Pharmacologic Treatment Considerations for the Obese Patient Shala Swarm, FNP-BC Cheyenne Regional Medical Center Cheyenne Physicians Group Weight Loss.

Pharmacologic Treatment Considerations for the

Obese Patient

Shala Swarm, FNP-BCCheyenne Regional Medical Center

Cheyenne Physician’s Group

Weight Loss Center

No Disclosures

Objectives

• Identify three major Health Effects Obesity causes for patients and importance of addressing and treating obesity

• Select at least one treatment option for obesity for patients with major health conditions

Ideal Body and BMI

Ideal Body WeightMetropolitan Life Insurance Table

Method to Calculate

Women = 100 lbs for 5’0” +

5 lbs for each add. inch +/- 10%

Men = 110 lbs for 5’0” +

5 lbs for each add. Inch

+/- 10%

Body Mass IndexHeight to Weight Ratio

Method to Calculate

BMI = Weight (pounds) X 703

Height x Height

(inches)

Ideal Body Weight Charts

HEIGHT SMALL MEDIUM LARGE

(In Shoes)+ FRAME FRAME FRAME

Feet Inches      

5 2 128-134 131-141 138-150

5 3 130-136 133-143 140-153

5 4 132-138 135-145 142-156

5 5 134-140 137-148 144-160

5 6 136-142 139-151 146-164

5 7 138-145 142-154 149-168

5 8 140-148 145-157 152-172

5 9 142-151 148-160 155-176

5 10 144-154 151-163 158-180

5 11 146-157 154-166 161-184

6 0 149-160 157-170 164-188

6 1 152-164 160-174 168-192

6 2 155-168 164-178 172-197

6 3 158-172 167-182 176-202

6 4 162-176 171-187 181-207

TABLE 11999 METROPOLITAN HEIGHT AND WEIGHT TABLE

According to Frame, Ages 25-59MEN

Weight in Pounds (In Indoor Clothing)*

HEIGHT SMALL MEDIUM LARGE

(In Shoes)+ FRAME FRAME FRAME

Feet Inches      

4 10 102-111 109-121 118-131

4 11 103-113 111-123 120-134

5 0 104-115 113-126 122-137

5 1 106-118 115-129 125-140

5 2 108-121 118-132 128-143

5 3 111-124 121-135 131-147

5 4 114-127 124-138 134-151

5 5 117-130 127-141 137-155

5 6 120-133 130-144 140-159

5 7 123-136 133-147 143-163

5 8 126-139 136-150 146-167

5 9 129-142 139-153 149-170

5 10 132-145 142-156 152-173

5 11 135-148 145-159 155-176

6 0 138-151 148-162 158-179

TABLE 11999 METROPOLITAN HEIGHT AND WEIGHT TABLE

According to Frame, Ages 25-59WOMEN

Weight in Pounds (In Indoor Clothing)*

Indoor clothing weighing 5 pounds for men and 3 pounds for womenShoes with 1-inch heels

Source of basic data Build Study, 1979. Society of Actuaries and Association of Life Insurance Medical Directors of America, 1980.Copyright© 1996, 1999 Metropolitan Life Insurance Company

Courtesy of the Metropolitan Life Insurance Company.

Definitions of Overweight and Obesity

Normal Range – BMI 20-24.9

Overweight – BMI 25-29.9

Obese – BMI 30- 34.9

Severe Obese – BMI 35-39.9

Morbid Obese – BMI 40-49.9

Super Obese – BMI > 50

OBESITY IS A GROWING CONCERN

Obesity Trends* Among U.S. AdultsBMI > 30

Obesity Trends* Among U.S. Adults

Obesity Trends* Among U.S. Adults

Obesity Trends* Among U.S. Adults

Obesity Trends* Among U.S. Adults

Obesity Trends* Among U.S. Adults

StatisticsWorld

•Worldwide obesity has more than doubled since 1980.•In 2008, 1.5 billion adults, 20 and older, were overweight. Of these over 200 million men and nearly 300 million women were obese.•65% of the world's population live in countries where overweight and obesity kills more people than underweight.

