Type 2 Diabetes It's Personal - c.ymcdn.com · 9/29/14 3 •...

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Disclosures • Nothing to disclose

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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

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• 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

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Estimates of Diagnosed Diabetes among Adults aged ≥ 20 years

http://www.cdc.gov/diabetes/surveillance/diabetes_slides.htm

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• Diagnose and assess control of diabetes • Percent hemoglobin in red blood cells that is glycated •  Estimate of average glucose over previous 2-‐3 months

http://professional.diabetes.org/GlucoseCalculator.aspx

ADA AACE

A1C <7.0% ≤ 6.5%

Preprandial glucose 70-‐130 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): 1-‐53.

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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


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Glucose Goals in Elderly


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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

https://www.dtu.ox.ac.uk/ukpds_trial/index.php

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;359:1577-‐89

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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:

What A1C goal would you recommend for JL?

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%

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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:

What A1C goal would you recommend for SH?

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%

Lifestyle Modifications

Weight loss

Tobacco cessation

Moderation of alcohol

Physical activity

Medical nutrition therapy


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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


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


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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


• 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

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Medical Nutrition Therapy

Mediterranean

Dietary Approaches to

Stop Hypertension (DASH)

Plant-‐based (vegan or vegetarian)

Lower-‐fat Lower-‐carbohydrate


• 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


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http://www.dlife.com/diabetes-‐food-‐and-‐fitness/weight_management/tips_and_tools/rondinelli_jan06

http://www.dlife.com/diabetes-‐food-‐and-‐fitness/weight_management/tips_and_tools/rondinelli_jan06

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Biguanides •  me,ormin

•  Ac1vates AMP-‐kinase •  Hepa1c glucose produc1on

•  Extensive experience •  No hypoglycemia •  Weight neutral •  ? CVD

•  Gastrointes1nal •  Lac1c acidosis •  B-‐12 deficiency •  Contraindica1ons

Low

Sulfonylureas / Megli1nides •  glyburide •  glipizide •  glimepiride •  repaglinide •  nateglinide

•  Closes KATP channels •  Insulin secre1on

•  Extensive experience •  Microvasc. risk

•  Hypoglycemia •  Weight gain •  Low durability •  ? Ischemic precondi1oning

Low

TZDs •  pioglitazone •  rosiglitazone

•  PPAR-‐γ ac1vator •  insulin sensi1vity

•  No hypoglycemia •  Durability •  TGs, HDL-‐C •  ? CVD (pio)

•  Weight gain •  Edema / heart failure •  Bone fractures •  ? MI (rosi) •  ? Bladder ca (pio)

High

α-‐Glucosidase inhibitors •  acarbose •  miglitol

•  Inhibits a-‐glucosidase •  Slows carbohydrate absorp1on

•  No hypoglycemia •  Nonsystemic •  Post-‐prandial glucose •  ? CVD events

•  Gastrointes1nal •  Dosing frequency •  Modest A1c

Moderate

Table 1. Proper1es of an1-‐hyperglycemic agents Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

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DPP-‐4 Inhibitors • linaglip1n • sitaglip1n

•  Inhibits DPP-‐4 •  Increases GLP-‐1, GIP

•  No hypoglycemia •  Well tolerated

•  Modest A1c •  ? Pancrea11s •  Ur1caria

High

GLP-‐1 agonists • exena1de • liraglu1de •  albiglu1de

•  Ac1vates GLP-‐1 R •  Insulin, glucagon •  gastric emptying •  sa1ety

•  Weight loss •  No hypoglycemia •  ? Beta cell mass •  ? CV protec1on

•  GI •  ? Pancrea11s •  Medullary ca (rats) •  Injectable

High

Amylin mime1cs • pramlin1de

•  Ac1vates amylin receptor •  glucagon •  gastric emptying •  sa1ety

•  Weight loss •  PPG

•  GI •  Modest A1c •  Injectable •  Hypo w/ insulin •  Dosing frequency

High

Bile acid sequestrants • colesevelam

•  Bind bile acids •  Hepa1c glucose produc1on

•  No hypoglycemia •  Nonsystemic •  Post-‐prandial glucose •  CVD events

•  GI •  Modest A1c •  Dosing frequency

High

Dopamine-‐2 agonists • bromocrip1ne

•  Ac1vates DA receptor •  Modulates hypothalamic control of metabolism •  insulin sensi1vity

•  No hypoglyemia •  ? CVD events

•  Modest A1c •  Dizziness/syncope •  Nausea •  Fa1gue

High


Insulin •  Ac1vates insulin receptor •  peripheral glucose uptake

•  Universally effec1ve •  Unlimited efficacy •  Microvascular risk

•  Hypoglycemia •  Weight gain •  ? Mitogenicity •  Injectable •  Training requirements •  “S1gma”

Variable


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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

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• 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]

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


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• 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

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https://www.aace.com

/publications/algorithm

https://www.aace.com

/publications/algorithm

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http://diabetesdecisionaid.mayoclinic.org/

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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:

What medication would you at to JL’s current regimen?

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%

Adapted Recommenda1ons: When Goal is to Minimize Costs Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

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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:

What medication would add to SH’s current regimen?

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%

Adapted Recommenda1ons: When Goal is to Avoid Weight Gain Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

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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

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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.

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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

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