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Metabolic

Syndrome

Emily Clemens, PharmD


PGY1 Pharmacy Resident
Richard L. Roudebush VA Medical Center
Emily.Clemens@va.gov
About Me
Objectives
• Define the components of metabolic syndrome
• Understand the diagnostic criteria for metabolic
syndrome
• Calculate body mass index (BMI) and explain the
BMI classifications
• Evaluate treatment options including non-
pharmacologic options
• Determine when a patient would be a good
candidate for medication therapy
• Cite clinical pearls of medications and determine
the best option of treatment based on patient
specific factors
When you think
metabolic
syndrome…
Metabolic Syndrome

Abnormalities of metabolic origin


associated with the increased risk
of developing atherosclerotic
cardiovascular disease (ASCVD)
and Type 2 Diabetes

Grundy SM, Cleeman JI, Daniels SR, et al. Circulation. 2005;112:2735-2752.


Ruderman N, Shulman G. J Clin Endocrinol Metab 2016:43:752-769.
Three C’s of Metabolic Syndrome

Components •T2DM
•CVD
• Abdominal •Hyperuricemia
obesity •PCOS
• Abdominal obesity
• Inactivity • Insulin resistance •OSA
• Ethnicity •Fatty liver disease
• Elevated triglycerides
• Age
• Low HDL
• Gender • High blood pressure

Causes Consequences
T2DM=Type 2 Diabetes; CVD=Cardiovascular disease,
PCOS= Polycystic Ovary Syndrome , OSA=obstructive sleep apnea
Diagnostic Criteria: Pick 3

BP ≥ 130/85 mmHg OR drug therapy for hypertension

Fasting glucose ≥100 mg/dL OR drug therapy for elevated blood glucose

Triglycerides ≥ 150 mg/dL OR drug therapy for elevated triglycerides

HDL≤ 40 mg/dL for men or ≤ 50 mg/dL for women

Waist circumference ≥ 40 in for men and ≥ 35 in for women


Patient Case
AC is a 58 YOWM with PMH of HTN and T2DM

• Ht: 6’2” • Labs:


• Wt: 285 lbs • CrCl: 28 mL/min
• Fasting BG: 190 mg/dL
• Waist circumference: 41’’
• Lipids
• Vitals: • TC: 160 mg/dL
• HR: 75 bpm • TG: 131 mg/dL
• BP: 128/76 mmHg • HDL: 48 mg/dL
• Medications: • LDL: 101 mg/dL
• Losartan 100 mg PO daily
• Metformin 1000mg PO BID

Does AC have metabolic syndrome? If so, what criteria does he meet?


Diagnostic Criteria: Pick 3

BP ≥ 130/85 mmHg OR drug therapy for hypertension

Fasting glucose ≥100 mg/dL OR drug therapy for elevated blood glucose

Triglycerides ≥ 150 mg/dL OR drug therapy for elevated triglycerides

HDL≤ 40 mg/dL for men or ≤ 50 mg/dL for women

Waist circumference ≥ 40 in for men and ≥ 35 in for women


Management

Managing
Lifestyle
underlying
modifications
risk factors

Reduce risk
of ASCVD &
T2DM
Management – Lifestyle Modifications

Diet

Physical
Activity
Behavioral
Changes
Behavioral Changes

• Examples
• Set short and long term goals
• Create non-food related rewards
• Do not multitask when eating
• Calories count
• Monitor exercise, weight, and food
• Meal prep
• Stress reduction
• Motivational interviewing
Management – Lifestyle Modifications

Diet

Physical
Activity
Behavioral
Changes
Diet Changes
• Dietary Approaches to Stop
Hypertension (DASH)
• Limits foods high in saturated fat, sodium,
and sugar and has shown benefit in blood
pressure and LDL

• Vegetarian
• Mediterranean
• Plant based diet and limiting saturated fats
• Daily caloric intake
• Women: 1,200-1,500 kcal/day
• Men: 1,500-1,800 kcal/day

