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+ Diabetes Maureen McQueeney, PharmD, BCPS, BCACP, CDE.

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Presentation on theme: "+ Diabetes Maureen McQueeney, PharmD, BCPS, BCACP, CDE."— Presentation transcript:

1 + Diabetes Maureen McQueeney, PharmD, BCPS, BCACP, CDE

2 + Learning Objectives Describe each class of diabetic agents in detail including the following: efficacy, indications, advantages, adverse effects, contraindications and drug interactions. Be familiar with how the oral and injectable agents compare in terms of their effect on weight, the lipid profile, cost, HbA1c reduction and fasting plasma reduction. Demonstrate proper technique in preparing an insulin dose including the specific sequence of steps in mixing insulins where appropriate. Describe medications that may cause hypo/hyperglycemia and potential drug interactions

3 Pathophysiology of DM Glucagon  BG  BG

4 Pathophysiology of DM Glucagon  BG  BG, but feedback is that there is no glucose to tissue Little or no insulin secreted from pancreas Insulin not working at tissue receptors

5 +  Insulin from β -cells Blood glucose homeostasis Ingestion of food Pancreas  -cells  -cells  Glucagon from α -cells Glucose production by liver Glucose uptake by adipose and muscle tissue Release of gut hormones (Incretins: GLP-1 and GIP) Glucose-dependent GI Tract Merck Medicus. Accessed April10, For educational purposes only. DPP-IV Pathophysiology of DM 5 In type 2 DM--- GLP-1and GIP with loss of effect

6 + Diabetes Medications 6

7 + Patient Case #1 HPI: H.G is a 45 year old obese female who comes to your clinic for a follow-up on her blood results and to start a medication for her Type 2 DM. She refuses to start insulin at this point. PMH: Type 2 diabetes (recently diagnosed) Hypertension x 2 years, hyperlipidemia Medications: lisinopril 20 mg daily, hydrochlorothiazide 25 mg daily, aspirin 81 mg daily 7

8 + Patient Case #1 SH: Alcohol: (-), (-) Smoking All: NKDA PE: BP: 122/72, HR 77 Height: 5’5’’, Weight: 210 lbs, BMI: 35 Labs: FPG: 210 mg/dL; PPG: 200 mg/dL; HbA1c: 8.0%; Scr: 1.01; LFTs: WNLs 8

9 + Patient Case #1 Which of the following medications is the most appropriate initial medication for this patient? Before we answer---- lets talk about the options!!!! 9

10 + Biguanides 1 Medications Metformin (Glucophage ®) Metformin ER (Glucophage XR ®, Fortamet ER ®) Mechanism of action ↓ hepatic glucose production ↑ insulin sensitivity Effects ↓ A1c by 1.5% ↓ FPG 10

11 + Biguanides 1 Side effects Weight loss Transient N/V/D Lactic acidosis Contraindications/Precaution Males w/SCr ≥ 1.5; females w/SCr ≥ 1.4 Caution in pts over 80 years of age Additional comments May have positive effect on lipid profile ER formulation may be associated with less GI effects May be taken with food to decrease GI effects 11

12 + Sulfonylureas 1 Medications Glipizide (Glucotrol ®) Glipizide ER (Glucotrol XL ®) Glyburide (Micronase ®, Diabeta ®) Glimepride (Amaryl ®) Mechanism of action ↑ pancreatic beta cell insulin secretion in a glucose independent manner 12

13 + Sulfonylureas 1 Effects ↓ A1c by 1.5% ↓ FPG and PPG (mixed effect) Side effects Hypoglycemia Weight gain Additional comments Glyburide should not be used in CrCl < 50 ml/min Glipizide should be taken 30 minutes before meals Other agents should be taken with meals 13

14 + Short-Acting Secretagogues 1 Medications Repaglinide (Prandin ®) Nateglinide (Starlix ®) Mechanism of action ↑ pancreatic insulin secretion in a glucose-dependent manner Effects ↓ A1c by 0.6 – 1.5% ↓ PPG 14

15 + Short-Acting Secretagogues 1 Side effects Weight gain Hypoglycemia Additional comments Repaglinide more effective Less hypoglycemia than sulfonylureas Take before or with meals Repaglinide: immediately before or with meals Nateglinide:1-30 minutes prior to meals 15

