Management of the Management of the Morbidly ObeseMorbidly Obese

Sarah Nelson, Pharm.D. Sarah Nelson, Pharm.D.

Pharmacy Practice ResidentPharmacy Practice Resident

ObjectivesObjectives

Describe the proposed origins of obesityDescribe the proposed origins of obesity

Discriminate between current treatment Discriminate between current treatment options for obesityoptions for obesity

Examine the effects following bariatric Examine the effects following bariatric surgerysurgery

Distinguish dynamic and kinetic Distinguish dynamic and kinetic differences in obese patientsdifferences in obese patients

Definition of ObesityDefinition of Obesity

An imbalance between energy intake An imbalance between energy intake and energy expenditureand energy expenditure

Consumption of calories which Consumption of calories which exceeds that required for the resting exceeds that required for the resting metabolic rate and active energy metabolic rate and active energy expenditureexpenditure

Energy equation:Energy equation:Intake (food) = expenditure + storageIntake (food) = expenditure + storage

Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.

Classification of Body Classification of Body WeightWeight

Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.

BMI (kg/mBMI (kg/m22)) Weight CategoryWeight Category

<18.5<18.5 UnderweightUnderweight

18.5-24.918.5-24.9 Normal weightNormal weight

25.0-29.925.0-29.9 OverweightOverweight

30.0-34.930.0-34.9 Class I ObesityClass I Obesity

35.0-39.935.0-39.9 Class II ObesityClass II Obesity

≥≥4040 Class III ObesityClass III Obesity

BackgroundBackground

Obesity recognized as a marker for Obesity recognized as a marker for mortality in the 1960’smortality in the 1960’s– Analysis of life insurance redemptionAnalysis of life insurance redemption

Mortality lowest when BMI 20-25Mortality lowest when BMI 20-25 Mortality dramatically increased when BMI >35Mortality dramatically increased when BMI >35 Mortality also increased when BMI <20Mortality also increased when BMI <20

In 2000, WHO declared obesity as the In 2000, WHO declared obesity as the greatest health threat facing the Westgreatest health threat facing the West

Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.

Prevalence of Weight Prevalence of Weight DisordersDisorders

1.6 billion individuals are overweight1.6 billion individuals are overweight– Highest in United StatesHighest in United States

2 out of 3 Americans are overweight2 out of 3 Americans are overweight– ½ of all overweight Americans are obese½ of all overweight Americans are obese– BMI ≥ 35 kg/mBMI ≥ 35 kg/m22: 23 million Americans: 23 million Americans– BMI ≥ 40 kg/mBMI ≥ 40 kg/m22: 8 million Americans: 8 million Americans

Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737

Effects of Weight DisordersEffects of Weight Disorders

Major cause of preventable deathMajor cause of preventable death

– >100,000 deaths per year>100,000 deaths per year

– $70 billion health care dollars per year$70 billion health care dollars per year

– 10% of national healthcare expenditure10% of national healthcare expenditure

Pieracci F, Barie P, Pomp A. Critical care of the bariatric patient. Crit Care Med. 2006;34: 1796-1804

In a Decade . . . In a Decade . . .

http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm

Effects of ObesityEffects of Obesity

Increase in prevalence of co-Increase in prevalence of co-morbiditiesmorbidities– Diabetes Mellitus Type 2Diabetes Mellitus Type 2– Heart Disease (HTN, XOL, stroke)Heart Disease (HTN, XOL, stroke)– Obstructive sleep apneaObstructive sleep apnea– Weight-bearing degenerative disordersWeight-bearing degenerative disorders– DepressionDepression– CancerCancer

Decreased life expectancyDecreased life expectancyBuchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737

Obesity and DiabetesObesity and Diabetes

Increase in circulating free fatty acids Increase in circulating free fatty acids competes with circulating glucose competes with circulating glucose elevated insulin secretion and elevated insulin secretion and resistanceresistance

Resistin, adiponectin, and TNF-Resistin, adiponectin, and TNF-αα interact with insulin to generate insulin interact with insulin to generate insulin resistanceresistance

Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.http://www.nature.com/nrm/journal/v9/n5/images/nrm2391-f2.jpg

Origins of ObesityOrigins of Obesity

Origins of ObesityOrigins of Obesity

GeneticGenetic

Environmental/BehavioralEnvironmental/Behavioral

Regulation of Energy Regulation of Energy BalanceBalance

Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.

