9/29/14. Disclosures. Nothing to disclose

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1 Disclosures Nothing to disclose 1

2 Pharmacist Objectives 1. Select individualized glucose goals for patients with type 2 diabetes 2. List advantages and disadvantages of various classes of medications used to treat type 2 diabetes 3. Select ideal therapeutic agents using patient specific characteristics Technician Objectives 1. Understand what an A1C measures and how it relates to blood glucose 2. Recognize A1C and blood glucose values that are elevated for most patients 3. Recognize medications from various classes used to treat type 2 diabetes 2

3 Discuss personalization of diabetes management Individualized recommendations for glucose goals, lifestyle modifications and pharmacotherapy Type 2 Diabetes Mellitus Metabolic disease characterized by high blood glucose Risk factors Overweight/obese Family history Ethnicity Gestational diabetes Hypertension Hyperlipidemia 3

4 Estimates of Diagnosed Diabetes among Adults aged 20 years 4

5 Diagnose and assess control of diabetes Percent hemoglobin in red blood cells that is glycated Estimate of average glucose over previous 2-3 months ADA AACE A1C <7.0% 6.5% Preprandial glucose mg/dl <110 mg/dl Postprandial glucose <180 mg/dl <140 mg/dl Diabetes Care 2014;37(Suppl. 1):S14- S80. Endocr Pract. 2011; 17 (Suppl. 2):

6 Glucose Goals Individualized based on: Duration of disease Age/life expectancy Presence of comorbid conditions or advanced complications Ex. CVD, CKD Hypoglycemia unawareness Individual patient considerations Diabetes Care 2014;37(Suppl. 1):S14- S80 Hemoglobin A1C Goal A1c < 7% is appropriate for most patients Shown to reduce development of microvascular complications More stringent goals (ex. <6.5%) appropriate for some patients Achieved without significant hypoglycemia or ADR s Short duration of diabetes Long life expectancy No significant CVD Less stringent goals (ex. <8%) appropriate for some patients Long duration of disease Shorter life expectancy Presence of multiple chronic comorbidities or complications such as CVD Diabetes Care 2014;37(Suppl. 1):S14- S80 6

7 Diabetes Care 2014;37(Suppl. 1):S14- S80 Glucose Goals in Elderly Diabetes Care 2014;37(Suppl. 1):S14- S80 7

8 Legacy Effect United Kingdom Prospective Diabetes Study (UKPDS) 5100 patients with newly diagnosed type 2 diabetes followed for 10 years Intensive glucose control versus conventional Intensive groups: sulfonylurea/insulin Conventional group: diet alone Results A1c 7.0% in intensive group vs 7.9% in conventional group 12% reduction (95% CI 1-21, p=0.029) in any diabetes- related endpoint Mainly due to 25% risk reduction (7-40, p=0.0099) in microvascular endpoints 16% reduction (P=0.052) in myocardial infarction 10% reduction (- 11 to 27, p=0.34) in any diabetes- related death 6% reduction (- 10 to 20, p=0.44) in all- cause mortality Legacy Effect UKPDS Post- Trial Monitoring Additional 10 year follow- up A1c levels between groups converged by end of first year Results Significant risk reduction in intensive control groups versus conventional group after 10 years Any diabetes- related end point (9%, P=0.04) Microvascular disease (24%, P=0.001) Myocardial infarction (15%, P=0.01) Death from any cause (13%, P=0.007) Holman, et al. N Engl J Med 2008;359:

9 Legacy Effect Tighter glucose control early on is beneficial in the long run even if control is not sustained! JL is a 42 y/o HM who was diagnosed with type 2 diabetes 8 months ago. PMH: T2DM, HTN Current meds: metformin 1000mg twice daily, lisinopril 10mg daily Labs: BP 128/76 P 78 Ht 5 5 Wt 171 BMI 28.5 Na 139 K 4.5 Cl 102 SCr 0.9 egfr >90 BUN 23 AST 17 ALT 19 Glu 233 A1C 7.8% What A1C goal would you recommend for JL? 9

10 Case 2 SH is 67 y/o female who was diagnosed with type 2 diabetes 10 years ago. She checks her blood glucose once daily. Her diet mainly consists of southern foods and sweets but she reports trying to cut back on refined carbohydrates. Her exercise is limited by SOB but she has begun doing chair exercises 2-3x per week. PMH: CAD, HTN, T2DM, sleep apnea, depression Current meds: metformin 500mg twice daily, atorvastatin 40mg daily, losartan 100mg daily, ranolazine 500mg twice daily, fluoxetine 20mg daily Labs: BP 132/78 P 73 Ht 5 3 Wt 240 BMI 42.5 Na 135 K 4.5 Cl 101 SCr 1.11 egfr 51 BUN 23 AST 17 ALT 19 Glu 233 A1C 8.5% What A1C goal would you recommend for SH? Lifestyle Modifications Weight loss Tobacco cessation Moderation of alcohol Physical activity Medical nutrition therapy Diabetes Care 2014;37(Suppl. 1):S14- S80 10