16 + Glucagon-Like Peptide 1 Agonists 1,2 Medication Exenatide (Byetta ®) Liraglutide (Victoza®) Exenatide extended-release (Bydureon®) Mechanism of action ↑ glucose-dependent insulin secretion ↓ glucagon secretion ↓ gastric emptying ↑ satiety Effects ↓ A1c by 0.5 – 1.0% ↓ PPG 16

17 + Glucagon-Like Peptide 1 Agonists 1,2 Side effects N/V/D Weight loss Headache Pancreatitis Hypoglycemia Additional comments Subcutaneous injection Use with sulfonylureas: ↓ sulfonylurea dose by 50% due to risk of hypoglycemia Take up to 60 minutes prior to morning and evening meals 17

18 + Amylin Agonists 1,3 Medication Pramlintide (Symlin ®) Mechanism of action ↓ gastric emptying ↓ glucagon production ↑ satiety Effects ↓ A1c by 0.5 – 0.7% ↓ PPG 18

19 + Amylin Agonists 1,3 Side effects Nausea Anorexia Weight loss Hypoglycemia Additional comments Subcutaneous injection Use with insulin: ↓ meal time insulin by 50% due to risk of hypoglycemia Used in type 1 and 2 DM 19

20 + Dipeptidyl Peptidase 4 (DPP-4) Inhibitors 4-6 Medications Sitagliptin (Januvia ®) Saxagliptin (Onglyza ®) Linagliptin (Tradjenta®) Mechanism of action ↓ metabolism of incretin hormones Effects ↓ A1c by 0.62 – 0.85% ↓ PPG 20

21 + DPP-4 Inhibitors 4-6 Side effects Nasopharyngitis URI Headache Abdominal pain N/D Hypersensitivity Pancreatitis (with sitagliptin) Additional comments Use with sulfonylureas: ↓ sulfonylurea dose by 50% due to risk of hypoglycemi a 21

22 + DPP-4 Inhibitors 4-6 Renal adjustment Sitagliptin CrCl< 50 ml/min: 50 mg daily CrCl< 30 ml/min: 25 mg daily Saxagliptin CrCl< 50 ml/min: 2.5 mg daily Drug Interactions Saxagliptin is a CYP 3A4 substrate Caution with strong 3A4 inhibitors 22

23 + Back to Patient Case #1 HPI: HG is a 45 year old obese female who comes to your clinic for a follow-up on her blood results and start a medication for her Type 2 DM. She refuses to start insulin at this point. PMH: Type 2 diabetes (recently diagnosed) Hypertension x 2 years, Hyperlipidemia Medications: lisinopril 20 mg daily, hydrochlorothiazide 25 mg daily, aspirin 81 mg daily 23

24 + Back to Patient Case #1 SH: Alcohol: (-), (-) Smoking All: NKDA PE: BP: 122/72, HR: 77 Height: 5’5’’, Weight: 210 lbs, BMI: 35 Labs: FPG: 210 mg/dL; PPG: 200 mg/dL; HbA1c: 8.0%; Scr: 1.01; LFTs: WNLs 24

25 + Back to Patient Case #1 Which of the following medications is the most appropriate initial medication for this patient? A. Glipizide B. Sitagliptin C. Pioglitazone D. Metformin 25

26 + Patient Case #2 RE is a 75 year old female who was referred to you by her PCP for help with DM management. She was recently diagnosed with Type 2 DM. She has a history of CAD, hyperlipidemia, depression and HTN. Her current medications include: aspirin 81mg daily, Diovan 320 mg daily, Plavix 75 mg, ranitidine 150mg PO BID, NTG PRN, metoprololsuccinate 50 mg daily, Crestor 40 mg daily, Cymbalta 90 mg daily 26

27 + Patient Case #2 Allergies/intolerances: ACEIs - cough Vital signs: BP: 123/61, HR: 62, wt: 135 lbs, ht: 5’5”, Labs: A1c 7.9%, Scr 1.43, LFTs: WNLs, CrCl: 31 ml/min Social pearls Patient has Medicare Part D and is very concerned about reaching her the “donut hole” 27

28 + Patient Case #2 Which of the following is most appropriate initial treatment for this patients DM? A. Glyburide 2.5 mg PO BID B. Metformin 500 mg PO BID C. Saxagliptin 5 mg daily D. Glipizide 2.5 mg PO BID 28