Genetic EffectsGenetic Effects

Gene deletions/mutationsGene deletions/mutations– Leptin deficiency/leptin receptor Leptin deficiency/leptin receptor

modificationmodification

– MC4R deficiencyMC4R deficiency Most common monogenic disorder to dateMost common monogenic disorder to date Present in 1-6% of obese individualsPresent in 1-6% of obese individuals

– GAD65 over-expressionGAD65 over-expression Increases production of GABA Increases production of GABA increased increased

food intakefood intakeBell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.

Genetic EffectsGenetic Effects

Syndromic association Syndromic association – >20 syndromes caused by genetic >20 syndromes caused by genetic

defects or chromosome abnormalities defects or chromosome abnormalities are characterized by obesityare characterized by obesity Most are in the setting of mental retardationMost are in the setting of mental retardation Prader-Willi syndromePrader-Willi syndrome Pseudohypoparathyroidism type 1APseudohypoparathyroidism type 1A Bardet-Biedl syndrome Bardet-Biedl syndrome

Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.

Genetic EffectsGenetic Effects

Genetics of common obesityGenetics of common obesity– 1977 NHLBI Twin Study 1977 NHLBI Twin Study familial obesity familial obesity

due to genetic factors rather than due to genetic factors rather than environmentenvironment Estimated heritability value of 0.81 upon 25 Estimated heritability value of 0.81 upon 25

year follow upyear follow up

– Adoption StudiesAdoption Studies Adopted children have body sizes more similar Adopted children have body sizes more similar

to biologic parents rather than adopted to biologic parents rather than adopted parentsparents

Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.Stunkard A, Sorenson T, Hanis C, et al. An adoption study of human obesity. JAMA. 1986;314:193-198.

EnvironmentalEnvironmental

LocationLocation– Access to walk paths, recreational Access to walk paths, recreational

facilities, etc.facilities, etc.– Access to fast food restaurants, Access to fast food restaurants,

supermarkets, health-related storessupermarkets, health-related stores

Socioeconomic status (SES)Socioeconomic status (SES)– Inverse relationship between individual Inverse relationship between individual

and area-level SES and weightand area-level SES and weightHarrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.

EnvironmentalEnvironmental

Results from the Ontario Heart Health Results from the Ontario Heart Health Surveys (OHHS) demonstrate an Surveys (OHHS) demonstrate an increase in obesity with:increase in obesity with:– Increased age (females>males)Increased age (females>males)– Absence of high school educationAbsence of high school education– Adoption of a sedentary lifestyleAdoption of a sedentary lifestyle

Nicotine consumption was a negative Nicotine consumption was a negative risk factor for obesity in the OHHS risk factor for obesity in the OHHS populationpopulation

Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.

Treatment Options for Treatment Options for ObesityObesity

Treatment Options for Treatment Options for ObesityObesity

Diet TherapyDiet Therapy

Pharmaceutical AgentsPharmaceutical Agents– SibutramineSibutramine– OrlistatOrlistat– BupropionBupropion– Potential targetsPotential targets

Surgical TherapySurgical Therapy– Gastric BandingGastric Banding– Gastric BypassGastric Bypass– Biliopancreatic diversionBiliopancreatic diversion

Sibutramine (MeridiaSibutramine (Meridia®®)) MOA: inhibits norepinephrine (NE) and MOA: inhibits norepinephrine (NE) and

serotonin (5-HTserotonin (5-HT22) neuronal uptake ) neuronal uptake enhances satietyenhances satiety

Dose: 10 mg PO once daily x 4 wks, then Dose: 10 mg PO once daily x 4 wks, then may may to 15 mg daily x 100 wks to 15 mg daily x 100 wks

Adverse Effects (>10%)Adverse Effects (>10%)– HeadacheHeadache– InsomniaInsomnia– XerostomiaXerostomia– ConstipationConstipation

Chaput JP, Tremblay A. Current and novel approaches to the drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.