11 Physical Activity General Recommendations Aerobic activity 150 min of moderate intensity or 75 min of vigorous intensity per week Resistance training Involving major muscle groups twice weekly Encourage enjoyable activities Walking, Zumba, Basketball, Kayaking Diabetes Care 2014;37(Suppl. 1):S14- S80 Physical Activity Patients with complications Peripheral neuropathy Stress foot care Foot injury or open sore restrict to non weight- bearing activities Autonomic neuropathy CV clearance warranted prior to beginning new activity Retinopathy Vigorous or resistance exercises may be contraindicated in proliferative or severe nonproliferative retinopathy Diabetes Care 2014;37(Suppl. 1):S14- S80 11

12 Physical Activity Elderly or patients with disabilities As tolerated Patients with nonoptimal glycemic control Hyperglycemia Avoid vigorous activity in ketosis Hypoglycemia Patients on insulin or secretagogues should eat carbs if glucose <100 mg/dl prior to exercise Diabetes Care 2014;37(Suppl. 1):S14- S80 Must be personal Reduced intake recommended for overweight/obese patients No ideal percent of calories from carbohydrates, protein, and fat Recommendations based on current eating patterns, preferences, metabolic goals Tradition Culture Religion Health beliefs and goals Economics Willingness to make changes Self monitoring of blood glucose readings can be used to adjust intake Diabetes Care 2014;37(Suppl. 1):S120 S143 12

13 Medical Nutrition Therapy Mediterranean Dietary Approaches to Stop Hypertension (DASH) Plant- based (vegan or vegetarian) Lower- fat Lower- carbohydrate Diabetes Care 2014;37(Suppl. 1):S120 S143 Most important factor influencing glycemic response after eating Evidence is inconclusive for an ideal amount of carbohydrate intake Encourage a variety of fiber- containing foods Vegetables, fruit, whole grains, legumes, and dairy products are preferred over other carbohydrate sources Especially those containing added fat, sugar, or sodium Sugar alcohols and nonnutritive sweeteners are considered safe Diabetes Care 2014;37(Suppl. 1):S120 S143 13

14 food- and- fitness/weight_management/tips_and_tools/rondinelli_jan06 food- and- fitness/weight_management/tips_and_tools/rondinelli_jan06 14

15 Biguanides me,ormin Sulfonylureas / Megli1nides glyburide glipizide glimepiride repaglinide nateglinide TZDs pioglitazone rosiglitazone α- Glucosidase inhibitors acarbose miglitol Ac1vates AMP- kinase Hepa1c glucose produc1on Closes KATP channels Insulin secre1on PPAR- γ ac1vator insulin sensi1vity Inhibits a- glucosidase Slows carbohydrate absorp1on Extensive experience No hypoglycemia Weight neutral? CVD Extensive experience Microvasc. risk No hypoglycemia Durability TGs, HDL- C? CVD (pio) No hypoglycemia Nonsystemic Post- prandial glucose? CVD events Table 1. Proper1es of an1- hyperglycemic agents Gastrointes1nal Lac1c acidosis B- 12 deficiency Contraindica1ons Hypoglycemia Weight gain Low durability? Ischemic precondi1oning Weight gain Edema / heart failure Bone fractures? MI (rosi)? Bladder ca (pio) Gastrointes1nal Dosing frequency Modest A1c Low Low High Moderate Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 15

16 DPP- 4 Inhibitors linaglip1n sitaglip1n GLP- 1 agonists exena1de liraglu1de albiglu1de Amylin mime1cs pramlin1de Bile acid sequestrants colesevelam Dopamine- 2 agonists bromocrip1ne Inhibits DPP- 4 Increases GLP- 1, GIP Ac1vates GLP- 1 R Insulin, glucagon gastric emptying sa1ety Ac1vates amylin receptor glucagon gastric emptying sa1ety Bind bile acids Hepa1c glucose produc1on Ac1vates DA receptor Modulates hypothalamic control of metabolism insulin sensi1vity No hypoglycemia Well tolerated Weight loss No hypoglycemia? Beta cell mass? CV protec1on Weight loss PPG No hypoglycemia Nonsystemic Post- prandial glucose CVD events No hypoglyemia? CVD events Table 1. Proper1es of an1- hyperglycemic agents Modest A1c? Pancrea11s Ur1caria GI? Pancrea11s Medullary ca (rats) Injectable GI Modest A1c Injectable Hypo w/ insulin Dosing frequency GI Modest A1c Dosing frequency Modest A1c Dizziness/syncope Nausea Fa1gue High High High High High Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] Insulin Ac1vates insulin receptor peripheral glucose uptake Universally effec1ve Unlimited efficacy Microvascular risk Hypoglycemia Weight gain? Mitogenicity Injectable Training requirements S1gma Variable Table 1. Proper1es of an1- hyperglycemic agents Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 16

