Getting to Goal:  Getting to Goal:  Strategies for Strategies for

Diabetes ManagementDiabetes Management

Amy M. Egras, Pharm.D., Amy M. Egras, Pharm.D., BCPSBCPS

JFMA Grand RoundsJFMA Grand Rounds

September 1, 2010September 1, 2010

ObjectivesObjectives

Discuss strategies to get patients Discuss strategies to get patients with diabetes to their A1c goal.with diabetes to their A1c goal.

Discuss strategies to get patients Discuss strategies to get patients with diabetes to their BP goal.with diabetes to their BP goal.

Discuss strategies to get patients Discuss strategies to get patients with diabetes to their LDL goal.with diabetes to their LDL goal.

Diabetes GoalsDiabetes Goals HgA1c < 7%HgA1c < 7%

63% of patients are NOT at goal63% of patients are NOT at goal BP goal of < 130/80 mmHgBP goal of < 130/80 mmHg

64.2% of patients are NOT at goal64.2% of patients are NOT at goal LDL goal of < 100 mg/dLLDL goal of < 100 mg/dL

48.2% of patients are NOT at their cholesterol 48.2% of patients are NOT at their cholesterol goal of < 200 mg/dLgoal of < 200 mg/dL

HMO data: 71.2% of DM patients NOT at LDL HMO data: 71.2% of DM patients NOT at LDL goalgoal

FHS data:FHS data: 50 yo: 76.9% of patients NOT at LDL goal50 yo: 76.9% of patients NOT at LDL goal 60 yo: 60% of patients NOT at LDL goal60 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 RisksCardiovascular Risks

↑ ↑ 2-3 fold risk for CVD2-3 fold risk for CVD Heart disease & stroke rates are 2-4 Heart disease & stroke rates are 2-4

times highertimes higher 68% of diabetes-related deaths due to 68% of diabetes-related deaths due to

heart diseaseheart disease 16% of diabetes-related deaths due to 16% of diabetes-related deaths due to

strokestroke

Circulation. 2009;120:212-220.www.cdc.gov/diabetes/pubs/estimates07.htm

Goals & Prevention of Goals & Prevention of CVDCVD

Glycemic controlGlycemic control Long term follow-up suggests long-term Long term follow-up suggests long-term

reduction in macrovascular reduction in macrovascular complicationscomplications

Blood pressure controlBlood pressure control Reduces risk of CVD by 33-50%Reduces risk of CVD by 33-50%

LDL cholesterol controlLDL cholesterol control Reduce CVD complications 20-50%Reduce CVD complications 20-50%

Diabetes Care. 2009;32:187-192.www.cdc.gov/diabetes/pubs/estimates07.htm

Glycemic ControlGlycemic Control

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Therapeutic OptionsTherapeutic Options

MetforminMetformin SulfonylureasSulfonylureas TZDsTZDs InsulinInsulin

DPP-4 inhibitorsDPP-4 inhibitors GlinidesGlinides αα--glucosidase glucosidase

inhibitorsinhibitors Incretin mimeticsIncretin mimetics

Dipeptidyl Peptidase-4 Dipeptidyl Peptidase-4 InhibitorsInhibitors

Agents & dosingAgents & dosing Sitagliptin (JanuviaSitagliptin (Januvia®®) 100 mg po daily) 100 mg po daily Saxagliptin (OnglyzaSaxagliptin (Onglyza®®) 2.5 – 5 mg po daily) 2.5 – 5 mg po daily

Place in therapyPlace in therapy Add on therapy for type 2 diabetes patientsAdd on therapy for type 2 diabetes patients ↓ ↓ A1C 0.7-1%A1C 0.7-1%

Adverse effects: GI upset, headache, URI, Adverse effects: GI upset, headache, URI, peripheral edema (more common with peripheral edema (more common with saxagliptin), hypoglycemia (more common saxagliptin), hypoglycemia (more common with saxagliptin and insulin secretagogues)with saxagliptin and insulin secretagogues)

Glinides:Glinides:Short-Acting Insulin Short-Acting Insulin

SecretagoguesSecretagogues Agents & dosingAgents & dosing

Nateglinide (StarlixNateglinide (Starlix®®) 60-120 mg with each ) 60-120 mg with each mealmeal

Repaglinide (PrandinRepaglinide (Prandin®®) 0.5-2 mg with each ) 0.5-2 mg with each mealmeal

Place in therapy: Place in therapy: Add on therapy for postprandial glucose controlAdd on therapy for postprandial glucose control ↓ ↓ A1C 0.5-1%A1C 0.5-1%

