Transcript Placebo - Medscape

Obesity as a CNS Disorder:
Targeting the Neuronal Circuitry
of Weight Loss
Robert F. Kushner, MD, MS
Professor of Medicine
Feinberg School of Medicine
Northwestern University
Clinical Director
Northwestern Comprehensive Center on Obesity
Chicago, Illinois
Learning Objectives
Upon completion of this activity, you should be able to:
• Differentiate the mechanisms of action of the new
targeted pharmacotherapies for obesity in
development from the current approaches to obesity
management
• Evaluate the efficacy, safety, and tolerability of
emerging antiobesity therapies, and where they may
fit into the current obesity algorithms
What percentage of your patients
are either overweight or obese?
 < 25%
 25%-50%
 51%-75%
 > 75%
 I don’t see patients currently
Systems Review: Cardiovascular, Respiratory,
Neurologic, Endocrine, and Psychological
• Cardiovascular






Hypertension
Congestive heart failure
Cor pulmonale
Varicose veins
Pulmonary embolism
Coronary artery disease
• Neurologic



Respiratory





Endocrine
Stroke
Idiopathic intracranial
hypertension
Meralgia paresthetica

Depression
Body image disturbance
Low self-esteem
Impaired quality of life




Psychological




Dyspnea
Obstructive sleep apnea
Hypoventilation syndrome
Pickwickian syndrome
Asthma
Metabolic syndrome
Type 2 diabetes mellitus
Dyslipidemia
Polycystic ovary
syndrome/androgenicity
Amenorrhea/infertility/menstrual
disorders
Systems Review: Musculoskeletal,
Integumentary, GI, and Genitourinary
• Musculoskeletal





Hyperuricemia and gout
Immobility
Osteoarthritis (knees/hips)
Low back pain
Carpal tunnel syndrome
• Integumentary





Striae distensae (stretch marks)
Stasis pigmentation of legs
Cellulitis
Acanthosis nigricans/skin tags
Intertrigo, carbuncles
• Gastrointestinal





GERD
Nonalcoholic fatty liver disease
Cholelithiasis
Hernias
Colon cancer
• Genitourinary






