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

By

George E. Dailey, MD

A stepped approach to postprandial hyperglycemia—including prandial insulin—is key.

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References

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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.

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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.

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Practice recommendations

A stepwise approach to antidiabetic therapy allows for the treatment to change in response to disease progression. This usually means beginning with oral agents and adding insulin as required (B).
Treatment strategies must address both fasting and prandial hyperglycemia because prandial hyperglycemia has been shown to be an independent risk factor for cardiovascular events and mortality (B).

Strength of recommendation (SOR)

Good-quality patient-oriented evidence
Inconsistent or limited-quality patient-oriented evidence
Consensus, usual practice, opinion, disease-oriented evidence, case series

More than 80% of patients with type 2 diabetes—including more than a third of patients with good metabolic control—have excessive postprandial hyperglycemia.¹ That’s unwelcome news for the 20 million Americans with type 2 diabetes, especially when you consider that post-prandial hyperglycemia is a strong independent risk factor for all-cause mortality and cardiovascular events.^2-5

To help our type 2 diabetes patients gain ideal control, we need to do at least 2 things better:

Measure and act on glycosylated hemoglobin (A_1c) levels.
Take a stepped approach to glycemic control, making full use of prandial insulin.

A_1clevels and the important role they play

Analysis of A_1c is the “gold standard” for monitoring glycemic control in patients with diabetes because it provides an indication of mean plasma glucose levels during the preceding 120 days.⁶ The relative contribution of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) to A_1c levels is a dynamic function of the extent of day-long hyperglycemia; FPG has a greater influence at higher A_1c levels and PPG has a predominant role at lower A_1c levels.⁷

The relationship between hyperglycemia, as measured by A_1c, and increased morbidity and mortality (including cardiovascular events) was demonstrated several years ago in the United Kingdom Prospective Diabetes Study (UKPDS).⁸ Interestingly, several studies have also found that fasting glucose levels alone are not a reliable predictor for hyperglycemia-related morbidity or mortality, whereas postprandial hyperglycemia, as noted in the introduction, is a strong independent risk factor for all-cause mortality and cardiovascular events.^2-5

Continued management of A_1c through tight control of both FPG and PPG may therefore improve patient long-term health outcomes. A_1c should be evaluated every 3 to 6 months, and appropriate changes to the patients’ treatment regimens should be made accordingly.

An algorithm for the stepwise approach

We typically use oral antidiabetic drugs typically are used as initial therapy for patients with newly diagnosed type 2 diabetes, especially those with initial A_1c levels of 6.0% to 8.0%.⁹ Three recent publications^10-12 provide an excellent analysis of the rationale for combination therapy to address multiple physiologic defects, as well as the relative efficacy of agents.

FAST TRACK

The ADA’s stepped approach begins with lifestyle interventions and oral agents, and progresses to insulin if glycemic goals are not met

In 2006 the American Diabetes Association (ADA) and the European Association for the Study of Diabetes published a consensus statement that presented an algorithm for the initiation and adjustment of type 2 diabetes therapy (Figure).¹³ In this evidence-and experience-based treatment algorithm, the authors emphasize the achievement and maintenance of normal glycemic goals, initiating therapy with lifestyle intervention and metformin (Glucophage), not delaying therapy and transitioning to new regimens when glycemic targets are not achieved, and adding insulin therapy early to the regimens of patients who are not meeting glycemic targets.^9,13

You may also consider newer therapeutic options not included in the ADA’s 2007 treatment guidelines.¹⁴ Incretin mimetics and dipeptidyl-peptidase IV (DPP-IV) inhibitors are 2 new classes of antidiabetic agents that are effective for patients with type 2 diabetes. (See “2 new classes of antidiabetic agents: Incretin mimetics and DPP-IV inhibitors” ^15-22) Most patients with type 2 diabetes will, however, eventually require insulin therapy to maintain optimal glycemic control.²³

Advancement to insulin therapy

Basal insulin replacement achieves glycemic control

The addition of once-daily basal insulin to oral antidiabetic drug regimens is a simple way to introduce insulin therapy and achieve glycemic control. (See “A guide to basal insulin dosing and titration”^14,24-28)

In a randomized, parallel, multi-center study, treatment with once-daily insulin glargine (Lantus) or neutral protamine Hagedorn (NPH) insulin (Humulin, Novolin) added to preexisting oral antidiabetic drug regimens for 756 patients with inadequately controlled type 2 diabetes (A_1c >7.5%) effectively achieved the goal A_1c of ≤7.0% for most patients. More patients in the insulin glargine group were able to reach goal without experiencing any nocturnal hypoglycemia, compared with those in the NPH group (33.2% vs 26.7%, P<.05).²⁴
A similar study used a forced-titration algorithm to compare NPH insulin with insulin detemir (Levemir).²⁶ This study demonstrated that a similar reduction in A_1c could be achieved with insulin detemir and NPH insulin over 24 weeks (1.8% and 1.9%, P=ns), but weight gain and nocturnal hypoglycemia incidence were significantly lower with insulin detemir compared with NPH insulin (1.2 kg vs 2.8 kg, and 160 vs 349 events, respectively, P<.001 for both).