Glinides:Glinides:Short-Acting Insulin Short-Acting Insulin

SecretagoguesSecretagogues Adverse effects: Hypoglycemia, weight gainAdverse effects: Hypoglycemia, weight gain

CommentsComments Can be used in patients with renal insufficiencyCan be used in patients with renal insufficiency Rapidly absorbed with a short duration of actionRapidly absorbed with a short duration of action If a meal is skipped, the medication should NOT If a meal is skipped, the medication should NOT

be takenbe taken Do Do NOTNOT use in combination with a sulfonylureas use in combination with a sulfonylureas

Alpha-glucosidaseAlpha-glucosidase InhibitorsInhibitors

Agents & dosingAgents & dosing Acarbose (PrecoseAcarbose (Precose®®) 25-100 mg po TID with first bite of ) 25-100 mg po TID with first bite of

each mealeach meal Miglitol (GlysetMiglitol (Glyset®®) 25-200 mg po TID with first bite of ) 25-200 mg po TID with first bite of

each mealeach meal

Place in therapy:Place in therapy: Add on therapy for postprandial glucose controlAdd on therapy for postprandial glucose control ↓ ↓ A1C 0.5-1%A1C 0.5-1%

Adverse effects: Hypoglycemia, flatulence, Adverse effects: Hypoglycemia, flatulence, abdominal discomfort, bloating, diarrhea, abdominal discomfort, bloating, diarrhea, ↑ ↑ LFTs LFTs (rarely)(rarely)

Alpha-glucosidase Alpha-glucosidase InhibitorsInhibitors

Contraindicated in:Contraindicated in: Short bowel syndromeShort bowel syndrome Inflammatory bowel diseaseInflammatory bowel disease Renal impairment (SCr > 2.0)Renal impairment (SCr > 2.0)

CommentsComments Hypoglycemia must be treated with GLUCOSE, Hypoglycemia must be treated with GLUCOSE,

not sucrosenot sucrose If a meal is skipped, the medication should be If a meal is skipped, the medication should be

skipped as wellskipped as well

Incretin MimeticsIncretin Mimetics

Agent & dosingAgent & dosing Exenatide (ByettaExenatide (Byetta®®) 5-10 mcg SQ BID) 5-10 mcg SQ BID Liraglutide (Victoza®) 1.2-1.8 mg SQ dailyLiraglutide (Victoza®) 1.2-1.8 mg SQ daily

Place in therapyPlace in therapy Patients who are taking:Patients who are taking:

SulfonylureaSulfonylurea MetforminMetformin Combination of sulfonylurea & metforminCombination of sulfonylurea & metformin

↓ ↓ A1C 0.5-1%A1C 0.5-1%

Incretin MimeticsIncretin Mimetics

Adverse effects: Nausea, vomiting, Adverse effects: Nausea, vomiting, diarrhea, dyspepsia, hypoglycemia, diarrhea, dyspepsia, hypoglycemia, weight loss, acute pancreatitisweight loss, acute pancreatitis

PrecautionsPrecautions GastroparesisGastroparesis ESRD or ClCr < 30 mL/min (exenatide ESRD or ClCr < 30 mL/min (exenatide

only)only)

Incretin MimeticsIncretin Mimetics

CommentsComments Administer within 0-60 minutes before the Administer within 0-60 minutes before the

morning and evening meals (exenatide)morning and evening meals (exenatide) Dose may be titratedDose may be titrated

Exenatide: increase to 10 mcg BID after one month Exenatide: increase to 10 mcg BID after one month of therapyof therapy

Liraglutide: start with 0.6 mg for 1 week, then Liraglutide: start with 0.6 mg for 1 week, then increase to 1.2 mg daily; if glycemic response is not increase to 1.2 mg daily; if glycemic response is not optimal, may increase to 1.8 mg dailyoptimal, may increase to 1.8 mg daily

May need to decrease dose of insulin May need to decrease dose of insulin secretagogue to reduce the risk of secretagogue to reduce the risk of hypoglycemiahypoglycemia

Incretin MimeticsIncretin Mimetics

CommentsComments Store in refrigeratorStore in refrigerator Available in prefilled syringesAvailable in prefilled syringes Patient education for pen use and Patient education for pen use and

medication administrationmedication administration Pen needles are NOT includedPen needles are NOT included

Achieving BP Achieving BP GoalGoal

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Blood Pressure GoalsBlood Pressure Goals

Most patients will likely need at least Most patients will likely need at least 3 medications to get their BP to goal3 medications to get their BP to goal

2005-2006 NHANES found 64% of 2005-2006 NHANES found 64% of patients with treated HTN achieved patients with treated HTN achieved their BP goaltheir BP goal

NCHS Data Brief. 2008 Jan;(3):1-8.

