MD Conference Express - (Page 21)
Clinical Pearl Starting insulin therapy with a basal insulin regimen results in less weight gain and hypoglycemia than premixed insulin twice daily or prandial insulin with meals. In addition to starting insulin therapy, clinicians need to consider whether to prescribe analog or neutral protamine Hagedorn (NPH) insulin. An analysis from Mullins and colleagues evaluated the interaction between hypoglycemia and A1C, and rates of hypoglycemia in 11 Phase III and Phase IV clinical trials that compared the insulin analog glargine with NPH insulin in patients with either type 1 or T2DM.10 The rate of hypoglycemia increased with both regimens as A1C levels fell. However, glargine was associated with lower rates of hypoglycemia, both unadjusted and when modeled using the negative binomial distribution with the end-point A1C as a covariate. In the latter analysis, the rate of all symptomatic hypoglycemia was 9.1% (p<0.05), 26.6% (p<0.001) for confirmed hypoglycemia, and 30.0% (p=0.08) for severe hypoglycemia. Figure 2 demonstrates the lower frequency of hypoglycemia with the long-acting insulin analog than with NPH at each level of achieved A1C.10 Figure 2. Relationship of A1C to Hypoglycemia in T2DM.
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What change should be made to the patient’s therapy? The recommendation is to replace the NPH insulin with a long-acting insulin analog (glargine, or alternatively, detemir) also given at bedtime. The evidence for this change comes from an open-label, parallel, 24-week multicenter trial of 756 overweight men and women with inadequate glycemic control who received bedtime glargine or NPH once daily and one or two oral agents. The study found that while most patients (~60%) achieved an A1C ≤7% with each insulin type, nearly 25% more patients attained this level with no documented nocturnal hypoglycemia with glargine, and rates of other types of symptomatic hypoglycemia were 21% to 48% lower with glargine compared with those who were taking NPH insulin.11 After 3 months, the patient’s hypoglycemia has improved, but he still has a suboptimal A1C of 7.5%. The likely culprit is postprandial hyperglycemia. A study by Monnier and colleagues found that when the A1C is only moderately elevated, 70% of the contribution to the substandard A1C stems from postprandial glycema (Figure 3).12 Figure 3. Percent Contribution to A1C.
FPG 100 80
30% 60% 55% 50%
PPG
Percent Contribution
Hypoglycemia confirmed <65 mg/dl (events per 100 patient-years)
60 40 20 0
70%
150
70% 40% 45% 50%
100
NPH
30%
>10.2
10.2-9.3
9.2-8.5 A1C Range
8.4-7.3
<7.3
50 p=0.021 0
Glargine
Reproduced with permission from I. Blumer, MD.
7 8 A1C% 9 10
6
Conclusion While numerous algorithms and guidelines exist to guide clinicians in the appropriate management of patients with T2DM, a close examination of patients’ pre- and postprandial glycemic levels, as well as rates and timing of hypoglycemia, can provide important guideposts to selecting the most appropriate therapy. References
1. 2. Akalin S, Berntorp K, Ceriello A, et al. Int J Clin Pract. 2009;63(10):1421-1425. Eldor R, Raz I. Rev Diabet Stud. 2009;6(1):6-12. Holman RR, Paul SK, Bethel MA, et al. N Engl J Med. 2008;359(15):1577-1589. Holman RR, Paul SK, Bethel MA, et al. N Engl J Med. 2008;359(15):1565-1576. Rodbard HW, Jellinger PS, Davidson JA, et al. Endocr Pract. 2009;15(6):540-559. Skyler JS, Bergenstal R, Bonow RO, et al. J Am Coll Cardiol. 2009;53(3):298-304. The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med. 2008;358(24):2545-2559. Phung OJ, Scholle JM, Talwar M, et al. JAMA. 2010;303(14):1410-1418. Holman RR, Farmer AJ, Davies MJ, et al. N Engl J Med. 2009;361(18):1736-1747. Mullins P, Sharplin P, Yki-Jarvinen H, et al. Clin Ther. 2007;29(8):1607-1619. Riddle MC, Rosenstock J, Gerich J. Diabetes Care. 2003;26(11):3080-3086. Monnier L, Colette C, Dunseath GJ, et al. Diabetes Care. 2007;30(2):263-269. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
NPH is adequate when A1C goal is >8%. With lower goal, glargine or detemir may be preferable
Mullins P et al. Clin Ther. 2007.
Reprinted from Clinical Therapeutics; Mullins et al, 2007; with permission from Excerpta Medica.
Clinical Pearl Glargine causes less hypoglycemia than NPH insulin over a wide range of achieved A1C levels.
Case 3 The third case was presented by Ian Blumer, MD, University of Toronto, Ontario, Canada. The patient is a 65-year-old man who has had T2DM for 10 years. He has a BMI of 30 kg/m2 and an A1C level of 7.5% and is currently taking glimepiride 4 mg/day, metformin 1 g twice daily, and NPH insulin 25 units at bedtime. The patient is experiencing some nocturnal hypoglycemia.
Table of Contents for the Digital Edition of MD Conference Express
MD Conference Express
Contents
Real-Time Continuous Glucose Monitoring and Diabetes Treatment
The Globalization of Diabetes
Treat the Individual, Tend to the Population
Microvascular Outcomes from the ACCORD Trial
Diabetic Retinopathy in the ACCORD Trial
Results from the STAR 3 Study
Findings from HELP PD
Insights from the BARI 2D Trial
Effect of Atorvastatin on Beta Cell Function
Caffeine Supplementation Reduces Exercise Induced Hypoglycemia
Cardiometabolic Risk
Point of Care Devides
Newer Insulins
Diabetes, Glycemia and Cardiovascular Disease: Is it Time to Rethink the Regulatory Approach?
Diabetes and Cancer: ADA Consensus Statement
The Diabetic Foot Wound
HEALTHY Study - Middle School-Based Intervention to Reduce Diabetes Risk
MD Conference Express
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