg/dL, increase insulin dosage by 2 U/d.
- If FPG is <72 mg/dL at any time during the week, do not increase insulin dosage.
- If FPG is <56 mg/dL, decrease insulin dosage by 2–4 U/d.

Keep in mind…

A similar titration schedule to the one described here was effective in a study with insulin detemir and NPH insulin.²⁶
An alternative titration strategy to the one here would be to increase basal insulin dose by 2 U every 3 days to reach an FPG level of ≤100 mg/dL.^27,28
Less stringent A_1c goals may be appropriate for patients with limited life expectancies, very young children, the elderly, and individuals with comorbid conditions.¹⁴

Rapid-acting analogs allow more flexible administration

Prior to the development of rapid-acting insulin analogs, regular human insulin (RHI) was the only available insulin suitable for prandial glycemic control. However, it had significant limitations, including the need for it to be injected 30 to 45 minutes before eating (and the poor compliance with this requirement), variability in peak levels (between patients and with the same patient), variability in absorption based on injection site, and frequent episodes of hypoglycemia.^31,32

Newer rapid-acting insulin analogs such as insulin aspart, insulin glulisine, and insulin lispro demonstrate improved pharmacokinetic profiles with more rapid onset, faster time to peak activity, and shorter duration of action than RHI.^32,33 These rapid-acting analogs allow administration right before or right after a meal, resulting in improved glycemic control without increased hypoglycemia or weight gain.^34,35 Whereas the rapid onset of action of these analogs allows for administration 5 to 15 minutes before a meal, the patient can administer insulin glulisine within 20 minutes of the start of the meal.³⁶ The addition of just 1 dose of prandial insulin to existing basal insulin plus oral antidiabetic drug therapy offers patients a substantial benefit.³⁷

A new option: inhaled insulin

The US Food and Drug Administration recently approved an inhaled prandial insulin. Research has shown that it effectively addresses postprandial glucose excursions for patients with type 2 diabetes.^38,39 A 12-week trial comparing A_1c levels among patients switched to inhaled insulin (Exubera) before meals (n=76) or rosiglitazone (Avandia) 4 mg twice daily (n=69) found that inhaled insulin reduced A1c to a greater degree than rosiglitazone (–2.3% vs –1.4%); however, patients receiving inhaled insulin experienced a greater incidence of hypoglycemia (0.7 vs 0.05 episodes per subject-month).³⁹

FAST TRACK

Adding just 1 prandial dose to a regimen of basal insulin and oral anti-diabetic drugs offers substantial benefits

Inhaled insulin can be used as monotherapy or in conjunction with oral agents or a long-acting basal insulin. Inhaled insulin has a rapid onset of action (within 10–20 minutes, comparable with rapid-acting insulin analogs) and a duration of glucose-lowering activity of approximately 6 hours (comparable with RHI).⁴⁰ This is useful for patients reluctant to begin insulin therapy because of injections; however, you will need to closely monitor hypoglycemia.

TABLE
How to use sensitivity factors to calculate 24-hour insulin need

Characteristic	Dosage (U/kg)
Phenotype
Normal weight
Extremely physically active	0.3 baseline
Moderately physically active	0.4 baseline
Minimally active	0.5 baseline
Obese
Extremely physically active	0.5 baseline
Moderately physically active	0.6 baseline
Minimally active	0.8 baseline
Renal failure	Subtract 0.2
Coexisting illness raising risk of hypoglycemia	Subtract 0.2
Eating habits (“big eater”)	Add 0.1
New-onset type 1 diabetes, <30 years of age	0.3 baseline
Reprinted with permission from Leahy, Insulin Therapy 2002.²⁹

Basal-prandial insulin in new type 2 diabetes

In certain cases, it may be more appropriate to initiate insulin therapy using a basal-prandial regimen that includes injections of prandial insulin with each meal of the day. Such cases include patients with newly diagnosed type 2 diabetes who have A_1c levels >10.0%, or insulin-naive patients on oral antidiabetic drug regimens who have A_1c levels >8.5%.²⁵

FAST TRACK

Inhaled insulin is an appealing option for patients who are reluctant to begin insulin therapy because of the injections

You can calculate the starting total 24-hour insulin dosage for both the basal and prandial insulin components by multiplying body weight in kg by a factor based on the patient’s estimated insulin sensitivity ( TABLE ).²⁹