Insulin for type 2 diabetes: How and when to get started

,

Applied Evidence

Insulin for type 2 diabetes: How and when to get started

J Fam Pract. 2014 February;63(2):76-81

By

Jay H. Shubrook, DO, FAAFP, FACOFP

With guidelines now calling for initiation of basal insulin for patients who are not at goal a year after diagnosis, familiarity with optimal timing, dosing, and titration is critical for family physicians.

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References

1. 2011 CDC National Diabetes Fact Sheet. Centers for Disease Control and Prevention Web site. Available at http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed January 3, 2014.

2. UKPDS Group. Intensive blood glucose control with sulphonylurea or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.

3. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE Comprehensive Diabetes Management Algorithm 2013. Endocr Pract. 2013;19:327-336.

4. Inzucchi SE, Bergenstal RM, Buse JB, et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient centered approach. A position statement of the ADA and the EASD. Diabetes Care. 2012;35:1364-1379.

5. Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Diabetes Care. 2004;27:1535-1540.

6. Shah BR, Hux JE, Laupacis A, et al. Clinical inertia in response to inadequate glycemic control. Diabetes Care. 2005;28:600-606.

7. Parchman ML, Wang CP. Initiation of insulin among veterans with type 2 diabetes and sustained elevation of HbA1c. Primary Care Diabetes. 2012;6:19-25.

8. Peyrot M, Rubin RR, Lauritzen T, et al. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care. 2005;28:2673-2679.

9. Polonsky WH, Hajos TR, Dain MP, et al. Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large international trial. Curr Med Res Opin. 2011;27:1169-1174.

10. Kunt T, Snoek FJ. Barriers to insulin initiation and intensification and how to overcome them. Int J Clin Pract Suppl. 2009;(164):6-10.

11. Presswala LS, Shubrook JH. Intensive insulin therapy as the primary treatment of type 2 diabetes. Clin Diabetes. 2011;29:151-153.

12. Li, C, Ford ES, Zhao G, et al. Trends of insulin use among US adults with type 2 diabetes: the Behavioral Risk Factor Surveillance System, 1995-2007. J Diabetes Complications. 2012;12:17-22.

13. Monthly Prescribing Reference (MPR). Insulin. Available at: http://www.empr.com/insulins/article/123739/. Accessed January 10, 2014.

14. Monami M, Marchionni N, Mannucci E. Long acting insulin analogs vs. NPH human insulin in Type 1 diabetes. A metaanalysis. Diabetes Obes Metab. 2009;11:372-378.

15. Goodrx Web site. Available at: www.goodrx.com. Accessed January 4, 2014.

16. LaSalle JR, Berria R. Insulin therapy in type 2 diabetes: a practical approach for primary care physicians and other health professionals. J Am Osteopath Assoc. 2013;113:152-162.

17. Davies M, Storms F, Shutler S, et al; ATLANTUS Study Group. Improvement of glycemic control in subjects with poorly controlled type 2 diabetes: comparison of two treatment algorithms using insulin glargine. Diabetes Care. 2005;28:1282-1288.

18. Accurate Insulin Decisions. The Endocrine Society Web site. Available at: http://www.accurateinsulin.org/. Accessed January 4, 2014.

19. Keating GM. Insulin degludec and insulin degludec/insulin aspart: a review of their use in the management of diabetes mellitus. Drugs. 2013;73:575-593.

20. Bergenstal RM, Rosenstock J, Arakaki RF, et al. A randomized, controlled study of once –daily LY2605541, a novel long acting basal insulin, versus insulin glargine in basal Insulin treated with patients in type 2 diabetes. Diabetes Care. 2012;35:2140-2147.

21. Hirsch LJ, Gibney MA, Li L, et al. Glycemic control, reported pain and leakage with a 4 mm × 32 G pen needle in obese and non-obese adults with diabetes: a post hoc analysis. Curr Med Res Opin. 2012;28:1305-1311.

