Management of Type 2 Diabetes

1. Management of Type 2 Diabetes • Med-Peds Continuity Clinic • Baylor College of Medicine

2. Case • 50 yo male with Type II diabetes for the past 8 years. • Current medications: Glyburide 10mg po bid and Metformin 1000mg po bid • Last Hgb A1c 6 months ago was 7.5. • Today: Hgb A1c is 9.3 with a FBS of 250 mg/dl • You are confident he has been compliant with his therapy. What is your next step?

3. Oral Hypoglycemic Agents: MOA and Efficacy

4. Decline in β-cell function: UKPDS 25-30% initial non-responders to OHA 5-20% fail each year by 10-15 yrs, ~100% OHA failure

5. Oral Agents • Sulfonylurea efficacy declines with the progressive diminishing β-cell function. • Metformin and Glitazones can continue to provide some benefit throughout the course of the disease. • In order to adhere to ADA and ACE treatment goals, physicians should consider initiating insulin therapy at the first sign of poor response to oral agents. • In general, patients with A1c >10% need to be on insulin.

6. Barriers to Starting Insulin: Patient Driven • Fear of needles/injections and pain • Fear of hypoglycemia • Belief that once one starts insulin, they will soon die • Belief that starting insulin means the “disease has won” • Fear of insulin induced by the provider • “if you don’t start doing X, I’m going to have to put you on insulin”

7. Barriers to Starting Insulin: Provider Driven • Unsure how to start and how to adjust • Belief that patient compliance will be adversely affected • Fear of patient rejection • Concern for inducing side effects (hypoglycemia, weight gain)

8. Insulins and Duration of Action

9. Patient is on glucovance 5/500 2 tabs po bid. He has had DM II for 5 years. What is your next course of action? Initiate insulin therapy with BIDS therapy – ‘bedtime insulin, daytime sulfonylurea’

10. Bedtime insulin/Daytime Sulfonylurea (BIDS) General rules of thumb: Start with 10 units NPH qhs Administration is usually between 10 pm and midnight.

11. Titration of bedtime insulin

12. Pros/Cons of Insulin + Oral Agents • Pros • Decreased insulin dose • Potential for less hypoglycemia • Less intensive insulin regimens • Cons • Increased number of meds – decreased compliance • Potential for drug interactions • Potentially more costly

13. Patient is currently on BIDS therapy with glyburide10mg qam, metformin 1gm bid and NPH insulin 16 units qHS.What is your next course of action? Initiate NPH insulin twice daily and discontinue glyburide

14. Other options in basal insulin • Insulin glargine (Lantus) in place of NPH • Pros: • ease of use (once daily) • 35% lower incidence of hypoglycemia • Cons: • formulary restrictions/cost • NPH equally effective in compliant patients

15. Starting Insulin Only • Normal daily insulin secretion is 0.5 to 0.7 u/kg/day • Hence, starting insulin doses range from 0.3 to 1.0 u/kg/day, with the average being 0.5 to 0.8 u/kg/day. • Factors in choosing 24 hour insulin needs: physical activity level, weight, renal failure, coexisting illness, eating habits

16. Calculating 24-hour insulin needs

17. Insulin Adjustments • Ms. Smith is on NPH 40u/Reg 14u qam, Reg 10u before dinner and NPH 30u qhs. She has reported multiple daytime and nighttime episodes of hypoglycemia. You decide to change NPH to glargine. How do you convert NPH to glargine? • 80% of NPH dose = initial glargine dose or in this case 56 units

18. Algorithm for Metabolic Management of Type 2 Diabetes *Although 3 oral agents can be used, initiation and intensification of insulin therapy is preferred based on effectiveness and expense. Source: Diabetes Care 2006;29:1-10

19. Other goals for insulin therapy • Patients who no longer have β-cell function require a Basal-Bolus Insulin Regimen, i.e. NPH bid/glargine qd combined with short acting insulin premeals. • Premix insulins (70/30, 75/25, 50/50) are more difficult to adjust and hence less popular. Serves as a good option for patients resistant to more than two injections of insulin a day.

20. Common Patient Questions • How often should blood sugar be checked? • At least as often as an injection of insulin is given • Can insulins be mixed (in same syringe)? • NOT with Glargine • Always draw up Short Acting Insulin before intermediate acting • Remember: First draw up clear, then cloudy - short acting insulins are clear, long acting are cloudy (except glargine - is clear)

21. Common Patient Questions • What to do with insulin dose when NPO? • Continue glargine at same dose • Skip Short Acting Insulin • FBG level should not vary if the glargine dose is correct. • If using NPH – pt should take 50% of dose • Skip SAI

22. New Insulin Therapies • Exubera - inhaled insulin • no advantage over injectable insulin • will require monitoring with PFTs • New fast acting agents: glulisine (Apidra) • New intermediate to long acting (basal) insulin: detemir (Levemir)

23. Summary • Oral agents have limited efficacy which will wane over a period of time. • Insulin initiation should be considered in any patient without optimal control on multiple oral agents (i.e. A1c>7%). • Combination therapy of an oral agent with insulin is safe and effective. • Choosing and dosing an insulin formulation should take into account the patient’s profile.

24. References • Nelson SE, Palumbo PJ. Addition of Insulin to Oral Therapy in Patients with Type 2 Diabetes. The American Journal of Medical Sciences May 2006;331:257-63. • Hirsch IB. Insulin Analogues. The New England Journal of Medicine Jan 2005;352:174-83. • Nathan DM, et al. Management of Hyperglycemia in Type 2 DM: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care August 2006;29:1963-72.