Transcript grand rounds_jfma_sept 2010[1]

Getting to Goal:
Strategies for Diabetes
Management
Amy M. Egras, Pharm.D., BCPS
JFMA Grand Rounds
September 1, 2010
Objectives
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Discuss strategies to get patients with
diabetes to their A1c goal.
Discuss strategies to get patients with
diabetes to their BP goal.
Discuss strategies to get patients with
diabetes to their LDL goal.
Diabetes Goals
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HgA1c < 7%
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BP goal of < 130/80 mmHg
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63% of patients are NOT at goal
64.2% of patients are NOT at goal
LDL goal of < 100 mg/dL
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48.2% of patients are NOT at their cholesterol goal of
< 200 mg/dL
HMO data: 71.2% of DM patients NOT at LDL goal
FHS data:
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50 yo: 76.9% of patients NOT at LDL goal
60 yo: 60% of patients NOT at LDL goal
JAMA. 2004;291:335-342.
J Manag Care Pharm. 2007;13:652-663.
Circulation. 2009;120:212-220.
Cardiovascular Risks
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↑ 2-3 fold risk for CVD
Heart disease & stroke rates are 2-4 times
higher
68% of diabetes-related deaths due to heart
disease
 16% of diabetes-related deaths due to stroke

Circulation. 2009;120:212-220.
www.cdc.gov/diabetes/pubs/estimates07.htm
Goals & Prevention of CVD
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Glycemic control
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Blood pressure control
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Long term follow-up suggests long-term
reduction in macrovascular complications
Reduces risk of CVD by 33-50%
LDL cholesterol control
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Reduce CVD complications 20-50%
Diabetes Care. 2009;32:187-192.
www.cdc.gov/diabetes/pubs/estimates07.htm
Glycemic Control
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Therapeutic Options
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Metformin
Sulfonylureas
TZDs
Insulin
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DPP-4 inhibitors
Glinides
α-glucosidase
inhibitors
Incretin mimetics
Dipeptidyl Peptidase-4 Inhibitors
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Agents & dosing
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Place in therapy
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Sitagliptin (Januvia®) 100 mg po daily
Saxagliptin (Onglyza®) 2.5 – 5 mg po daily
Add on therapy for type 2 diabetes patients
↓ A1C 0.7-1%
Adverse effects: GI upset, headache, URI,
peripheral edema (more common with
saxagliptin), hypoglycemia (more common with
saxagliptin and insulin secretagogues)
Glinides:
Short-Acting Insulin Secretagogues
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Agents & dosing
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Nateglinide (Starlix®) 60-120 mg with each meal
Repaglinide (Prandin®) 0.5-2 mg with each meal
Place in therapy:
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Add on therapy for postprandial glucose control
↓ A1C 0.5-1%
Glinides:
Short-Acting Insulin Secretagogues
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Adverse effects: Hypoglycemia, weight gain
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Comments
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Can be used in patients with renal insufficiency
Rapidly absorbed with a short duration of action
If a meal is skipped, the medication should NOT be
taken
Do NOT use in combination with a sulfonylureas
Alpha-glucosidase Inhibitors
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Agents & dosing
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Place in therapy:
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Acarbose (Precose®) 25-100 mg po TID with first bite of each
meal
Miglitol (Glyset®) 25-200 mg po TID with first bite of each meal
Add on therapy for postprandial glucose control
↓ A1C 0.5-1%
Adverse effects: Hypoglycemia, flatulence, abdominal
discomfort, bloating, diarrhea, ↑ LFTs (rarely)
Alpha-glucosidase Inhibitors
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Contraindicated in:
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Short bowel syndrome
Inflammatory bowel disease
Renal impairment (SCr > 2.0)
Comments
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Hypoglycemia must be treated with GLUCOSE, not
sucrose
If a meal is skipped, the medication should be