Resource: World Health Organizationhttp://www.who.int/mediacentre/factsheets/fs311/en/

US

33.8 %

or one-third

of the

population

Resource: CDChttp://www.cdc.gov/obesity/data/trends.html#National

Wyoming

In 2010 was:

25.1 %

Resource: CDChttp://www.cdc.gov/obesity/data/trends.html#National

Risks of Obesity

Co-Morbid Medical Conditions

• Diabetes• Hypertension• Hyperlipidemia• Cardiac Disease• Sleep Apnea /

Hypoventilation• Liver disease• Cancer risk

• Heartburn• Asthma• Osteoarthritis• Depression• Urinary Incontinence• Menstrual Irregularity• Infertility• Leg Swelling

Complications of morbid obesity are LETHAL

Morbidly obese:

die 10 to 15 years earlier

0

1

2

3

4

20 25 30 35 40

Mort

ality

Rati

o

Body Mass IndexFontaine KR, Redden DT, Wang C, Westfall AO,Allison DB. Years of life lost due to obesity. JAMA. 2003;289:187-193.

What Causes Obesity

Environment ???• Decreased Mobility due

to increased access• Fast Food• Video Games• Sedentary Jobs

Genetics???• Takes many years

to these dramatic

changes

Weight Gain Cycle

Genetic Weight gain Environment

Appetite cravings

reduced energy expenditureMetabolic

Hormonal

Co-morbid disease

Other Causes

Medications:– Anti-psychotics– Anti-depressants– Anti-epileptic's– Steroids– Diabetes meds– Birth Control medications

Other Causes

Health Conditions– Endocrine Disorders– Hormonal Disorders– Sleep Apnea– Diabetes– Orthopedic Injuries

WHAT DO YOU DO WITH THESE PATIENTS?

How do you treat them?

Goals

• Long term vs Short term• Realistic• Small weight reduction can make a big

differenceo A good starting goal is 10% weight losso 10% weight loss can make a big impact on multiple health

conditions

• Prevent more weight gain

Treatment Options

• Screening Tests• Diet• Exercise• Psychological Evaluations• Medications• Surgery

Screening • History• Physical Exam• EKG• Special Measurements and Tests• Labs

CBC CMP Thyroid Panel (TSH, free T3, free T4) Lipid Profile UA Fasting Insulin, 2 hour post-prandial glucose 25 (OH) D levels

Diet

Calorie – a way to measure energy

Calories in = Calories out

1 Calorie = 1 kilocalorie = 1000 calories

Diet

Basal Metabolic rate (BMR)The energy used to sustain life (breathing, cell functions)

+

Thermic effect of food (TEF)Energy used to digest food

+

Activity Thermogenesis (AT)Energy used during exercises

and activities of daily living (NEAT)

Diet

BEE calculation (Harris-Benedict estimation)

BEE Females = 655.1 + (9.563 * Weight) + (1.85 * Height) - (4.676 * Age)

BEE Males = 66.5 + (13.75 * Weight) + (5.003 * Height) - (6.775 * Age)

Diet

Factors that Alter Metabolic Rate• Body Composition (leaner have higher BMR)• Age• Growth• Hormones• Stress• Temperature Changes• Fasting• Dieting• Caffeine, Alcohol, and Smoking

Diet

Increasing Metabolism• Regular Eating Habits• Exercise• Increasing muscle mass

DietFood Label

• RDA vs DV – – DV is a % based on a 2000 calorie diet – RDA is recommended daily allowance (guidelines to promote optimal

health to prevent deficiencies) These are not on the food label.

• Serving Size and amount per container • Calories• Protein• Sugars• Dietary Fiber

Diet• Protein 4 kcal/gm

DRI: 0.8gm/kg of IBW (Increased amounts needed to protect lean body mass in restricted calorie diets)

Growth and repair of body tissues

Sources: meat, fish, legumes, dairy, peanuts

• Carbohydrates 4 kcal/gmDRI: 130 gm/day

Energy Source

Sources: grains, fruits, vegetables

• Fat 9 kcal/gmAcceptable Ranges: 20-35% of daily kcal

Helps with digestion and absorption of fat soluble vitamins

Saturated, Monounsaturated, Polyunsaturated and Essential

• Alcohol 7 kcal/gmNo nutrient value

*DRI – Dietary References Intake

Diet

Keys to Success• Portions• Planning Ahead (meal planning and spacing of meals)• Protein• Conscious Eating• Liquid Calories vs Solid Food• Water Intake

