Britni Hebert, MD PGY-1

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1 Britni Hebert, MD PGY-1

2 Importance of Diabetes treatment Types of treatment Comparison of treatment/article Review Summary Example cases

3

4 1 out of 13 Americans have diabetes Complications include blindness, renal failure, limb amputation, stroke, heart disease Annually $1.74 Billion Most importantly, aggressive intervention decreases complication rate.

5 DCCT (Diabetes Complications and Control Trial) Effects of intensive glycemic control Reduction in complication Increase in hypoglycemic events UKPDS(United Kingdom Prospective Diabetes Study) Intensive glycemic control, effect on microvascular complications ** ACCORD & ADVANCE trials Annals of IM, Oct 2008, Editorial: Newer Insulins in Search of a Niche

6

7 Importance of Diabetes treatment Types of treatment Comparison of treatment/article Review Summary Example cases

8 Diet, exercise and weight loss Oral antidiabetics Biguanides: Metformin Sulfonylureas: chlorpropamide, tolazamide, glipizide, glimepiride Meglitinides: repaglinide, nateglitinide Alpha-glucosidase: acarbose, miglitol Thiazolidinediones: rosiglitazone, pioglitazone Insulin

9 An option following failure on oral medication(s) Preferred for HbA1c >9 despite metformin First line? Suspected late onset DM type I Low insulin levels Hepatic or renal disease Initial A1c >10

10 If after: HbA1 c Add Basal Insulin 1 OAD >9.0 2 OAD >8.0 3OAD >7.0 Nathan DM, et al. Diabetes Care. 2006;29(8):

11 Mealtime Basal

12 Rapid Acting Humalog (Lispro), NovoLog (Aspart) Onset: 15 minutes Peak: minutes Duration: 3-5 hours

13 Short Acting / Regular Humilin R, Novolin R Onset: minutes Peak: minutes Duration: 5-8 hours

14 Intermediate Acting / NPH HumilinN, NovolinN Onset: 1-3 hours Peak: 8 hours Duration: 20 hours HumilinL, NovolinL Onset: hours Peak: 7-15 hours Duration: hours

15 Long Acting Ultralente Onset: 4-8 hours Peak: 8-12 hours Duration: 36 hours Lantus (Glargine), Levemir (Detemir) Onset: 1 hour Peak: none Duration: 24 hours

16 Pre-mixed insulin Humulin 50/50 (NPH/regular) Humulin 70/30 (same) Humalog Mix 75/25 (lispro protamine/ lispro) Humalog Mix 50/50 (same) Novolin 70/30 (NPH/regular) Novolog Mix 70/30 (aspart protamine/ aspart)

17 Importance of Diabetes treatment Types of treatment Comparison of treatment/article Review Summary Example cases

18 Article Review: Annals of Internal Medicine, Oct 2008, Comparative Effectiveness and Safety of Premixed Insulin Analogues in Type 2 Diabetes What Who How Results Problems

19 Meta-analysis reviewing 45 studies 43 RCT s 20 crossover studies 2 observational studies End points assessed Intermediate Outcomes Fasting glucose Postprandial glucose HbA1c Adverse outcomes Hypoglycemic events Weight gain Clinical Outcomes: death Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

20 Male predominance (52%) Average HbA1c 8.9 ( ) Average Duration of Dx: 11 years BMI Age yo Insulin naïve as well as previous users Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

21 Excluded: Diabetic complications Cardiac Disease Renal Disease Hepatic Disease Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

22 2 independent assessors Mean differences Odds ratio vs rate ratio Measured inconsistency between trials Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

23 Premixed Insulin Analogues vs Long Acting Analogues Higher fasting glucose (12 mg/dl) Lower Postprandial glucose (-27) Lower HbA1c (-0.39%) More hypoglycemic events (OR 2) More weight gain (2 kg) Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

24 Premixed Analogues vs Premixed Human insulin Fasting glucose insignificantly higher (4 mg.dl) Lower postprandial HbA1c equal Equal hypoglycemic episodes Equal weight gain Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

25 Premixed analogue vs Noninsulin Antidiabetics Lower fasting (-20) Lower postprandial (-37) Lower HbA1c (-0.5) More minor hypoglycemic events (OR 4.6) Equal major hypoglycemic events More weight gain (2.3kg) Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

26 Premixed Analogues vs All Other Tx All Cause Mortality: equal CV Mortality: equal CV Morbidity: equal Microvascular events: insufficient data ** Insignificant trend** Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

27 Funding of reviewed studies Publication bias Blinding Lack of clinical outcome Rehan, Shari; Annals of IM, Oct 2008, Vol 149, Issue 8

28 Importance of Diabetes treatment Types of treatment Comparison of treatment/article Review Summary Example Cases

29 Premixed Insulin Analogues Good for convenience, lowering HbA1c, postprandial glucose Worse for weight gain, hypoglycemic events, cost Clinical outcomes unclear More expensive No SSI Not flexible Annals of IM, Oct 2008, Editorial: Newer Insulins in Search of a Niche

30 Importance of Diabetes treatment Types of treatment Comparison of treatment/article Review Summary Example cases

31 75 yo M presents with an HbA1c of 9. He has been tried on several oral antidiabetics without success. He is otherwise healthy and walks with a cane. He sometimes forgets to eat meals. Which regimen of insulin would be best?

32 A 35 yo F presents with high postprandial sugars. She is currently taking NPH 20 units BID. She is reticent to adding more shots to her regimen. What might be an appropriate change to her current regimen?

33 Editorial: Newer Insulinsin Search of a Niche; Annals of IM, Oct 2008, Vol149, Issue 8. ulin.html cle.asp?id=5517 Systematic Review: Comparative Effectiveness and Safety of Premixed Insulin Analogues in Type 2 Diabetes; Rehan, Shari; Annals of IM, Oct 2008, Vol149, Issue 8.

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