skipped as well
Incretin Mimetics
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Agent & dosing
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Exenatide (Byetta®) 5-10 mcg SQ BID
Liraglutide (Victoza®) 1.2-1.8 mg SQ daily
Place in therapy
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Patients who are taking:
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Sulfonylurea
Metformin
Combination of sulfonylurea & metformin
↓ A1C 0.5-1%
Incretin Mimetics
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Adverse effects: Nausea, vomiting,
diarrhea, dyspepsia, hypoglycemia, weight
loss, acute pancreatitis
Precautions
Gastroparesis
 ESRD or ClCr < 30 mL/min (exenatide only)
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Incretin Mimetics
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Comments
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Administer within 0-60 minutes before the morning
and evening meals (exenatide)
Dose may be titrated
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Exenatide: increase to 10 mcg BID after one month of
therapy
Liraglutide: start with 0.6 mg for 1 week, then increase to 1.2
mg daily; if glycemic response is not optimal, may increase
to 1.8 mg daily
May need to decrease dose of insulin secretagogue
to reduce the risk of hypoglycemia
Incretin Mimetics
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Comments
Store in refrigerator
 Available in prefilled syringes
 Patient education for pen use and medication
administration
 Pen needles are NOT included
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Achieving BP Goal
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Blood Pressure Goals
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Most patients will likely need at least 3
medications to get their BP to goal
2005-2006 NHANES found 64% of
patients with treated HTN achieved their
BP goal
NCHS Data Brief. 2008 Jan;(3):1-8.
Pharmacological Treatment
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Initial therapy should include:
ACE-inhibitor, OR
 ARB
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If still not at goal, add a thiazide diuretic
CrCl > 30 mL/min
 Synergy with ACE-I or ARB
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Monitor: potassium, kidney function
Diabetes Care. 2010;33:Supplement 1.
Other Agents
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ß-blockers
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Benefit in those with CAD or HF
Monitor heart rate
Calcium channel blockers
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Non-dihydropyridines (verapamil, diltiazem)
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Kidney protective effects
Caution: use with ß-blockers, monitor heart rate,
constipation
Dihydropyridines (amlodipine, nifedipine, felodipine)
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ACCOMPLISH trial showed decrease in CV events
Caution: peripheral edema
Other Agents
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Clonidine
Anticholinergic side effects
 Rebound HTN with abrupt withdrawal
 Use extreme caution with ß-blockers!!
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Aldosterone antagonists (spironolactone)
Beware of hyperkalemia especially if used
with an ACE-I or ARB
 Gynecomastia; do not use in CrCl < 30
mL/min or SCr > 2.5 mg/dL
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Resistant Hypertension
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Definition: BP remains above goal with
the concurrent use of 3 antihypertensive
medications of different classes
Medications at optimal doses
 1 medication is a diuretic
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Consider an evaluation for secondary
hypertension
Remember…
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Lifestyle modifications
Reduce sodium intake
 Weight loss
 Increase fruits, vegetables, and low-fat dairy
 Avoid excessive alcohol consumption
 Increase physical activity
 Smoking cessation
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Combination products
Achieving LDL Goal
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Statins
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Pts with CVD or > 40 yo with CVD risk factors should be
started on a statin that lowers LDL 30-40% regardless of
baseline LDL
Statin
Dose
(mg/day)
LDL-C reduction (%)
Atorvastatin
10
39
Fluvastatin
80
35
Lovastatin
40
31
Pravastatin
40
34
Rosuvastatin
5-10
39-45
Simvastatin
20-40
35-41
Diabetes Care. 2010;33:Supplement 1.
