Type 2 diabetes: The role of basal insulin therapy

,; ,; ,; ,

Practice Alert

Type 2 diabetes: The role of basal insulin therapy

J Fam Pract. 2004 March;53(3):215-222

By

Derek Leroith, MD, PhD, FACP

Claresa S. Levetan, MD, FACE

Irl B. Hirsch, MD

Matthew C. Riddle, MD

PDF Download

References

1. American Diabetes Association. Economic costs of diabetes in the U.S. in 2002. Diabetes Care. 2003;26:917-932.

2. National Institute of Diabetes and Digestive and Kidney Diseases. National diabetes statistics fact sheet: general information and national estimates on diabetes in the United States, 2000. Bethesda, Md: U.S. Department of Health and Human Services, National Institutes of Health, 2002. National Institute of Diabetes and Digestive and Kidney Diseases, 2002.

3. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-234.

4. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003;289:2254-2264.

5. Dagogo-Jack S, Santiago JV. Pathophysiology of type 2 diabetes and modes of action of therapeutic interventions. Arch Intern Med. 1997;157:1802-1817.

6. Stratton IM, Adler AI, Neil HAW, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Br Med J. 2000;321:405-412.

7. Gaede P, Vedel P, Parving H-H, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno-2 randomised study. Lancet. 1999;353:617-622.

8. Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-393.

9. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br Med J. 1998;317:703-713.

10. American Diabetes Association. Clinical practice recommendations 2003. Diabetes Care. 2003;26(suppl 1):S1-S156.

11. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

12. National Institutes of Health, National Heart Lung and Blood Institute. JNC 7 Express: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, Md: US Dept of Health and Human Services; May 2003. NIH publication 03-5233. Available at: http://www.nhlbi.nih.gov/guidelines/hypertension/express. Accessed November 14, 2003.

13. American Association of Clinical Endocrinologists medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management: 2000 update. Endocr Pract. 2000;8(suppl 1):40-82.

14. Woolf SH, Davidson MB, Greenfield S, et al. Controlling blood glucose levels in patients with type 2 diabetes mellitus: an evidence-based policy statement by the American Academy of Family Physicians and American Diabetes Association. J Fam Pract. 2000;49:453-460.

15. National Committee for Quality Assurance. The State of Health Care Quality: 2003. Washington, DC: NCQA; 2003;1-34.

16. Saaddine JB, Engelgau MM, Beckles GL, Gregg EW, Thompson TJ, Venkat Narayan KMV. A diabetes report card for the United States: quality of care in the 1990s. Ann Intern Med. 2002;136:565-574.

17. Suwattee P, Lynch JC, Pendergrass ML. Quality of care for diabetic patients in a large urban public hospital. Diabetes Care. 2003;26:563-568.

18. Fleming BB, Greenfield S, Engelgau MM, Pogach LM, Clauser SB, Parrott MA. The Diabetes Quality Improvement Project: moving science into health policy to gain an edge on the diabetes epidemic. Diabetes Care. 2001;24:1815-1820.

19. American Diabetes Association. Screening for type 2 diabetes. Diabetes Care. 2004;27:S11-S14.

20. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: recommendations and rationale. Ann Intern Med. 2003;138:212-214.

21. Genuth S, Alberti KG, Bennett P, et al. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26:3160-3167.

22. Centers for Disease Control and Prevention. Prevalence of diabetes and impaired fasting glucose in adults: United States, 1999-2000. Morb Mortal Wkly Rep. 2003;52:833-837.

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

24. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854-865.

25. Feld S. AACE diabetes guidelines. Endocr Pract. 2002;8(suppl 1):41-65.

26. Wright A, Burden AC, Paisey RB, Cull CA, Holman RR. 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.

27. Riddle MC. The underuse of insulin therapy in North America. Diabetes Metab Res Rev. 2002;18:S42-S49.

28. Rosenstock J. Insulin therapy: optimizing control in type 1 and type 2 diabetes. Clin Cornerstone. 2001;4:50-64.

29. Avilés-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131:182-188.

30. Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes. Diabetes Care. 2000;23:639-643.

31. Yki-Jarvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care. 2000;23:1130-1136.

32. Riddle MC, Rosenstock J, Gerich J. 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.

33. Scarlett JA, Gray RS, Griffin J, Olefsky JM, Kolterman OG. Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes Care. 1982;5:353-363.

34. Malmberg K. and the DIGAMI (Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction) Study Group Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. Br Med J. 1997;314:1512-1515.

35. Hunt LM, Valenzuela MA, Pugh JA. NIDDM patients’ fears and hopes about insulin therapy: the basis of patient reluctance. Diabetes Care. 1997;20:292-298.

36. Fritsche A, Schweitzer MA, Haring HU. Glimepiride combined with morning insulin glargine, bedtime neutral protamine Hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2003;138:952-959.

37. Lepore M, Pampanelli S, Fanelli C, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000;49:2142-2148.

38. Full U.S. Prescribing Information for Lantus. Available at: http://www.lantus.com/professional/home.jsp .Accessed March 5, 2003.

39. DeWitt DE, Dugdale DC. Using new insulin strategies in the outpatient treatment of diabetes: clinical applications. JAMA. 2003;289:2265-2269.

40. Rosenstock J, Schwartz SL, Clark CM, Jr.,, Park GD, Donley DW, Edwards MB. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care. 2001;24:631-636.