Urinary stress incontinence
Obesity-related glomerulopathy
Kidney stones
Hypogonadism
Breast and uterine cancer
Pregnancy complications
Age-Adjusted Relative Risk
Relationship Between BMI and
Risk for Type 2 Diabetes Mellitus
93.2
100
Men
Women
75
54.0
40.3
50
42.1
27.6
25
1.0
2.9
1.0
4.3
1.0
5.0
1.5
23-23.9
24-24.9
8.1
2.2
21.3
15.8
6.7
11.6
4.4
0
< 22
< 23
25-26.9
27-28.9
29-30.9
Body Mass Index (BMI; kg/m2)
Chan J, et al. Diabetes Care. 1994;17:961-969.
Colditz G, et al. Ann Intern Med. 1995;122:481-486.
31-32.9
33-34.9
35+
Association of Waist-to-Hip Ratio
Within BMI Categories With MI
Results expressed by waist-to-height ratio quintiles and BMI categories
Yusuf S, et al. Lancet. 2005;366:1640-1649.
Relative Risk for Death From Cardiovascular
Disease, Cancer, and All Other Causes
Cardiovascular disease
Cancer
All other causes
Women
3.2
3.0
2.8
2.6
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
Relative Risk for Death
Relative Risk for Death
Men
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
Body Mass Index
The reference category consisted of participants with BMIs of 23.5-24.9 kg/m2.
Calle EE, et al. N Engl J Med. 1999;341:1097-1105.
BMI and All-Cause Mortality
Hazard ratio (HR) per 5 kg/m2 higher BMI. HR less than 1 if BMI is inversely
associated with risk . All analyses exclude the first 5 years of follow-up and adjust
for study and age at risk (in 5-year groups). The overall and age-specific analyses
also adjust for sex, and the all-participant analyses also adjust for baseline smoking
status.
Prospective Studies Collaboration. Lancet. 2009;373:1083-1096.
Effect of BMI on Lifespan
Prospective Studies Collaboration. Lancet. 2009;373:1083-1096.
All Healthcare Professionals Play a Role
• Screening for Obesity in Adults. The US Preventive
Services Task Force recommends that clinicians
screen all adult patients for obesity and offer
intensive counseling and behavioral interventions to
promote sustained weight loss for obese adults
(Grade B recommendation)
U.S. Preventive Services Task Force. Ann Intern Med. 2003;139:930-932.
All Healthcare Professionals Play a Role
• Periodically monitor for change in weight by noting
weight trajectory over time
• Provide dietary, physical activity, and lifestyle
counseling to “at-risk” patients, and consider
pharmacologic and surgical treatment when indicated
U.S. Preventive Services Task Force. Ann Intern Med. 2003;139:930-932.
I understand the role of the central nervous system in
weight regulation.
 Strongly agree
 Agree
 Disagree
 Strongly disagree
 Neither agree nor disagree
Mechanisms of Food Intake
Family & Social
Influences
Sensory Factors:
•Taste
•Smell
•Texture
•Sight
Effects of:
•Variety
•Sensory-specific satiety
•Palatability
•Food concentration
•Ready availability
Cognitive Factors:
•Conscious rational control
•Beliefs about the food
•Advertising
Brain Mechanisms:
•Modulate sensory
factors by satiety signals
to produce reward value
and appetite
Satiety/Hunger Signals:
•Fat cell hormones
•Gut hormones
•Gastric distention
Adapted from: Rolls ET. Obes Rev. 2007;8(suppl1):67-72.
Eating
Model Summarizing Different Levels of
Control Over Appetite Regulation
Woods SC, et al. J Clin Endocrinol Metab. 2008;93(suppl1):S37-S50.
Gut Peptides That Regulate Appetite
Murphy KG, Bloom SR. Nature. 2006;444:854-859.
Gut Peptides That Regulate Appetite
Murphy KG, Bloom SR. Nature. 2006;444:854-859.
The Importance of the Hypothalamus
in Appetite Regulation
•Injury or lesions in the hypothalamus may
result in a pattern of weight gain that is
characterized as abrupt in onset and rapidly
accelerating = hypothalamic obesity
•Causes include:
•
•
•
•
Craniopharyngioma
Head trauma
Sarcoidosis
Aneurysm
•
•
•
•
Meningioma
Metastasis
Surgery
Radiation
A Case of Hypothalamic Obesity
Neuroregulation of Energy Balance
5-HT2c receptors
Obesity Treatment Pyramid
Surgery
BMI
Pharmacotherapy
Lifestyle Modification
Diet
Physical Activity
How confident are you that your understanding
of emerging pharmacotherapies for treatment of
obesity is up-to-date?
 Very confident
 Somewhat confident
 Not very confident
Emerging Antiobesity Drugs