Diets

Types of Diets• VLCD (very low calorie diets – 400-800 cal/day)

• LCD (low calorie diets – 800-1500 cal/day)

• Self Directed (Weight Watchers, Atkins)

DietVLCD• Medically Supervised• The lower the calories, the higher the protein

needed (1.2 g/kg women, 1.5 g/kg men)

• Short term• Vitamin Supplementation• Side Effects: GI, electrolyte, gout, psych, skin, neurological

• Contraindications: many

Diet

LCD• Medically Supervised• More compliance• Weekly Visits• Done by portion control, low-fat, low-carb, or

calorie counting

Diet

Protein and Weight Loss• Changes Body Composition by decreasing

body fat but protects lean tissue mass (protein synthesis in muscles and burning of calories)

• Stabilizes Blood Sugars (insulin levels)• Satiety

Reference: Layman

Diet

Protein Diets – Safety and Monitoring• UA• Vitamins

– Multi-vitamin– Calcium if needed– Vitamin D– Fish Oil

Physical Activity

• Exercise – planned activity• NEAT (non-exercise activity thermogensis)

Daily Activities

Exercise• Aerobic or Cardiovascular

Uses fatty acids for fuel

Cardiovascular fitness

Long bursts of activities

Oxygen dependant (breakdown of ATP)

• Anaerobic or ResistanceIntracellular glycogen as fuel

Improves lean body mass

Oxygen independent (lactic acid build-up)

Reference: Williams Circulation 2007

Exercise

Preventing Injury• Warm up and cool down and stretching

– Always warm up before stretching (optional)– Cool down (below target heart rate level) then stretch

• Body Recovery (resistance needs rest day)• Interval Training (not everyday)• Use guide – ACSM’s Guidelines for

Exercise Testing

Psychological Evaluation

• Eating Disorders• Emotional Eating (depression)• Stress• Eating Patterns• Being Overweight “protecting” patient• Support Systems

Meds, Meds, and more Meds

Medications

• Most are short term use only (but obesity is chronic)

• Safety • Addiction• Cost

**ALL MEDICATIONS NEED TO BE USED WITH BEHAVIORAL MODIFICATIONS OR THEY WILL NOT BE EFFECTIVE**

MedicationsRegulatory Challenges• Efficacy• Safety• Benefit-risk evaluation• History of obesity medications• Perception

MedicationsHistory of Obesity Medications

Drug Year Approved Year Removed

Short Term Use

Desoxyephedrine 1947 ??????

Phenmetrazine 1956 ??????

Phentermine 1959 Still On Market

Diethylpropion 1959 Still On Market

Phendimetrazine 1959 Still On Market

Benzphetamine 1960 Still On Market

Mazindol 1973 ??????

Fenfluramine 1973 1997

Long Term Use

Dexfenfluramine 1996 1997

Sibutramine 1997 2010

Orlistat 1999 Still On Market

http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4068B1_05_Approved-Drugs.htm

Medications

• Ephedrine (available as a restricted prescription medication)

• Phentermine (FDA approved 1957)

• Diethylpropion• Phendimetrazine• Benzphetrazine• Xenical• Merida (pulled off market fall 2010)

MedicationsEphedrine

• Dose Range 12.5-75 mg/day• Norepinephrine releaser• Used mainly for hypotension and bronchospasms• Ephedra was herbal form that was banned in 2004• Side Effects: tremors, nervousness, insomnia, increase HR and BP• Cautions/Contraindications: MAOI, breastfeeding, hyperthyroidism,

CAD, HTN, arrhythmias, CV disease, DM, glaucoma, seizures, renal

impairment, prolonged use

MedicationsPhenterminePhentermine HCL (Adipex-P, Fastin)

Phentermine Resin (Ionamin)

• Dose 15-37.5 mg/day• CNS Stimulate• Side Effects: palpitations, tachycardia, HTN, insomnia, dizziness,

euphoria, tremors, HA, pulmonary HTN, valvular heart disease, irritability• Cautions/Contraindications: CV disease, pregnancy and lactation, HTN,

hyperthyroidism, glaucoma, agitation, drug abuse, DM

MedicationsDiethylpropion (Tenuate)