Sibutramine (MeridiaSibutramine (Meridia®®))

Bray et al. (1999)Bray et al. (1999)

nn Dose Dose (mg)(mg)

Mean wt Mean wt reduction reduction (kg)(kg)

>5% wt loss >5% wt loss (%)(%)

>10% wt loss (%)>10% wt loss (%)

8787 PlaceboPlacebo 1.31.3 19.519.5 00

9595 11 2.42.4 25.325.3 10.510.5ҰҰ

107107 55 3.73.7 37.437.4ҰҰ 12.1*12.1*

9999 1010 5.75.7 59.6*59.6* 17.2*17.2*

9898 1515 7.07.0 67.3*67.3* 34.7*34.7*

9696 2020 8.28.2 71.9*71.9* 36.5*36.5*

101101 3030 9.09.0 77.2*77.2* 46.5*46.5*

Bray G, Blackburn G, Ferguson J et al. Sibutramine produces dose-related weight loss. Obes Res. 1999;7:189-98.

STORM TrialSTORM Trial

Randomized, double-blind, placebo Randomized, double-blind, placebo controlled trialcontrolled trial

Effect of weight maintenance after Effect of weight maintenance after weight lossweight loss

All patients on a 600 kcal/day deficit All patients on a 600 kcal/day deficit dietdiet

James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.

STORM TrialSTORM Trial

James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.

Sibutramine (MeridiaSibutramine (Meridia®®))

Use with caution in patients on Use with caution in patients on concurrent serotonergic medicationsconcurrent serotonergic medications risk of serotonin syndromerisk of serotonin syndrome– Previous black box warningPrevious black box warning

Use with caution in patients with Use with caution in patients with uncontrolled hypertensionuncontrolled hypertension– 12.5% patients 12.5% patients in BP by 15 mmHg in BP by 15 mmHg

Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.

BupropionBupropion

MOA: inhibits NE and DA neuronal uptake MOA: inhibits NE and DA neuronal uptake enhances satiety enhances satiety

Dose: 300 to 400 mg dailyDose: 300 to 400 mg daily

Non-FDA approved indicationNon-FDA approved indication

Contraindicated in patients with seizure Contraindicated in patients with seizure disordersdisorders

Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-weekdouble-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.

BupropionBupropion

Anderson et al. (2002)Anderson et al. (2002)

24 week RDBPC parallel-group study24 week RDBPC parallel-group study

Compared placebo, 300 mg, & 400 mg Compared placebo, 300 mg, & 400 mg dailydaily

Calorie restricted diet & lifestyle Calorie restricted diet & lifestyle intervention program initiatedintervention program initiated

Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-weekdouble-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.

BupropionBupropion

Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-weekdouble-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.

Orlistat (AlliOrlistat (Alli®®, Xenical, Xenical®®))

MOA: reversible inhibitor of gastric MOA: reversible inhibitor of gastric and pancreatic lipases and pancreatic lipases decreases decreases dietary fat absorptiondietary fat absorption

Only FDA approved drug that directly Only FDA approved drug that directly alters metabolismalters metabolism

Dose: 120 mg TID with mealsDose: 120 mg TID with meals

Davidson et al. (1999)Davidson et al. (1999)

2-year DBRPC study2-year DBRPC study

Diet modified to ensure adequate fat Diet modified to ensure adequate fat intakeintake

Orlistat (Alli®, Xenical®)Orlistat (Alli®, Xenical®)

Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.

Orlistat (Alli®, Xenical®)Orlistat (Alli®, Xenical®)

Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.