• Reduced daily caloric intake


• 500-1,000kcal/day= 1-2 lbs lost/week
• Do not recommend <800kcal/day
Management – Lifestyle Modifications

Diet

Physical
Activity
Behavioral
Changes
Physical Activity

Goal > 150 minutes/week divided Activities Calories Burned


between 3-5 days (30 min)
• 30 minutes 5 days/week
• 50 minutes 3 days/week Hiking 185
Dancing 165
Golfing 165
Stretching 90
Bicycling 145-295
Running 295
Swimming 255
Management

Managing
Lifestyle
underlying
modifications
risk factors

Reduce risk
of ASCVD &
T2DM
Containing Comorbidities

• ACC/AHA guidelines • ADA guidelines


• Goal BP <130/80 mmHg • Goal fasting BG
<80-130 mg/dL

Obesity

• ACC/AHA guidelines • ACC/AHA


• NLA guidelines guidelines
• Goal HDL>50 mg/dL • NLA guidelines
(female); • Goal TG<150 mg/dL
40 mg/dL (male)
Obesity
A condition characterized by the excessive
accumulation and storage of fat in the body.
2016

2015

2014

2013

2012

2011
Containing Comorbidities: Obesity

• In 2016, 1.9 billion adults


were overweight worldwide

• 600 million were obese


worldwide

• Indiana was ranked 10th


in incidence of obesity

NgM, Fleming T, Robinson M, et al. Lancet. 2014;384(9945): 766-781.


Containing Comorbidities: Obesity

Calories
Goals of Managing Obesity
7-10 % weight loss within 6-12 months
Decrease 500-1,000 calories per day
BMI Calculations

%&'()* ,-. ×012 %&'()* 7(


• 𝐵𝑀𝐼 = =
)&'()* 3 ('53 ) )&'()* 3 (83 )

BMI (kg/m2) Classification


≤18.9 Malnourished
19-24.9 Healthy
25-29.9 Overweight
30-39.9 Moderately Obese
≥40 Morbidly Obese
Patient Case
AC is a 58 YOWM with PMH of HTN,and T2DM

• Ht: 6’2” • Labs:


• Wt: 285 lbs • CrCl: 28 mL/min
• Fasting BG: 190 mg/dL
• Waist circumference: 41’’
• Lipids
• Vitals: • TC: 160 mg/dL
• HR: 75 bpm • TG: 131 mg/dL
• BP: 128/76 mmHg • HDL: 48 mg/dL
• Medications: • LDL: 101 mg/dL
• Losartan 100 mg PO daily
• Metformin 1000mg PO BID

What BMI classification does AC fall into?


Patient Case - BMI Calculation

%&'()* ,-. ×012 %&'()* 7(


• 𝐵𝑀𝐼 = =
)&'()* 3 ('53 ) )&'()* 3 (83 )

BMI (kg/m2) Classification


≤18.9 Malnourished
19-24.9 Healthy
25-29.9 Overweight
30-39.9 Moderately Obese
≥40 Morbidly Obese
Treatment Guidelines

AACE/ACE Management of Obesity


Diagnostic Categories Stage 0 Stage 1 Stage 2

Complications At least 1 mild to


At least 1 severe
(i.e. DM, HTN, HLD, CVD, PCOS) None moderate
complication
complication

1st line Treatment Lifestyle Changes Lifestyle Changes Lifestyle Changes

• Pharmacotherapy • Add Pharmacotherapy


• Pharmacotherapy
if lifestyle is not with a BMI at least 27
Adjunctive Therapy with a BMI at least
effective or BMI of • Bariatric surgery with a
27
30 or more BMI at least 35

Garvey T, Mechanick J, Bret E, et al. Endocr Prac 2016: 22; 1-203.