• Dose Range: 25-75 mg/day• Similar to bupropion chemically• Side Effects: tachycardia, HTN, pulmonary HTN, valvular heart disease,

seizures, psychosis, hallucinations, leukopenia, constipation, dry

mouth, N/V, diarrhea, abdominal discomfort, anxiety, dizziness, HA,

insomnia, arrhythmias, palpitations• Caution/Contraindications: pulmonary HTN, HTN, arteriosclerosis,

hyperthyroidism, glaucoma, agitations, drug abuse, valvular hear

disease, heart murmur, CV disease, seizure disorder, psychiatric

disorder

MedicationsPhendimetrazine (Bontril)

• Dose Range: 35-105 mg/day• Mechanism of action unknown, CNS stimulant• Side Effects: tachycardia, HTN, pulmonary HTN, restlessness,

agitation, tremor, flushing, sweating, blurred vision, constipation,

nausea, diarrhea, gastric pain, anxiety, dizziness, HA, insomnia,

palpitations, urinary frequency • Caution/Contraindications: pulmonary HTN, HTN, arteriosclerosis,

hyperthyroidism, glaucoma, agitation, drug abuse, valvular hear

disease, heart murmur, CV disease, DM

MedicationsBenzphetamine (Didrex)

• Dose Range: 25-50 mg/day• Mechanism of action unknown, CNS stimulant• Side Effects: psychosis, tachycardia, HTN, cardiomyopathy, cardiac

ischemia, restlessness, agitation, tremor, flushing, sweating,

constipation, nausea, diarrhea, dizziness, HA, dry mouth, insomnia,

unpleasant taste, palpitations, urinary frequency • Caution/Contraindications: HTN, arteriosclerosis, hyperthyroidism,

glaucoma, agitation, drug abuse, valvular hear disease, heart murmur,

CV disease, DM, arrhythmias

MedicationsXenical (Orlistat, Alli)

• Dose Range: 60-120 mg TID• Mechanism of action: inhibits gastric and pancreatic lipases, reducing

fat absorption• Side Effects: angioedema, fat-soluble vitamin deficiency,

hepatotoxicity; oily spotting flatus with discharge, fecal urgency, fatty

stools, oily evacuation, fecal incontinence, URI, influenza, HA,

abdominal pain, back pain, nausea, menstrual irregularities, UTI,

fatigue, arthritis, rectal pain, dizziness, infectious diarrhea• Caution/Contraindications: malabsorption syndromes, cholestasis,

eating disorders• Kidney and Pancreas problems???

Medications

Off Label Use • Antidepressants• Insulin Sensitizers• Anti-Seizures• Combination Therapy• 5-HTP / Carbidopa

Medications

5-HTP = 5-hydroxytryptophanIncreases the production of serotoninOver the counterWide margin of safety Not been associated risk for serotonin syndrome Does not alter cardiovascular parametersRapidly Metabolized by peripheral decarboxylase

Medications

5-HTP = 5-hydroxytryptophanOther Uses: anxiety, depression, alcohol withdrawal, headaches

Side Effects: anorexia, diarrhea, dizziness, drowsiness, eosinophilia,

flatulence, N/V, somnolence, palpitations, insomnia, hypomania, stomach pain, taste disturbance, weight gain

Avoid Use: eosinophilia syndromes, MAOI use, mitochondrial

encephalomyopathy

Caution in: antidepressant use, down syndrome, GI disorders, platelet

disorders, psychiatric disorder history, PUD, renal disease

Medications

AntidepressantsSSRI (selective serotonin reuptake inhibitors) – Increase 5-HT (serotonin) in

the satiety center and down regulate 5-HT2A auto-receptors which increase 5-HT (serotonin) secretion

– Side Effects: dry mouth, insomnia, nausea, tremor, headache, sweating, decreased libido, Serotonin Syndrome

– Weight Loss Success: Limited results, but may be helpful for emotional eating or night time eating syndrome (sertraline)

Medications

AntidepressantsBupropion (Wellbutrin) – Inhibits neuronal uptake of norepinephrine and dopamine