Concerns with orlistat:Concerns with orlistat:

in fat-soluble vitamin deficiencyin fat-soluble vitamin deficiency

– Gastrointestinal adverse effects commonGastrointestinal adverse effects common Fatty/oily stool (20%)Fatty/oily stool (20%) Oily spotting (26.6%)Oily spotting (26.6%) Fecal incontinence (7.7%)Fecal incontinence (7.7%) Fecal urgency (22.1%)Fecal urgency (22.1%) Flatulence with discharge (23.9%)Flatulence with discharge (23.9%)

Orlistat (Alli®, Xenical®)Orlistat (Alli®, Xenical®)

Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.

Other MedicationsOther Medications

MetforminMetformin– 1700 mg daily 1700 mg daily 300 kcal intake 300 kcal intake

reduction/30-minute eating periodreduction/30-minute eating period hunger ratingshunger ratings

TopiramateTopiramate– 65.2% of patients had weight loss of 0.5 65.2% of patients had weight loss of 0.5

kg to 19.5 kg in migraine studykg to 19.5 kg in migraine study– 200 mg daily 200 mg daily average body weight average body weight

5.9 kg5.9 kg

Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.

Future Pharmacologic Future Pharmacologic AgentsAgents

Recombinant human leptinRecombinant human leptin

Neuropeptide Y antagonistsNeuropeptide Y antagonists

GLP-1GLP-1

Ghrelin antagonistsGhrelin antagonists

Endocannabinoid receptor antagonistsEndocannabinoid receptor antagonists

Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.

RimonabantRimonabant

MOA: CBMOA: CB11 receptor antagonist receptor antagonist

Dose: 20 mg dailyDose: 20 mg daily

Adverse Effects: suicidal ideation, anxiety, Adverse Effects: suicidal ideation, anxiety, depressiondepression

Not available in USNot available in US– NDA withdrawnNDA withdrawn

RIO TrialsRIO Trials

EfficacyEfficacy– Decreased body Decreased body

weight (-6.6 kg)weight (-6.6 kg)– Decreased waist Decreased waist

circumference (-3.9 circumference (-3.9 cm)cm)

– Decreased BP (-1.8 Decreased BP (-1.8 mmHg SBP)mmHg SBP)

– Decreased A1c (0.7%)Decreased A1c (0.7%)– No decrease in LDL, No decrease in LDL,

total cholesteroltotal cholesterol

SafetySafety– RR 1.9 for any RR 1.9 for any

psychiatric disorderpsychiatric disorder– 2.5x more likely to 2.5x more likely to

discontinue discontinue medication due to medication due to depressiondepression

Idelevich E, Kirch W, Schlinder C. Current pharmacotherapeutic concepts for the treatment of obesity in adults. Therapeutic Advances in Cardiovascular disease. 2009;3:75-90.

LeptinLeptin

Peptide that acts on the hypothalamus Peptide that acts on the hypothalamus to modulate body weight, intake and to modulate body weight, intake and fat storesfat stores

Leptin deficiency Leptin deficiency early onset early onset obesityobesity

Treatment options:Treatment options:– Leptin analogues > native leptinLeptin analogues > native leptin– Leptin gene promotersLeptin gene promoters

CNTF may also potentiate leptin-like CNTF may also potentiate leptin-like effectseffects

Chaput J, Tremblay A. Current and novel approaches to drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.

Bariatric SurgeryBariatric Surgery

Only option for treatment of morbidly obeseOnly option for treatment of morbidly obese

20-fold increase in procedures in last 10 20-fold increase in procedures in last 10 yearsyears

Types of surgeryTypes of surgery– RestrictiveRestrictive– MalabsorptiveMalabsorptive– CombinationCombination

Steinbrook R. Surgery for severe obesity. NEJM. 2004;350:1075-79.Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.

Gastric BypassGastric Bypass

Restrictive and malabsorptiveRestrictive and malabsorptive– Causes early satiety and incomplete nutrient Causes early satiety and incomplete nutrient

digestion and absorptiondigestion and absorption

Roux-en-Y surgery Roux-en-Y surgery – Creation of 15-30 cm gastric pouchCreation of 15-30 cm gastric pouch– Connection of jejunum to gastric curvatureConnection of jejunum to gastric curvature

Bypasses portion of stomach, duodenum, and portion of Bypasses portion of stomach, duodenum, and portion of jejunumjejunum

Most common bariatric surgeryMost common bariatric surgerySalameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.