17 SGLT- 2 Inhibitors Blocks transporter responsible for reabsorbing majority of glucose filtered by kidney Increases urinary glucose excretion Lowers blood glucose SGLT- 2 Inhibitors Canagliflozin, dapagliflozin, empagliflozin Efficacy Intermediate: 1% A1c reduction Diuresis Lowers BP Weight loss ADRs Mycotic urinary tract infections Females and uncircumcised males Typically not recurrent Urinary frequency, urgency Slight increase in LDL Low hypoglycemia risk High cost 17

18 Patient Centered Approach Metformin recommended first line in the absence of contraindications Additional agents selected based on 5 domains Efficacy Risk of hypoglycemia Affect on weight Major side effects Cost Other considerations Age Comorbidities Kidney, heart, liver disease ADA/EASD T2DM An1- hyperglycemic Therapy: General Recommenda1ons Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 18

19 ADA/EASD T2DM An1- hyperglycemic Therapy: General Recommenda1ons Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] ADA/EASD T2DM An1- hyperglycemic Therapy: General Recommenda1ons Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 19

20 ADA/EASD T2DM An1- hyperglycemic Therapy: General Recommenda1ons Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] Must be individualized based on Risk of hypoglycemia Affect on weight Ease of use Cost Comorbidities Kidney, heart, liver disease Recommendations stratified based on A1C 20

21 21

22 22

23 JL is a 42 y/o HM who was diagnosed with type 2 diabetes 8 months ago. He eats a typical Latin diet but exercises everyday by playing soccer and working out on weight bench in his garage. He does not have prescription insurance. He checks his glucose a few times a week and hates needles. PMH: T2DM, HTN Current meds: metformin 1000mg twice daily, lisinopril 10mg daily Labs: BP 128/76 P 78 Ht 5 5 Wt 171 BMI 28.5 Na 139 K 4.5 Cl 102 SCr 0.9 egfr >90 BUN 23 AST 17 ALT 19 Glu 233 A1C 7.8% What medication would you at to JL s current regimen? Adapted Recommenda1ons: When Goal is to Minimize Costs Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 23

24 Case 2, Continued SH reports that she has always struggled with her weight. She does not want to start a medication that will cause weight gain. In fact medications that assist with weight loss would be preferred. She does not care if it is oral or injectable and she has great insurance coverage. PMH: CAD, HTN, T2DM, sleep apnea, depression Current meds: metformin 500mg twice daily, atorvastatin 40mg daily, losartan 100mg daily, ranolazine 500mg twice daily, fluoxetine 20mg daily Labs: BP 132/78 P 73 Ht 5 3 Wt 240 BMI 42.5 Na 135 K 4.5 Cl 101 SCr 1.11 egfr 51 BUN 23 AST 17 ALT 19 Glu 233 A1c 8.5% What medication would add to SH s current regimen? Adapted Recommenda1ons: When Goal is to Avoid Weight Gain Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 24

25 1. Which of following drugs is classified as a sodium- glucose co- transporter - 2 (SLGT- 2) inhibitor? a. dapagliflozin b. glimepiride c. linagliptin d. metformin 25

26 Case: MJ is 44 y/o WF who presents for f/u. She reports she ran out of test strips about 3 months ago and didn t refill them because her sugars were always good. She also states she has been drinking a lot of sweet tea because the heat has made her REALLY thirsty and sleepy. PMH: Type 2 DM, HTN Current Medications: Lisinopril/hctz 20/25 daily, metformin 1000mg twice daily Allergies: KNDA Adherence: reports 100% O: BP 138/84, P 74, Ht 5 5, Wt 204, BMI 34, Glu 220, POC A1c 8.2% 2. True or False? MJ s diabetes is adequately controlled on her current regimen. 26

27 3. What A1c goal would you recommend for MJ? a. <6.0 b. <6.5% c. <7.0% d. <8.0% 4. What therapeutic agent would you add to MJ s diabetes regimen at this time? a. glipizide b. liraglutide c. pioglitazone d. saxagliptin 27

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