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
Top Related