Pharmacological Pharmacological TreatmentTreatment

Initial therapy should include:Initial therapy should include: ACE-inhibitor, ACE-inhibitor, OROR ARBARB

If still not at goal, add a thiazide If still not at goal, add a thiazide diureticdiuretic CrCl > 30 mL/minCrCl > 30 mL/min Synergy with ACE-I or ARBSynergy with ACE-I or ARB

Monitor: potassium, kidney functionMonitor: potassium, kidney function

Diabetes Care. 2010;33:Supplement 1.

Other AgentsOther Agents ß-blockersß-blockers

Benefit in those with CAD or HFBenefit in those with CAD or HF Monitor heart rateMonitor heart rate

Calcium channel blockersCalcium channel blockers Non-dihydropyridines (verapamil, diltiazem)Non-dihydropyridines (verapamil, diltiazem)

Kidney protective effectsKidney protective effects Caution: use with ß-blockers, monitor heart rate, Caution: use with ß-blockers, monitor heart rate,

constipationconstipation Dihydropyridines (amlodipine, nifedipine, Dihydropyridines (amlodipine, nifedipine,

felodipine)felodipine) ACCOMPLISH trial showed decrease in CV eventsACCOMPLISH trial showed decrease in CV events Caution: peripheral edemaCaution: peripheral edema

Other AgentsOther Agents

ClonidineClonidine Anticholinergic side effectsAnticholinergic side effects Rebound HTN with abrupt withdrawalRebound HTN with abrupt withdrawal Use extreme caution with ß-blockers!!Use extreme caution with ß-blockers!!

Aldosterone antagonists Aldosterone antagonists (spironolactone)(spironolactone) Beware of hyperkalemia especially if Beware of hyperkalemia especially if

used with an ACE-I or ARBused with an ACE-I or ARB Gynecomastia; do not use in CrCl < 30 Gynecomastia; do not use in CrCl < 30

mL/min or SCr > 2.5 mg/dLmL/min or SCr > 2.5 mg/dL

Resistant HypertensionResistant Hypertension

Definition: BP remains above goal Definition: BP remains above goal with the concurrent use of 3 with the concurrent use of 3 antihypertensive medications of antihypertensive medications of different classesdifferent classes Medications at optimal dosesMedications at optimal doses 1 medication is a diuretic1 medication is a diuretic

Consider an evaluation for secondary Consider an evaluation for secondary hypertensionhypertension

Remember…Remember…

Lifestyle modificationsLifestyle modifications Reduce sodium intakeReduce sodium intake Weight lossWeight loss Increase fruits, vegetables, and low-fat Increase fruits, vegetables, and low-fat

dairydairy Avoid excessive alcohol consumptionAvoid excessive alcohol consumption Increase physical activityIncrease physical activity Smoking cessationSmoking cessation

Combination productsCombination products

Achieving LDL Achieving LDL GoalGoal

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StatinsStatins Pts with CVD or > 40 yo with CVD risk factors Pts with CVD or > 40 yo with CVD risk factors

should be started on a statin that lowers LDL 30-should be started on a statin that lowers LDL 30-40% regardless of baseline LDL40% 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 Determine % LDL ReductionReduction

% reduction in LDL needed = (Current LDL- LDL goal)X 100

Current LDL

Patient needs a 48% decrease in LDL

% reduction in LDL needed = (191- 100) X 100 191

Potency of StatinsPotency of StatinsStatin

Approximate Equivalent

Dose

Percent Change from Baseline LDL

Initial dosing

Atorvastatin 10 mgLovastatin 40 mgPravastatin 40 mgSimvastatin 20 mg

-31 to -38% For a 30-40% reduction in LDL-C

Atorvastatin 20 mgLovastatin 80 mgRosuvastatin 5 mgSimvastatin 40 mg

-45 to -48% For a 45-50% reduction in LDL-C

Atorvastatin 40 mgRosuvastatin 10 mgSimvastatin 80 mg

-46 to -48% For a 50% reduction in LDL-C

Atorvastatin 80 mgRosuvastatin 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 DosesAdjusting Doses

Recheck FLP in 6 weeksRecheck FLP in 6 weeks

Not at goal?Not at goal? Double the dose: produces an Double the dose: produces an

additional 6% ↓ in LDL from baseline or additional 6% ↓ in LDL from baseline or an additional 10 mg/dL LDL dropan additional 10 mg/dL LDL drop

Switch to a more potent statinSwitch to a more potent statin Add another agentAdd another agent

Other Agents to ConsiderOther Agents to Consider

Bile acid sequestrantsBile acid sequestrants EzetimibeEzetimibe FibrateFibrate NiacinNiacin

Statin + BASStatin + BAS

ProductsProducts Cholestyramine (QuestranCholestyramine (Questran®)) Colestipol (ColestidColestipol (Colestid®)) Colesevelam (WelCholColesevelam (WelChol®))

Studies have shown an additional 7-Studies have shown an additional 7-20% reduction in LDL20% reduction in LDL

J Fam Pract. 2006;55:70-2.