29 + Insulin Therapy 29

30 + Insulin Therapy Medications Aspart (Novolog ®) Lispro (Humalog ®) Glulisine (Apidra ®) Regular (Humulin R ®, Novolin R ®) NPH (Humulin N ®, Novolin N ®) Glargine (Lantus ®) Detemir (Levemir ®) 30

31 + Insulin Therapy Medication (continued) Humalog Mix 75/25 ® 75% lispro protamine/25% lispro Humalog Mix 50/50 ® 50% lispro protamine/50% lispro Novolog Mix 70/30 ® 70% aspart protamine/30% aspart Humulin Mix 70/30 ® and Novolin Mix 70/30 ® 70% NPH/30% regular Humulin Mix 50/50 ® 50% NPH/50% regular 31

32 + Insulin Therapy 7 32

33 + Insulin Therapy 1 Mechanism of Action Exogenous administration of insulin Side effects Hypoglycemia Weight gain Additional comments Subcutaneous injection Most effective treatment Positive effect on HDL and TGs Glargine and detemir cannot be mixed 33

34 + Insulin Regimens 8 Nonphysiologic Insulin regimen 34

35 + Insulin Regimens 8 Physiologic insulin regimen 35

36 + Initiation of Insulin per ADA Guidelines 10 36

37 37

38 + Insulin Titration Treat-to-Target algorithm. 38

39 + Sliding Scale Insulin 13,14 Advantages Convenient and simple to initiate Patient involvement in his/her therapy Can be used to supplement scheduled insulin doses Disadvantages Not supported by clinical literature Treats hyperglycemia instead of preventing it Lag time to onset of insulin Poor glycemic control Patient adherence and competency required Not recommended in outpatient setting per ADA 39

40 + Adjusting Insulin Therapy 15 TypeInjection TimeAffected BG reading Rapid or Short- acting Before BreakfastBefore Lunch Before Supper 2-3 hrs after supper or bedtime Intermediate-acting or mixed insulin Before BreakfastBefore Supper Before Supper/Bedtime Before Breakfast (next morning) Long-acting Before BedtimeThroughout the day 40

41 + Converting Between Types of Insulin Types of InsulinRecommendation NPH to detemirConvert unit-per-unit Give detemir once daily or BID NPH to glargineNPH once daily: unit-per-unit give once daily NPH twice daily: added total NPH dose and reduce by 20% give once daily Detemir or glargine to NPH Convert unit-per-unit Give NPH at bedtime or BID Detemir to glargine or glargine to detemir Concert unit-per-unit Give once daily or BID if necessary 41

42 + Converting Between Types of Insulin Regimens 21 Regular to Rapid Total up daily dose then split between meals One basal injection → Add rapid-acting insulin at largest meal Give 10% of total daily dose as rapid-acting analog at largest meal Reduce basal dose by 10% Can give additional insulin injections before all meals if necessary 42

43 + Converting Between Types of Insulin Regimens 21 One basal injection → Two premix injections Divide total daily dose in half Give pre-breakfast and pre-supper premix insulin The largest meal requires a larger proportion of insulin Reduce total dose by 20% if recurrent hypoglycemia One premix injection → 2 premix injections Divide TDD in half Give before breakfast and dinner Reduce total dose by 20% if recurrent hypoglycemia 43

44 + Conversion Example Convert to physiologic regimen using Lantus and Humalog insulin InsulinAMPM NPH812 Regular610 44

45 + Conversion Example What should the total Lantus® dose be? A. 20 units B. 18 units C. 16 units D. 14 units What should the Humalog® dose be? A. 5 units before breakfast, lunch and dinner B. 5 units before breakfast and lunch and 6 units before dinner C. 8 units before breakfast and dinner D. 6 units before breakfast and 10 units before dinner 45

46 + Treatment Strategies 46

47 + Contributions of FPG and PPG to Overall A 1C 22 Post- Prandial Fasting Diabetes Care. 2003;26:

48 +

49 + AACE Treatment Guidelines 23 Monotherapy: HbA1c 6-7% Options: metformin, TZDs, secretagogues, DPP-4 inhibitors, alpha- glucosidase inhibitors Monitor and titrate every 2-3 months Consider combination therapy if goals not met after 2-3 months Combination therapy: HbA1c 6-7% Initiation/intensify combination therapy: A1c 8-10% Initiate/intensify insulin: A1c > 10% Consider basal-bolus insulin therapy: A1c > 8.5% 49