– Chemically like diethylpropion– Side Effects: dry mouth, headache, agitation, nausea, dizziness, constipation,

tremor, sweating, abnormal dreams, insomnia, tinnitus, diarrhea, abdominal pain, anxiety

– Weight Loss Success: Can decrease appetite and cravings

Medications

Insulin SensitizersMetformin (Glucophage)

• Indicated for Diabetes Type 2• Mechanism of Action: decreases hepatic glucose production and

intestinal glucose absorption; increases insulin sensitivity and

peripheral glucose uptake• Side Effects: nausea, diarrhea, flatulence, anorexia, headache,

metallic taste

Medications

Insulin SensitizersByetta (exenatide)

Victoza (liraglutide)

• Indicated for Diabetes Type 2• Mechanism of Action: activates glucagon-like-peptide-1 (GLP-1)

receptor, increasing insulin secretion, decreasing glucagon secretion,

and delaying gastric emptying (incretin mimetic)• Side Effects: nausea, vomiting, diarrhea, nervousness, dizziness,

headache, dyspepsia, decreased appetite

Liraglutide contraindicated in pancreatitis and thyroid carcinoma

Medications

Anti-Seizure MedicationsTopiramate (Topamax)

• Indicated for Seizures and Migraine headaches• Mechanism of Action: modulated GABA-A receptors, weak caronic

anhydrase inhibitor, exhibits state-dependent bloackade of voltage-

dependant Na and Ca channels• Side Effects: dizziness, parathesias, fatigue, difficulty concentrating,

somnolence, weight loss, nervousness, ataxia, diarrhea, nausea,

nystagmus, tremor, fever, taste changes, taste changes, myopia,

nephrolithiasis• Contraindications: increased intraocular pressure

Medications

Others for thought• Probiotics ???• Antibiotics ???• Vitamin D ???

Medications

Combination Therapy

Obesity is a chronic medical condition and just like any other chronic medical condition multiple medications are usually necessary to proper control of the health condition.

Example: HTN, Diabetes

Medications

Combined Medications

Phentermine + 5-HTP/carbidopa• 5-HTP and carbidopa can counteract side effects of phentermine• Dual action with NE release (phentermine) and increased 5-HT

release • Dual mechanism can increase satiety and decrease food craving

Dosing

Phentermine dosing + compounded 5-HTP / carbidopa

5-HTP = 5-25 mg

carbidopa = always 5 mg

Medications

Combination Medications

Both phentermine and wellbutrin

have norepinephrine effects

and therefore recommended

not to use them together

MedicationsWhat may be to come

• Naltrexone + bupropion (Contrave) – rejected by the FDA in February 2011 (Orexigen)

• Topiramate + phentermine (Qnexa) – (Vivus)

• Zonesamide + bupropion (Empatic) – (Orexigen)

• Pramlintide + metreleptin – Amylin Pharmaceuticals

• Lorcaserin (expected to be named Lorqess) - Arena Pharmaceuticals

• Tesofensine - NeuroSearch

• Liraglutide • Exenatide• GLP-1 + PYY 3-36 – Emisphere Technologies

Medications

Thoughts for Research• Safety• Satiety• Side Effects• Long Term• Cost• Look at gut hormones instead of CNS

Thoughts for the Future

Orexigens• Neuropeptide Y (NPY)• Agouti-related protein (AgRP)• Orexin A and B• Melanin-concentrating hormone (MCH)• Ghrelin (activates NPY and AgRP)

Anorexigens• Brain-derived neurotrophic factor • Alpha-melanocyte stimulating hormone

(alpha-MSH)• Pro-opiomelanocortin (POMC)• Serotonin• Cocaine-amphetamine-regulating transcript

(CART)• Leptin ***• Insulin ***

*** Inhibit NPY and AgRP

Other Thoughts

• Need for a safe anti-obesity medication for long term use as obesity is a chronic condition; Short term control is not useful

• Medications should always be used with diet, exercise and behavioral modification changes

• Should get informed consent

Medications

What not to prescribe – HCG dietASBP Statement on HCG diet:

1. The Simeons method for weight loss is not recommended.

2. The Simeons diet is not recommended.

3. The use of HCG for weight loss is not recommended.

ASBP Position Statement on HCG Diet:

http://www.asbp.org/siterun_data/about_asbp/position_statements/doc5858839311268715587.html

Weight Loss Surgery Options

Weight Loss SurgeryGastric restrictive Malabsorptive

1. JI bypass

2. Bilio Pancreatic Bypass

3. Duodenal Switch

4. Gastric Bypass • Long Limb

1. Vertical Banded

Gastroplasty2. Gastric Bypass

3. Gastric Sleeve

4. Gastric Band

Gastric BypassR o u x – e n - Y

Gastric Sleeve L A P A R O S C O P I C

Gastric Band System

How heavy is the average weight loss surgery patient?