41. Raut M, Sung JCY, Law AW. Cost of treating hypoglycemia among patients with diabetes [abstract]. Diabetes Care. 2003;26(suppl 2):A1152.-

Disclosures: Dr LeRoith serves as a consultant to Aventis Pharmaceuticals, Pfizer Inc, and Novo Nordisk Pharmaceuticals, Inc. and on the speakers’ bureaus of Aventis Pharmaceuticals, Pfizer Inc, and Eli Lilly and Co. Dr Levetan serves as a consultant to Eli Lilly and Co. and Novo Nordisk Pharmaceuticals, Inc. and on the speakers’ bureaus of Aventis Pharmaceuticals and Novo Nordisk Pharmaceuticals, Inc. Dr Hirsch serves as a consultant to Eli Lilly and Co., Novo Nordisk Pharmaceuticals, Inc., Aventis Pharmaceuticals, and Medtronic MiniMed. Dr Riddle has received grant/research support from Amylin Pharmaceuticals, Aventis Pharmaceuticals, and Pfizer Inc. He serves as a consultant to and is on the speakers’ bureaus of Amylin Pharmaceuticals, Aventis Pharmaceuticals, GlaxoSmithKline, and Novo Nordisk Pharmaceuticals, Inc. Corresponding author: Derek Le Roith, MD, PhD, Room 8D12, Bldg 10, National Institutes of Health, MSC 1758, Bethesda MD 20892-1758. E-mail: leroith@comcast.net.

Practice Recommendations

Patients should be screened for diabetes at age 45 years—earlier if they are overweight and have at least 1 other risk factor.
Management of type 2 diabetes requires a multifactorial approach that includes not only glycemic control but also addresses such risk factors as hypertension, dyslipidemia, renal impairment, and obesity.
Tight glucose control (A1C <7%) may require intensive therapy with more than one antiglycemic agent. Early addition of basal insulin may be an efficient way to achieve A1C targets in some patients.

According to the latest estimates by the American Diabetes Association (ADA), more than 12.1 million persons in the United States have been diagnosed with diabetes and about 6 million remain undiagnosed.¹ Type 2 diabetes, which comprises the majority (up to 95%) of all diabetes cases,² has a profound impact on patient health and quality of life and places significant burdens on the health care system. For example, it confers a risk for myocardial infarction (MI) and cardiovascular mortality that is comparable to that for patients who have previously had an MI.³

Economically, the costs of diabetes in the United States are overwhelming: direct and indirect medical expenditures related to diabetes totaled $132 billion in 2002 and are expected to increase to $192 billion annually by 2020.¹ Demographically adjusted, per-capita expenses for persons diagnosed with diabetes are more than double those of persons without diabetes.¹

Clinical challenge

Type 2 diabetes poses a major challenge to primary care physicians, who are the main providers of care for about 80% of patients with this disease.⁴ Patients may present with a variety of complications, including neurologic, peripheral vascular, cardiovascular (eg, MI, stroke), renal, and ophthalmic disorders.¹ Often, both microvascular and macrovascular complications precede the initial diagnosis of diabetes.⁵

Results of randomized clinical trials and population-based studies confirm that secondary preventive measures (ie, ameliorating risk factors in patients with known diabetes) and improved glycemic control can help reduce diabetes complications.^3,6 A multifactorial approach that both achieves glycemic control and addresses other risk factors, such as dyslipidemia, hypertension, and microalbuminuria, has been demonstrated to be important, particularly for reducing macrovascular complications.^7-9 Treatment goals for patients with type 2 diabetes include: an A1C value of <7.0%, a low-density lipoprotein cholesterol level of <100 mg/dL, and a blood pressure level of <130/80 mm Hg.^10-12

The United Kingdom Prospective Diabetes Study (UKPDS 35)—in a posthoc observational substudy—suggested that there is “no threshold” for A1C lowering for any type of diabetes complication, indicating that treatment probably should aim to bring the A1C level as close to normal as possible.⁶ Thus, the American College of Endocrinology (ACE), for example, has set an even more aggressive A1C goal of ≤6.5%.¹³ Organizations such as the ADA and ACE believe that lower A1C targets not only are beneficial but that they also are achievable with currently available therapeutic agents. Ultimately, an individual patient’s comorbid conditions, life expectancy, and preferences must be considered when determining goals.¹⁴

Despite compelling outcomes data, the prevalence of diabetes remains high and clinical control remains suboptimal. The Health Plan Employer Data and Information Set, a widely used tool for measuring quality of health care, currently considers an A1C of >9.5% as “poorly controlled” disease.¹⁵ According to data from the Third National Health and Nutrition Examination Survey, 18% of patients with diabetes have an A1C of >9.5%.¹⁶ In areas where obesity is highly prevalent, such as New Orleans, the percentages are even higher, with up to 43% of obese patients treated at urban teaching hospitals in that area having A1C values of >9.5%.¹⁷ The Diabetes Quality Improvement Project, which governs 20 public and private health care organizations, found that 35% of its patients had a mean A1C of >9.5%.¹⁸ Considering that 9.5% is well above the ADA goal of <7.0%, data such as these underscore the need for more widespread diabetes screening and earlier intervention.

Identifying diabetes

The ADA recommends that screening with a fasting plasma glucose test be considered in all patients aged 45 years and older, particularly those with a body mass index of 25 kg/m² or more.¹⁹ If the results are normal, screening should be repeated every 3 years. However, patients who are thought to be at increased risk should be considered for more frequent screening. The ADA recommendations have been endorsed by the American Academy of Pediatrics. The American Academy of Family Physicians follows the recommendations established by the US Preventive Services Task Force: screening is suggested in adults with hypertension or dyslipidemia.²⁰