Patient Case
AC is a 58 YOWM with PMH of HTN and T2DM

• Ht: 6’2” • Labs:


• Wt: 285 lbs • CrCl: 28 mL/min
• Fasting BG: 190 mg/dL
• Waist circumference: 41’’
• Lipids
• Vitals: • TC: 160 mg/dL
• HR: 75 bpm • TG: 131 mg/dL
• BP: 128/76 mmHg • HDL: 48 mg/dL
• Medications: • LDL: 101 mg/dL
• Losartan 100 mg PO daily
• Metformin 1000mg PO BID

What stage would you classify AC’s metabolic syndrome?


Treatment Guidelines

AACE/ACE Management of Obesity


Diagnostic Categories Stage 0 Stage 1 Stage 2
At least 1 mild to
Complications At least 1 severe
None moderate
(i.e. DM, HTN, HLD, CVD, PCOS) complication
complication

1st line Treatment Lifestyle Changes Lifestyle Changes Lifestyle Changes

• Pharmacotherapy • Add Pharmacotherapy


• Pharmacotherapy
if lifestyle is not with a BMI at least 27
Adjunctive Therapy with a BMI at
effective or BMI • Bariatric surgery with a
least 27
of 30 or more BMI at least 35

Garvey T, Mechanick J, Bret E, et al. Endocr Prac 2016: 22; 1-203.


Initiation of Weight Loss Medications

Weight
Failed Related
Lifestyle Complications
Regained Therapy
Weight

MEDICATION THERAPY NEVER REPLACES


LIFESTYLE CHANGES!
Medications
Orlistat
• Rx: Xenical 120mg PO TID with meals
• OTC: Alli 60mg PO TID with meals

• Lipase inhibitor
• Decreases dietary fat by 30%

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more

• Pearls
• Take within 1 hour of each meal and skip dose if skipping meal
• Contraindicated in pregnancy, malabsorption syndrome, cholestasis, and
nephropathy
Lorcaserin
• Belviq 10mg PO BID

• Serotonin receptor agonist

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more

• Pearls
• After 12 weeks of use, if patient has not lost at least 5% of body weight medication
considered failed and should be discontinued
• Use in CrCl<30 mL/min is not recommended
• Caution with combination use of serotonin agonists due to risk of serotonin syndrome
Serotonin Syndrome

• Occurs with increased amount of serotonin in the bloodstream


• Usually seen if a patient is on multiple serotonin agonist or has renal
and/or hepatic impairment
• Symptoms include restlessness, confusion, tachycardia, hypertension,
muscle rigidity, diarrhea, and shivering
• More severe cases present with fever, seizures, arrhythmia, and
unconsciousness
• Due to the risk of serotonin syndrome, medications may require a
washout period or taper (example: 14 days) between the use of two or
more serotonin agonists
Sympathomimetic Agents
• Phendimetrazine (Bontril) IR 35 mg PO BID or TID
• Diethylpropion (Tenuate) IR 25 mg PO TID or 75mg PO daily

• Releases norepinephrine to decrease appetite and enhances satiety

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more

• Pearls
• Side effects: hypertension, palpitations, arrhythmias, and insomnia
• Monitor waist circumference and weight every month for 3 months

• Drug interactions
• Increase effect of anti-diabetic medications
• Risk of serotonin syndrome with serotonin agonists (example: SSRIs)
Sympathomimetic Agents: Phentermine
• Adipex-P ODT 15-30 mg PO QAM
• Lomaira IR 15-37.5 mg PO daily
• CrCl 15-30 mL/min max dose: 15mg PO daily

• Releases norepinephrine to decrease appetite and enhances satiety

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more

• Pearls
• Side effects: hypertension, palpitations, arrhythmias, and insomnia
• Monitor waist circumference and weight every month for 3 months

• Drug interactions
• Increase effect of anti-diabetic medications
• Risk of serotonin syndrome with serotonin agonists (example: SSRIs)
Sympathomimetic Agents: Phentermine