50 + Patient Case #3 HPI: AT is a 64 year old female with a history of Type 2 DM. She is reporting to clinic for evaluation of DM control. PMH: Type 2 DM since 2005, hyperlipidemia, depression and GERD Medications: metformin 1000 mg PO BID, glyburide 10mg PO BID, omeprazole 20 mg daily, Lipitor 20 mg daily 50

51 + Patient Case #3 Allergies: NKDA SH: (+) smoking: 1 ppd, occ ETOH Vital signs: BP: 149/58, HR: 60, Height: 63.5 in, Weight: 138 lbs BG per glucometer: FBG: 80s-110s, PPG: s 51

52 + Patient Case #3 Labs: A1c: 7.3% Scr: 0.71 LFTs: WNLs Total cholesterol: 138 Triglycerides 121HDL: 31 LDL: 83 Social pearls Patient refuses to start insulin therapy at this point despite extensive education regarding the benefits of insulin therapy. She is fearful of the injection and potential for weight gain. 52

53 + Patient Case #3 Which of the following treatment recommendations would be the most appropriate for this patient? A. Sitagliptin 100 mg daily B. Byetta 10 mcg SC before breakfast and dinner C. Nateglinide 60mg PO TID D. Pioglitazone 30 mg PO daily 53

54 + Patient Case #4 GR is a 57 year obese male with a PMH history of Type 2 DM, hyperlipidemia and HTN who reports to the clinic for a follow up on his DM management and to discuss weight loss options. Medications: metformin 850 mg PO TID, simvastatin 80 mg QHS, lisinopril 80 mg daily, diltiazem ER 360 mg daily, nefazodone 300mg PO BID Allergies: NKDA 54

55 + Patient Case #4 Vital signs: BP: 145/82, HR: 82, Weight: 300 lbs, Height 6’0”, BMI: 40.8 Labs: A1c 7.3%, Scr: 1.10; LFTs: WNLs BG per glucometer 55 DateBefore Breakfast2-hr post prandial 9/17/ /16/ /15/ /14/ /13/ /12/

56 + Patient Case #4 Which of the following is most appropriate recommendation for management of GRs DM? A. Byetta 5 mcg SC BID B. Saxagliptin 5 mg PO daily C. Humalog 4 units before largest meal D. Lantus 10 units QHS 56

57 + Patient Case #5 EM is a 54 year old male who was recently started on Lantus insulin. You were asked to make a recommendation regarding his diabetes regimen. He is currently taking metformin 1000mg PO BID, glyburide 10 mg PO BID and Lantus 38 units at bedtime (increased from 30 units last week), simvastatin 80mg QHS and lisinopril 20 mg daily 57

58 + Patient Case #5 BG per patient glucometer 58 DateBefore BreakfastBedtime 9/17/ /16/ /15/ /14/ /13/ /12/

59 + Patient Case #5 SH: (+) smoking: 1 ppd, occ ETOH Vital signs: BP: 130/58, HR: 60, Height: 67 in, Weight: 255 lbs Fasting Lipid panel Total Cholesterol: 148Triglycerides: 289 HDL: 30LDL: 65 Labs: A1c: 9.5%; Scr 1.13 mg/dL 59

60 + Patient Case #5 What is the most appropriate recommendation for this patients DM treatment? A. Increase Lantus insulin to 40 units B. Add Humalog 4 units before his biggest meal C. Increase Lantus insulin to 46 units D. Increase Lantus insulin to 44 units and add Humalog 4 units before breakfast and dinner 60

61 + Patient Case # 6 EM comes back to the clinic after several visits and his current diabetes regimen includes: metformin 1000mg PO BID, Lantus insulin 60 units QHS. Most recent labs A1c: 7.3% SCr: 1.13 mg/dL FPG s 61

62 + Patient Case #6 What would be the most appropriate recommendation at this time? A) Increase Lantus to 65 units B) Add Januvia 100 mg daily C) Advise patient to test BS before meals and at bedtime D) Add 10 units of Regular insulin before breakfast 62

63 + Patient Case #6 EM takes your advice and checks his BG before meals and at bedtime for the last week. 63 DateBefore BreakfastBefore LunchBefore DinnerBedtime Mon Tues Wed Thurs Fri Sat Sun