PRACTICE RECOMMENDATIONS

› Initiate insulin for patients whose hemoglobin A1c ≥8% despite taking 2 or more oral agents. C
› Prescribe insulin for patients who have not reached their goal one year after diagnosis and initiation of oral therapy. C
› Consider reducing—but do not discontinue—oral agents, such as sulfonylureas and meglitinides, when you initiate insulin therapy. B

Strength of recommendation (SOR)

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

With type 2 diabetes now affecting 8.3% of the US population, most primary care physicians see patients with this disorder every day.¹ Based on the concurrent obesity epidemic, aging population, and emergence of type 2 diabetes in children and adolescents, it is estimated that by 2050, the prevalence will have risen from one in 12 Americans to one in 3.¹

Type 2 diabetes is a progressive disorder, with a relentless decline in beta cells. By the time of diagnosis, patients typically have lost at least 50% of insulin secretion; within 6 years of diagnosis, insulin secretion decreases to less than 25%.²

The American Association of Clinical Endocrinologists (AACE)³ and the American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD)⁴ have recently published guidelines for the management of type 2 diabetes. While the AACE’s guidelines (available at https://www.aace.com/files/aace_algorithm.pdf) focus on different treatments at different stages of disease and both glycemic and nonglycemic benefits of treatment,³ the ADA/EASD’s guidelines (see http://care.diabetesjournals.org/content/early/2012/04/17/dc12-0413.full.pdf+html) emphasize a patient-centered approach, shared decision making, and individualization of treatment goals based on both patient preference and comorbid disease states.⁴

One thing both sets of guidelines have in common is a purposeful intensification of therapy every 2 to 3 months, as needed, and the introduction of insulin one year after diagnosis if the patient is still not at goal.^3,4 But all too often, this does not occur, particularly in primary care settings.

This article will review the “when” and “how” of insulin initiation. But first, a look at barriers to insulin therapy and evidence in support of earlier use.

Clinical inertia and patient fear are associated with delays

Both the AACE and the ADA/EASD guidelines agree that metformin is best used as early as possible.^5,6 With typical use, however, metformin fails to prevent the progression of diabetes, as measured by the climb of hemoglobin A1c (HbA1c), at a failure rate of about 17% of patients per year.⁵ Physicians have been slow to intensify treatment for type 2 diabetes⁶—a phenomenon referred to as clinical inertia. In a recent study, patients were out of control—with an HbA1c >8%—for an average of 4.6 years before insulin was initiated.

Typically, physicians adopt a stepwise approach, which often results in patients spending more than 10 years with an HbA1c >7% and 5 years with an HbA1c >8% before insulin is started.⁵ In a recent Veterans Administration study, patients were out of control, with an HbA1c >8%, for an average of 4.6 years before insulin was initiated.⁷

Both patient and physician factors contribute to the delay. Patient factors include the fear of injection, the belief that insulin will interfere with their lifestyle, and the idea that the use of insulin signifies impending complications or even death.⁸ But such beliefs are starting to change. In a recent multinational study of patients with type 2 diabetes, less than 20% stated they were unwilling to start insulin.⁹

For their part, primary care physicians are much less likely to prescribe insulin than clinicians specializing in diabetes.⁶ Physician-reported barriers to insulin initiation include the time required to train patients to use it correctly; the lack of support, including access to diabetes educators; and the absence of clear guidelines on the use of insulin.¹⁰

A case for earlier insulin

There has been recent momentum in favor of earlier initiation of insulin. In fact, some researchers regard intensive insulin as an excellent first treatment for type 2 diabetes,¹¹ based on the belief that early insulin (used for a brief time) can provide not only immediate improvement in glucose control, but also a lasting “legacy” effect. The ADA/EASD guidelines support the use of insulin as a first-line treatment for patients with symptoms of insulin deficiency,⁴ but do not recommend it for everyone with newly diagnosed type 2 diabetes.

Primary care physicians are much less likely to prescribe insulin than clinicians specializing in diabetes.There have also been a number of advances in insulin therapy over the past 2 decades. These include insulin analogs with physiologic profiles that better match daily schedules, as well as improvements in the way insulin is delivered. Insulin pens, smaller needles, disposable devices, and insulin pumps have made it easier to administer and fine-tune insulin delivery. Despite these improvements and recommendations for earlier implementation, the use of insulin in type 2 diabetes is significantly lower today than in the 1990s.¹²