Typical Weight Loss surgery patient

Weight Range (pounds)

Nu

mb

er

In E

ach

Ran

ge

Weight Loss Surgery

Candidates for Surgery• BMI >40• BMI >35 with significant co-morbidities• H&P to assess need for cardiac/pulmonary

clearances• Psychological Evaluation• Dietary Screening

Gastric restrictive Malabsorptive

1. JI bypass

2. Bilio Pancreatic Bypass

3. Duodenal Switch

4. Gastric Bypass • Long Limb

1. Vertical Banded

Gastroplasty2. Gastric Bypass

3. Lap Band

Gastric BypassR o u x – e n - Y

Gastric restrictive Malabsorptive

1. JI bypass

2. Bilio Pancreatic Bypass

3. Duodenal Switch

4. Gastric Bypass • Long Limb

1. Vertical Banded

Gastroplasty2. Gastric Bypass

3. Lap Band

Gastric BypassR o u x – e n - Y

Weight Loss SurgeryMal-absorptive Procedures

JI Bypass • Performed from 1950s-1970s• Problems / Complications:

mineral and electrolyte imbalances, protein malnutrition, abdominal discomfort including flatus and diarrhea, liver disease, renal disease, peripheral neuropathy, pericarditis, and more.

BPD / DS• More demanding operation than

the RYGB• Problems / Complications:

diarrhea, foul smelling flatulence, mal-absorption of fat soluble vitamins, protein malnutrition, ulcers, and dumping syndrome.

Gastric Restrictive Procedures

Gastric Restrictive Procedures

B12iron

Ca++

Protein calorie malnutrition

Dehydration

Gastric Restrictive Procedures

Ghrelin receptors

Gastric Sleeve L A P A R O S C O P I C

Gastric BypassR o u x – e n - Y

2nd stage

Gastric Restrictive Procedure

http://asmbs.org/benefits-of-bariatric-surgery/

Weight Loss SurgeryRisks of Surgery

• Complications may include– Mortality (0.24%)– Staple line leaks (RYGB) (0.73%)– PE (0.25%)– DVT (0.17%)– Wound infections (1.8%)– Marginal ulcers– Malnutrition– GI Bleed (0.44%)– Small Bowel Obstruction (0.40%)

Weight Loss SurgerySafety and Monitoring

Routine lifetime follow up• Lap Band: monthly for 6 months and fills

based on symptoms but routine visits for life

• RYGB and Sleeve: 1 week, 1 month, 3 month, 6 months, 9 months, 1 year, 18 months, and annually

• Regular follow up visits help with compliance and better weight loss

Weight Loss Surgery

Safety and Monitoring

Vitamin Supplementation• Bands – multi-vitamin, calcium, fish oil• RYGB / Sleeve – multi-vitamin (bariatric),

calcium, B12, iron, fish oil

Weight Loss Surgery

Routine Labs• Bands – general health screening

(annually)• RYGB / Sleeves – CBC, CMP, folate,

thiamine, B12, total iron, TIBC, ferritin, A1C, lipids, vitamin D, TSH– Annual bone density

Weight Loss Surgery

Diet• Slow diet progression• Food Intolerances• No No Foods• Eating Behaviors that need changed

Weight Loss Surgery

DO NOT

• Prescribe NSAIDS after RYGB• Prescribe steroids after RYGB• Prescribe extended release medications

after RYGB• SMOKE

NIH Consensus

Severe obesity is a

Chronic, intractable, and progressive disorder;

any therapeutic program must, therefore, be

lifelong.

References1. National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI) North American Association for the Study of Obesity. The

practical guide: identification, evaluation, and treatment of overweight and obesity in adults. NIH; 2000; NIH Publication No. 00-4084.