Statin + BASStatin + BAS

For BAS:For BAS: Contraindications: GI obstruction, Contraindications: GI obstruction,

dysphagia, TG > 300 mg/dLdysphagia, TG > 300 mg/dL SEs: Constipation, GI upsetSEs: Constipation, GI upset Drug interactions Drug interactions

Can directly bind other drugs and ↓ Can directly bind other drugs and ↓ absorptionabsorption

Should be administered 1 hour before or 4-6 Should be administered 1 hour before or 4-6 hours after other drugshours after other drugs

Start low and go slow!Start low and go slow!

Statin + EzetimibeStatin + Ezetimibe

ZetiaZetia®

Additional 12-21% decrease in LDLAdditional 12-21% decrease in LDL

Clinical pearlsClinical pearls Very well toleratedVery well tolerated Increase in hepatic transaminasesIncrease in hepatic transaminases

J Fam Pract. 2006;55:70-2.

Statin + FibrateStatin + Fibrate

ProductsProducts Gemfibrozil (LopidGemfibrozil (Lopid®)) Fenofibrate (TricorFenofibrate (Tricor®, Triglide, Triglide®, Lofibra, Lofibra®, ,

AntaraAntara®))

Results in:Results in: 40% decrease in LDL40% decrease in LDL > 50% decrease in triglycerides> 50% decrease in triglycerides 20% increase in HDL20% increase in HDL

J Fam Pract. 2006;55:70-2.

Statin + FibrateStatin + Fibrate

Increased risk of myopathy in Increased risk of myopathy in combination (greater with combination (greater with gemfibrozil)gemfibrozil)

For fibrates:For fibrates: Contraindications: Active liver disease, Contraindications: Active liver disease,

gallbladder disease, CrCl < 30 mL/mingallbladder disease, CrCl < 30 mL/min SEs: GI upset, cholelithiasis, SEs: GI upset, cholelithiasis,

hepatotoxicity (rare), hepatotoxicity (rare), ↑ ↑ CPKCPK

Statin + NiacinStatin + Niacin

ProductsProducts Immediate release (IR)Immediate release (IR) Sustained release (Slo-NiacinSustained release (Slo-Niacin®, Nicobid, Nicobid®)) Extended release (NiaspanExtended release (Niaspan®))

Results in:Results in: > 40% decrease in LDL> 40% decrease in LDL > 40% decrease in triglycerides> 40% decrease in triglycerides > 30% increase in HDL> 30% increase in HDL

Clin Cardiol. 2003;26:112-8.Arch Intern Med. 2004;64:1121-7.

Statin + NiacinStatin + Niacin Increased risk of myopathy in combinationIncreased risk of myopathy in combination For niacin:For niacin:

Contraindications: Active liver disease, active Contraindications: Active liver disease, active peptic ulcer disease, active goutpeptic ulcer disease, active gout

Caution: poorly controlled diabetesCaution: poorly controlled diabetes SEs: GI upset, flushing, itching, hepatotoxicity SEs: GI upset, flushing, itching, hepatotoxicity

(highest with sustained release)(highest with sustained release) Dosing considerationsDosing considerations

Take aspirin 325 mg before each doseTake aspirin 325 mg before each dose Take with foodTake with food Start low and titrate up the dose slowlyStart low and titrate up the dose slowly Avoid dosing with warm beveragesAvoid dosing with warm beverages

Combination ProductsCombination Products

Ezetimibe with simvastatin (VytorinEzetimibe with simvastatin (Vytorin®®))

Extended-release niacin with simvastatin Extended-release niacin with simvastatin (Simcor(Simcor®®))

Extended-release niacin with lovastatin Extended-release niacin with lovastatin (Advicor(Advicor®®))

Atorvastatin with amlodipine (CaduetAtorvastatin with amlodipine (Caduet®®))

Remember…Remember…

Lifestyle modificationsLifestyle modifications Decrease saturated fat, Decrease saturated fat, transtrans fat, and fat, and

cholesterolcholesterol Increase omega-3-fatty acids, viscous Increase omega-3-fatty acids, viscous

fiber, and plant stanols/sterolsfiber, and plant stanols/sterols Weight lossWeight loss Increase physical activityIncrease physical activity Smoking cessationSmoking cessation

Back to BasicsBack to Basics

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