Gastric BypassGastric Bypass

ComplicationsComplications– Mortality rate: 0.5%Mortality rate: 0.5%– Early complications: anastomotic leak, Early complications: anastomotic leak,

PE, infectionPE, infection– Late complications: strictures, bowel Late complications: strictures, bowel

obstruction, malnutrition, dumping obstruction, malnutrition, dumping syndromesyndrome

OutcomesOutcomes– 62-68% excess weight loss at 2 years62-68% excess weight loss at 2 years

Initial weight loss of 70-80% excess weightInitial weight loss of 70-80% excess weight Regain of weight after 2 years is commonRegain of weight after 2 years is commonSalameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.

Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.

Gastric BandingGastric Banding

Restrictive procedureRestrictive procedure

Implantation of inflatable silicone band Implantation of inflatable silicone band around the upper stomacharound the upper stomach

Band adjustments are based on Band adjustments are based on individual weight loss and appetiteindividual weight loss and appetite– Adjustments required 5-6 times in 1Adjustments required 5-6 times in 1stst year year

Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.

Gastric BandingGastric Banding

ComplicationsComplications– Safest bariatric procedure available Safest bariatric procedure available – Mortality rate: 0.05-0.1%Mortality rate: 0.05-0.1%– Late complications: gastric prolapse, band Late complications: gastric prolapse, band

erosion, port infection, tubing problemserosion, port infection, tubing problems OutcomesOutcomes

– Weight loss is gradualWeight loss is gradual– 57% excess weight loss after 6 years57% excess weight loss after 6 years

Direct correlation with motivation and follow-Direct correlation with motivation and follow-upup

Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.

Banding vs. BypassBanding vs. Bypass

Pt characteristic (%)Pt characteristic (%) Gastric Banding Gastric Banding (n=160)(n=160)

Gastric BypassGastric Bypass

(n=232)(n=232)

Weight lossWeight loss 3434 6464

DiabetesDiabetes 7777 7272

HypertensionHypertension 5656 6666

DyslipidemiaDyslipidemia 3737 4848

OsteoarthritisOsteoarthritis 8484 7575

Short term Short term complicationcomplication

5.25.2 3.33.3

Long term Long term complicationcomplication

1717 1414

Tice J, Karliner L, Walsh J et al. Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures. The American Journal of Medicine. 2008;121:885-93.

Biliopancreatic diversionBiliopancreatic diversion

Restrictive and malabsorptive propertiesRestrictive and malabsorptive properties– Limited gastrectomyLimited gastrectomy– Roux-en-Y reconstructionRoux-en-Y reconstruction

Patient still allowed to eat a full mealPatient still allowed to eat a full meal

Results similar initially to gastric bypassResults similar initially to gastric bypass– Continued malabsorption increases 2Continued malabsorption increases 2ndnd year year

weight lossweight loss

Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.Matrusso A, Roslin M, Kurian M et al. Bariatric surgery: an overview of obesity surgery. 2006;119:1357-62.

Complications of Bariatric Complications of Bariatric SurgerySurgery

Unexpected Unexpected reoperationreoperation– Wound dehiscenceWound dehiscence– Foreign body removalForeign body removal– laparotomylaparotomy

Splenic Splenic – injuryinjury

HemorrhagicHemorrhagic– Intra-op hemorrhageIntra-op hemorrhage– Post-op hematomaPost-op hematoma– Blood transfusionBlood transfusion

AnastomoticAnastomotic– LeakLeak– Abdominal drainageAbdominal drainage

WoundWound– InfectionInfection– SeromaSeroma– dehiscencedehiscence

ObstructionObstruction– Small bowel Small bowel

obstructionobstruction

Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.