2. National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. NIH; 1998; NIH Publication No. 98-4083.

3. Center for Disease Control. Overweight and Obesity. http://www.cdc.gov/obesity/data/trends.html

4. Center for Disease Control. Overweight and Obesity. http://www.cdc.gov/obesity/data/trends.html#National

5. World Health Organization. Overweight and Obesity. http://www.who.int/mediacentre/factsheets/fs311/en/

6. Build Study, 1979. Society of Actuaries and Association of Life Insurance Medical Directors of America, 1980.

7. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003 Jan 8;289(2):187-93.

8. Knight JA. Diseases and disorders associated with excess body weight. Ann Clin Lab Sci. 2011 Spring;41(2):107-21.

9. American Society of Bariatric Physicians (ASBP). Bariatric Practice Guidelines. 2004.

10. American Society of Bariatric Physicians (ASBP). Position statement on HCG diet. http://www.asbp.org/siterun_data/about_asbp/position_statements/doc5858839311268715587.html

11. Millward D, Layman D, et. al. Protein quality assessment: impact of expanding understanding of protein and amino acid needs for optimal health. AJCN 2008 May; 87, (5), 1576S-1581S.

12. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

13. Shai I, et. al, Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008 Jul 17;359(3):229-41.

14. Sacks FM, et. al, Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009 Feb 26;360(9):859-73

15. Mahan L.K, and Escott-Stump, 2000. S. Krause’s Food, Nutrition, & Diet Therapy. 11th ed. Philadelphia, Pennsylvania. Elsevier

16. Epocrates Rx Version 1.371.0. San Mateo (CA): Epocrates, Inc.

17. Food and Drug Administration. FDA Approved obesity drugs. http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4068B1_05_Approved-Drugs.htm

18. Heal, D. Gosden, J. and Smith S. 2009. Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders. BJCP 68:6: 861-874.

19. Hussain, SS and Bloom SR. The pharmacological treatment and management of obesity. Postgrad Med. 2011 Jan: 123 (1): 34-44.

20. Cooke, D and Bloom S. The obesity pipeline: current strategies in the development of anti-obesity drugs. Nat. Rev Drug Discov. 2006 Nov: 5(11): 919-31.

21. Kaplan LM. Pharmacologic therapies for obesity. Gastroenterol Clin North Am. 2010 Mar: 39 (1): 69-79.

References Cont.1. Kootte RS, et. al; The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab. 2011

Aug.2. Ly, NP et. al.; Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol.

2011. May; 127 (5): 1087-94.3. Weir Ma, Beyea MM, Gomes T., et. al. Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med. 2011 Apr 11;171(7):703-4.4. Brethauer SA, Chand B, Schauer PR. Risks and benefits of bariatric surgery: current evidence. Cleveland Clinic Journal of Medicine (2006)

75(11); 993-1007.5. Anonymous. Perioperative safety in the longitudinal assessment of bariatric surgery. NEJM. 2009 Jul; 361(5) 445.6. Goutham RAO. Office-based strategies for the management of obesity. Am Fam Physician. 2010 Jun 15; 81(12): 1449-1455.7. American Society of Bariatric Surgery (ASMBS). Rational for surgical treatment. http://asmbs.org/rationale-for-surgical-treatment/8. Gastrointestinal Surgery for Severe Obesity. NIH Consensus Statement 1991 Mar 25-27;9(1):1-20. 9. Goldstein DJ, Rampey AH Jr, Roback PJ, Wilson MG, Hamilton SH, Sayler ME, Tollefson GD. Efficacy and safety of long-

term fluoxetine treatment of obesity--maximizing success. Obes Res. 1995 Nov;3 Suppl 4:481S-490S.10. Stunkard AJ, Allison KC, Lundgren JD, Martino NS, Heo M, Etemad B, O'Reardon JP. A paradigm for facilitating pharmacotherapy at a distance:

sertraline treatment of the night eating syndrome. J Clin Psychiatry. 2006 Oct;67(10):1568-72.11. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003; 289:187-193.12. AACE/TOS/ASMBS Bariatric Surgery Guidelines, Endocr Pract. 2008;14 (Supp 1)