64 + Patient Case #6 What would be the most appropriate recommendation for EM at this time? Add Humalog 4 units before breakfast Add Apidra 4 units before lunch Add Novolog 4 units before dinner 64

65 + Insulin Administration

66 + ADMINISTRATION OF INSULIN Preparation of insulin using vial and syringe: Hands and injection should be cleaned Remove the cap on the insulin vial and sterilize the top with an alcohol swab If using NPH or mixed insulin roll gently between hands Do not shake vigorously Draw air into the syringe that is equal to the amount of insulin to be injected and push that air into the vial Draw up amount of insulin to be given Air bubbles not dangerous Can cause less dose to be injected

67 + ADMINISTRATION OF INSULIN Preparation of insulin by insulin pen device Hands and injection site should be cleaned Wipe the rubber seal on the pen body with an alcohol swab If using NPH or mixed insulin roll the pen gently between hands Do not shake Prime the pen by dialing to 2 units of insulin (do this with every use) Select the required dose by turning the dial until it reached the desired dose

68 + ADMINISTRATION OF INSULIN Subcutaneous technique Lightly grasp a fold of skin (“pinch an inch”) Inject at a 90° angle Release the skin fold Push the plunger down Wait at least 5 seconds after complete depression of plunger If painful, blood or clear fluid is seen after withdrawing the needle, apply pressure for 5-10 seconds without rubbing

69 + ADMINISTRATION OF INSULIN Rate of absorption: abdomen > arms > thighs > buttocks area

70 + MIXING OF INSULIN Column 1______________________Column 2 HumalogNPH NovologGlargine Regular Detemir Apidra

71 + QUESTIONS? 71

72 + References 1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2008;31: Byetta [package insert]. San Diego (NC): Amylin Pharmaceuticals, Inc and Eli Lilly and Company; Symlin [package insert]. San Diego (NC): Amylin Pharmaceuticals, Inc; Covey DF, Rodgers PT. New therapeutics options for improving glycemic control in patients with type 2 diabetes mellitus. 5. Januvia [package insert]. Whitehouse Station (NJ): MERCK & CO., INC.; Onglyza [package insert]. Princeton (NJ): Bristol-Myers Squibb; Lexi-Comp Online™, Hudson, Ohio: Lexi-Comp, Inc.; 2008; November 2, DeWitt DE, Dugdale DC. Using new insulin strategies in the outpatient treatment of diabetes. JAMA 2003;289(17): Dipiro JT, Wells BG, Schwinghammer TL, Hamilton CW. Pharmacotherapy handbook. 6 th ed. New York: McGraw-Hill, Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2008;31(12):1–11. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2008;31(12):1–

73 + References 11. Riddle MC, Rosenstock J, and 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(11): Unger Jeff. Management of Type 1 Diabetes. Prim Care Clin Office Pract. 2007; 34: Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin use: myth or insanity? The American Journal of Medicine 2007; 120: Hirsch IB, Farkas-Hirsch R. Sliding scale or sliding scare: it’s all sliding nonsense. Diabetes Spectrum 2001; 14(2): Carlise BA, Kroon LA, Koda-Kimble MA. Diabetes mellitus. In: Koda-Kimble MA, Young LY, Kradjan WA, Guglielmo BJ, editors. Applied therapeutics: the clinical use of drugs. 8 th edition. Philadelphia, PA: Lippincott Williams & Wilkins; Garber A, Wahlen J, Wahl T, et al. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (the 1-2-3). Diabetes Obes Metab. 2006; 8(1): Raskin P, Allen E, Hollander P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care. 2005;28(2): Levemir [package insert]. Princeton (NJ): Novo Nordisk Inc; Lantus [package inser]. Bridgewater (NJ): Sanofi-Aventis U.S. LLC; U.S. Food and Drug Administration. Information regarding storage and switching between products in an emergency. (accessed October 10, 2009) Hirsch IB, et al. A real-world approach to insulin therapy in primary care practice. Clinical Diabetes 2005; 23:

74 + References 22. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care. 2003; 26: Rodbard HW, Blonde L, Braithwaite SS, et al. American association of clinical endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract 2007;13 (supp 1):s Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB,Pasternak RC, Smith SC Jr, Stone NJ. Implications of recent clinical trials for theNational Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004 Jul 13;110(2): Cholesterol-lowering agents. Pharmacist's Letter/Prescriber's Letter 2006;22(8):

75 + Questions


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