Short Bowel Syndrome Short Bowel Syndrome (SBS)(SBS)

Definition: intestinal remnant <180 Definition: intestinal remnant <180 cm AND malabsorptioncm AND malabsorption

Complications necessitate small Complications necessitate small bowel resectionbowel resection– Bowel obstructionBowel obstruction– Internal herniasInternal hernias– Mesenteric thrombosisMesenteric thrombosis

In a review of 265 pts with SBSIn a review of 265 pts with SBS– 15% due to bariatric surgery15% due to bariatric surgery

82% had Roux-en-Y gastric bypass82% had Roux-en-Y gastric bypassMcBride C, Petersen A, Sudan D. Short bowel syndrome following bariatric surgical procedures. American Journal of Surgery. 2006;192:828-32.

Outcomes in the Bariatric Outcomes in the Bariatric PatientPatient

Co-morbidities following Co-morbidities following TreatmentTreatment

TreatmentTreatment Absolute weight change Absolute weight change (kg)(kg)

SibutramineSibutramine -10.2-10.2

OrilstatOrilstat -7.6-7.6

BupropionBupropion -8.6-8.6

Gastric bypassGastric bypass -43.5-43.5

Gastric bandingGastric banding -28.6-28.6

Biliopancreatic Biliopancreatic diversiondiversion

-46.3-46.3

Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37.James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25.Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41.Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242.

Co-morbidities following Co-morbidities following TreatmentTreatment

TreatmentTreatment Systolic BP (mmHg)Systolic BP (mmHg)

SibutramineSibutramine 0.10.1

OrilstatOrilstat -0.8-0.8

BupropionBupropion -1.73-1.73

Gastric bypassGastric bypass ------

Gastric bandingGastric banding ------

Biliopancreatic Biliopancreatic diversiondiversion

------

Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37.James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25.Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41.Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242.

Co-morbidities following Co-morbidities following TreatmentTreatment

TreatmentTreatment Fasting glucose Fasting glucose (mg/dL)(mg/dL)

SibutramineSibutramine -0.8-0.8

OrilstatOrilstat 1.01.0

BupropionBupropion -2.71-2.71

Gastric bypassGastric bypass -3.4-3.4

Gastric bandingGastric banding -3.2-3.2

Biliopancreatic Biliopancreatic diversiondiversion

-5.79-5.79

Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37.James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25.Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41.Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242.

Co-morbidities following Co-morbidities following TreatmentTreatment

TreatmentTreatment LDL (mg/dL)LDL (mg/dL)

SibutramineSibutramine -0.8-0.8

OrilstatOrilstat -20-20

BupropionBupropion -2.95-2.95

Gastric bypassGastric bypass

Gastric bandingGastric banding

Biliopancreatic Biliopancreatic diversiondiversion

Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37.James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25.Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41.Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242.

Results from Bariatric Results from Bariatric SurgerySurgery

Co-morbidities resolve as weight Co-morbidities resolve as weight ↓↓

Hospitalization rate increasesHospitalization rate increases– Band adjustmentsBand adjustments– ComplicationsComplications

Complications existComplications exist– Nutritional deficienciesNutritional deficiencies– Medication absorption issuesMedication absorption issues– Surgical complicationsSurgical complications

Short bowel syndromeShort bowel syndrome

Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.

In the mean time . . . In the mean time . . .

Dosing Controversies in Dosing Controversies in ObesityObesity

Weight Weight – IBW vs. ABW vs. Adjusted body weightIBW vs. ABW vs. Adjusted body weight

DistributionDistribution– Lipophilic vs. hydrophilicLipophilic vs. hydrophilic– Protein boundProtein bound

ClearanceClearance AbsorptionAbsorption

– Following bariatric surgeryFollowing bariatric surgery

Erstad B. Which weight for weight-based dosage regimens in obese patients? AJHP. 2002;59:2105-10.

ConclusionsConclusions

Obesity is becoming more prevalentObesity is becoming more prevalent Genetic make-up may predispose pts to Genetic make-up may predispose pts to

obesityobesity Pharmacological agents + diet are Pharmacological agents + diet are

effective for overweight patientseffective for overweight patients Bariatric surgery is recommended for Bariatric surgery is recommended for

pts with BMI>35pts with BMI>35 Bariatric surgery is most effective Bariatric surgery is most effective

treatment for obesitytreatment for obesity