Determine % LDL Reduction
% reduction in LDL needed = (Current LDL- LDL goal) X 100
Current LDL
% reduction in LDL needed = (191- 100) X 100
191
Patient needs a 48% decrease in LDL
Potency of Statins
Statin Approximate
Equivalent Dose
Percent Change from
Baseline LDL
Initial dosing
Atorvastatin 10 mg
Lovastatin 40 mg
Pravastatin 40 mg
Simvastatin 20 mg
-31 to -38%
For a 30-40% reduction in LDL-C
Atorvastatin 20 mg
Lovastatin 80 mg
Rosuvastatin 5 mg
Simvastatin 40 mg
-45 to -48%
For a 45-50% reduction in LDL-C
Atorvastatin 40 mg
Rosuvastatin 10 mg
Simvastatin 80 mg
-46 to -48%
For a 50% reduction in LDL-C
Atorvastatin 80 mg
Rosuvastatin 20 mg
-51 to -52%
For > 50% reduction in LDL-C
(but will likely need to add
additional therapy)
NOTE: Ratio of simvastatin to atorvastatin is 2:1; ratio of atorvastatin to rosuvastatin is 4:1;
ratio of simvastatin to rosuvastatin is 8:1
Am J Cardiol. 1998;81(5):582-7.
Am J Cardiol. 2003;92(2):152-60.
Adjusting Doses
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Recheck FLP in 6 weeks
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Not at goal?
Double the dose: produces an additional 6%
↓ in LDL from baseline or an additional 10
mg/dL LDL drop
 Switch to a more potent statin
 Add another agent
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Other Agents to Consider
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Bile acid sequestrants
Ezetimibe
Fibrate
Niacin
Statin + BAS
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Products
Cholestyramine (Questran®)
 Colestipol (Colestid®)
 Colesevelam (WelChol®)
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Studies have shown an additional 7-20%
reduction in LDL
J Fam Pract. 2006;55:70-2.
Statin + BAS
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For BAS:
Contraindications: GI obstruction, dysphagia,
TG > 300 mg/dL
 SEs: Constipation, GI upset
 Drug interactions
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Can directly bind other drugs and ↓ absorption
 Should be administered 1 hour before or 4-6 hours
after other drugs
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Start low and go slow!
Statin + Ezetimibe
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Zetia®
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Additional 12-21% decrease in LDL
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Clinical pearls
Very well tolerated
 Increase in hepatic transaminases
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J Fam Pract. 2006;55:70-2.
Statin + Fibrate
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Products
Gemfibrozil (Lopid®)
 Fenofibrate (Tricor®, Triglide®, Lofibra®,
Antara®)
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Results in:
40% decrease in LDL
 > 50% decrease in triglycerides
 20% increase in HDL
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J Fam Pract. 2006;55:70-2.
Statin + Fibrate
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Increased risk of myopathy in combination
(greater with gemfibrozil)
For fibrates:
Contraindications: Active liver disease,
gallbladder disease, CrCl < 30 mL/min
 SEs: GI upset, cholelithiasis, hepatotoxicity
(rare), ↑ CPK
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Statin + Niacin
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Products
Immediate release (IR)
 Sustained release (Slo-Niacin®, Nicobid®)
 Extended release (Niaspan®)
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Results in:
> 40% decrease in LDL
 > 40% decrease in triglycerides
 > 30% increase in HDL
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Clin Cardiol. 2003;26:112-8.
Arch Intern Med. 2004;64:1121-7.
Statin + Niacin
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Increased risk of myopathy in combination
For niacin:
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Contraindications: Active liver disease, active peptic
ulcer disease, active gout
Caution: poorly controlled diabetes
SEs: GI upset, flushing, itching, hepatotoxicity
(highest with sustained release)
Dosing considerations
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Take aspirin 325 mg before each dose
Take with food
Start low and titrate up the dose slowly
Avoid dosing with warm beverages
Combination Products
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Ezetimibe with simvastatin (Vytorin®)
Extended-release niacin with simvastatin
(Simcor®)
Extended-release niacin with lovastatin
(Advicor®)
Atorvastatin with amlodipine (Caduet®)
Remember…
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Lifestyle modifications
Decrease saturated fat, trans fat, and
cholesterol
 Increase omega-3-fatty acids, viscous fiber,
and plant stanols/sterols
 Weight loss
 Increase physical activity
 Smoking cessation
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Back to Basics
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