• Phentermine/topiramate (Qsymia) 3.75/23 mg PO daily for 14 days


• May increase to 7.5/46 mg PO daily
• If weight loss less than 3% after 12 weeks increase to 11.25/69 mg PO daily
• Max dose: 15/92 mg PO daily
• CrCl<50 mL/min or hepatic impairment: max dose of 7.5/46 mg PO daily

• Topiramate enhances GABA activity to decrease appetite


• Phentermine releases norepinephrine to decrease appetite and enhances
satiety

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more
Bupropion/Naltrexone
• Contrave 8/90 mg PO for 7 days, then increase to 8/90 mg PO BID for 7 days, then
16/180 mg PO QAM and 8/90 mg PO QPM for 7 days, then 16/180 mg PO BID

• Bupropion inhibits the reuptake of norepinephrine decreasing appetite


• Naltrexone is an opioid antagonist

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more

• Pearls
• Side effects: nausea, vomiting, dizziness, insomnia, dry mouth, diarrhea
• If weight loss less than 5% after 12 weeks of maintenance dose then discontinue

• Contraindications
• Uncontrolled HTN, seizure history, anorexia/bulimia history, or alcohol/drug withdrawal
Liraglutide
• Saxenda 0.6 mg SQ daily for 7 days then increase by 0.6 mg SQ every 7 days
• Max dose: 3 mg SQ daily

• Glucagon-like peptide-1 that slows gastric emptying

• Indication
• BMI of 27 or more with complications
• Complications include T2DM, HTN, HLD
• BMI of 30 or more

• Pearls
• Not to be confused for Victoza which is indicated for diabetes management at a lower
dose (maximum dose of 1.8 mg SQ daily)
• Side effects: nausea and diarrhea, hypoglycemia, tachycardia, and injection site
reaction

• Contraindications
• Pancreatitis and thyroid cancer
Medications Dose Side Effects Clinical Pearls Contraindication
Cramps, oily stool, Take within 1 hour of each meal Pregnancy,
Orlistat 60-120mg TID flatulence, urgency, Decreases absorption of vitamin K and malabsorption syndrome,
diarrhea contraceptive agents cholestasis, nephropathy

HA, dizziness, constipation, Increase serotonin syndrome in renal and


Lorcaserin 10mg BID
fatigue, dry mouth hepatic impairment

Phentermine/ HTN, palpitations, REMS: pregnancy test from the teratogenic


3.75/23mg daily x 14 days CKD
topiramate arrhythmia, insomnia effect of topiramate

HTN, palpitations, Interacts with DM medications. May need to MAOI require 14 day
Phendimetrazine 35mg BID-TID
arrhythmia, insomnia decrease DM dose washout

HTN, palpitations, Interacts with DM medications. May need to MAOI require 14 day
Diethylpropion I25mg TID
arrhythmia, insomnia decrease DM dose washout

Nausea, vomiting, dizziness, Uncontrolled HTN, seizure history,


Bupropion/ MAOI require 14 day
8/90mg daily insomnia, dry mouth, anorexia/bulimia, history of alcohol/drug
naltrexone diarrhea withdrawal
washout

Nausea and diarrhea,


Liraglutide REMS: pancreatitis Pancreatitis and thyroid
0.6mg daily hypoglycemia, tachycardia,
cancer
injection site reaction
Patient Case
AC is a 58 YOWM with PMH of HTN and T2DM

• Ht: 6’2” • Labs:


• Wt: 285 lbs • CrCl: 28 mL/min
• Fasting BG: 190 mg/dL
• Waist circumference: 41’’
• Lipids
• Vitals: • TC: 160 mg/dL
• HR: 75 bpm • TG: 131 mg/dL
• BP: 128/76 mmHg • HDL: 48 mg/dL
• Medications: • LDL: 101 mg/dL
• Losartan 100 mg PO daily
• Metformin 1000mg PO BID

Is AC a candidate for medication therapy? If so, what would you choose?


Questions