and Drug Combinations
•Lorcaserin, a selective 5-HT2C receptor agonist
•Naltrexone + bupropion
•Phentermine and topiramate
Lorcaserin
Lorcaserin: selective 5-HT2C receptor agonist
designed to promote weight loss
 5-HT2C receptor activation of proopiomelanocortin (POMC)
neurons results in α-MSH activation of melanocortin-4
receptors
 Serotonin receptor as a pharmacologic target for weight
loss was validated by fenfluramine
 Fenfluramine in combination with phentermine (Fen-Phen)
was highly efficacious for weight loss
 Safety concerns led to withdrawal: Fenfluramine activation
of 5-HT2B receptor was linked to cardiac valvular disease
Heisler LK, et al. Science. 2002;297:609-611.
Behavioral Modification and Lorcaserin for
Obesity and Overweight Management (BLOOM)
Study Week
0
Weight change (kg)
8
16
24
-2
32
40
48
64
72
80
88
96 104
ITT/LOCF
-4
Per
Protocol
ITT/LOCF
-6
-8
-10
N = 344
N = 140
N = 308
PBO/PBO
Lorc/PBO
Lorc/Lorc
Lorcaserin (Lorc) vs placebo (PBO): P < .0001 at all timepoints
Lorc/Lorc vs Lorc/PBO: P < .0001 at all year 2 timepoints
Smith SR, et al. ADA 2009. Late-Breaking Abstract 96.
Echocardiographic Monitoring and Endpoints
• Echoes were performed every 6 months
• Heart valve insufficiency (or regurgitation) is rated as follows:
• Aortic: absent; trace; mild; moderate; severe
• Mitral: absent; trace; mild; moderate; severe
• Tricuspid: absent; trace; mild; moderate; severe
• Pulmonic: absent; present
• The US Food and Drug Administration (FDA) defines significant
valvular disease as MILD or greater aortic regurgitation, or
MODERATE or greater mitral regurgitation
• Main endpoint: proportion of patients who develop “FDA
valvulopathy”
• Secondary endpoints: shift analyses of individual heart valve
regurgitant scores
CDC. MMWR Morb Mortal Wkly Rep. 1997;46:1061-1066.
Lorcaserin Did Not Increase the Rate
of FDA Valvulopathy
Treatment
Lorcaserin 10 mg BID
Placebo
N
n (%)
Week 52
1278
1194
34 (2.66%)
28 (2.35%)
P
.70a
Week 104
Lorcaserin/lorcaserin
Lorcaserin/placebo
Placebo/placebo
500
258
627
13 (2.6%)
5 (1.9%)
17 (2.7%)
.99a
N = number of evaluable echo pairs; n = number (%) with FDA valvulopathy
aVs
placebo with Fisher’s exact test
Smith SR, et al. ADA 2009. Late-Breaking Abstract 96.
Lorcaserin: Adverse Events Reported by 5%
or More in Any Group in Year 1
N (%)
Lorcaserin
(N = 1593)
Placebo
(N = 1584)
Headache
287 (18.0)
175 (11.0)
Dizziness
130 (8.2)
60 (3.8)
Nausea
119 (7.5)
85 (5.4)
Constipation
106 (6.7)
64 (4.0)
Fatigue
95 (6.0)
48 (3.0)
Dry mouth
83 (5.2)
37 (2.3)
Smith SR, et al. ADA 2009. Late-Breaking Abstract 96.
28
Naltrexone and Bupropion Rationally
Designed Around MOA to Initiate and
Sustain Weight Loss
 Obesity: complex, multiple
pathways to defend body weight
 Preclinical/clinical evidence for
drug synergy
Weight loss
α-MSH
 Naltrexone/bupropion synergistic
Bupropion
increase in POMC activity
 Synergistic decrease in food
intake and body weight
MC4R = melanocortin-4 receptor; MOA = mechanism of action;
MSH = melanocyte-stimulating hormone; POMC = proopiomelanocortin
Greenway FL, et al. Obesity. 2009;17:30-39.
Naltrexone
β-endorphin
COR-I, II: Body Weight, Percentage of
Change From Baseline
COR-I
Observed
Change from baseline (%)
0
ITT-LOCF
-2
-1.9%
-4
-1.3%
-5.0%*
-6
Placebo (N=456)
NB32 (N=471)
NB16 (N=471)
-6.8%*
-6.1%*
-8
COR-II
NB32 (N=702)
Observed#
0
Change from baseline (%)
Placebo (N=511)
ITT-LOCF
-1.4% -1.2%
-2
-4
-6
-6.4%*
-8
-8.1%*
-8.2%*
-10
0
8
16
24
32
40
48
56
56
Week
Completers: Placebo (N = 290): -1.8% , NB16 (N = 284): -6.7%*
NB32 (N = 296): -8.1%*
-10
0
8
16
24
32
40
48
56
56
Week
Completers: Placebo (N = 267): -1.4%
NB32 (N = 434): -8.2%*
NB = naltrexone/bupropion. #COR-II: NB observed data are NB32/NB48 pooled (N = 825); no differences were observed for patients
rerandomized to NB32 vs NB48. LS mean ± SE; *P < .001 vs placebo at all timepoints. COR-II: week 56 ITT-LOCF data from patients
rerandomized to NB32 are double weighted to account for the prespecified exclusion of patients rerandomized to NB48. ITT-LOCF: patients
with a baseline and ≥ 1 postbaseline weight measurement while on study drug.
Press release. October 27, 2009. Available at:
http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1346886&highlight Accessed April 29, 2010.
COR-I, II: Categoric Weight Loss at Week
56, ITT-LOCF
80
Placebo (N=511)
COR-I
56.3%
ITT-LOCF
60
Percentage of patients
subjects
Percentage of patients
subjects
ITT-LOCF
*
48.0%
40
*
24.6%
20 16.4%
*
60
*
50.5%
40
*
28.3%
20 17.1%
5.7%
2.0%
5%
*
13.5%
11.9%
7.4%
0
NB32 (N=702)
Placebo (N=456)
80 COR-II
*
NB32 (N=471)
10%
15%
0
5%
10%
2.4%
15%
Data are for the ITT-LOCF population. *P < .001 vs placebo . COR-II: week 56 data from patients rerandomized to NB32 are double weighted to
account for the prespecified exclusion of patients rerandomized to NB48. ITT-LOCF: patients with a baseline and ≥ 1 postbaseline weight
measurement while on study drug.
Press release. October 27, 2009. Available at:
http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irolnewsArticle&ID=1346886&highlight
Accessed April 29, 2010.
COR-I: Improvements in Control of Eating,
ITT-LOCF
COR-I
Placebo
(N = 511)
NB32
(N = 471)
How difficult has it been to
control your eating?
How difficult has it been to
resist any food cravings?
How often have you eaten in
response to food cravings?
Less
More
Change from baseline to week 56 endpoint for eating/craving-related items showing differences (P < .05) at weeks 8,
16, 28, and 56 in both COR-I and COR-II; responses reflect experiences during the 7 days prior to answering the
questionnaire; ITT-LOCF: patients with a baseline and ≥ 1 postbaseline weight measurement while on study drug. Data
are LS mean ± SE; *P < .05 vs placebo; the COEQ consists of 21 questions with responses given using a 100-mm visual
analogue scale. COR-II: week 56 data from patients rerandomized to NB32 are double weighted to account for the
prespecified exclusion of patients rerandomized to NB48.
Press release. October 27, 2009. Available at:
http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irolnewsArticle&ID=1346886&highlight
Accessed April 29, 2010.
COR-II: Improvements in Control of
Eating, ITT-LOCF
COR-II
Placebo
(N = 456)
NB32
(N = 702)
How difficult has it been to
control your eating?
How difficult has it been to
resist any food cravings?
How often have you had
food cravings?
Less
More
Change from baseline to week 56 endpoint for eating/craving-related items showing differences (P < .05) at weeks 8,
16, 28, and 56 in both COR-I and COR-II; responses reflect experiences during the 7 days prior to answering the
questionnaire; ITT-LOCF: patients with a baseline and ≥ 1 postbaseline weight measurement while on study drug. Data
are LS mean ± SE; *P < .05 vs placebo; the COEQ consists of 21 questions with responses given using a 100-mm visual
analogue scale. COR-II: week 56 data from patients rerandomized to NB32 are double weighted to account for the
prespecified exclusion of patients rerandomized to NB48.
Press release. October 27, 2009. Available at:
http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irolnewsArticle&ID=1346886&highlight
Accessed April 29, 2010.
COR-I, II: Most Common
Treatment-Emergent Adverse
Events (TEAE)
Placebo
NB16
COR-I
COR-II
N=569
N=569
NB32
N=573
Nausea
5.3%
27.2%*
29.8%*
6.9%
29.2%*
Headache
9.3%
16.0%*
13.8%*
8.7%
17.5%*
Constipation
5.6%
15.8%*
15.7%*
7.1%
19.1%*
Dizziness
2.6%
7.7%*
9.4%*
3.7%
6.9%*
Vomiting
2.5%
6.3%*
9.8%*
2.0%
8.5%*
Dry mouth
1.9%
7.4%*
7.5%*
2.6%
9.1%*
9.8%
21.4%*
19.5%*
13.8%
24.3%*
Nausea
0.4%
4.6%*
6.3%*
0.2%
6.0%*
Dizziness
0.5%
2.3%*
1.2%
0.2%
1.0%
Headache
0.7%
1.6%
0.9%
0.8%
2.6%*
Vomiting
0.2%
0.7%
0.9%
0%
0.8%
Insomnia
0.2%
0.7%
0.7%
1.0%
0.8%
Patients discontinuing due to a TEAE
Placebo
N=492
NB32/48
N=992
TEAEs > 5% in any NB group and 2x the incidence in the respective placebo group. Top 5 TEAEs leading to discontinuation
in NB groups. Data are for the safety analysis set: patients taking ≥ 1 tablet of study drug and with ≥ 1 investigator
contact/assessment at any time after the start of study treatment. *P < .05 vs placebo
Press release. October 27, 2009. Available at:
http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irolnewsArticle&ID=1346886&highlight
Accessed April 29, 2010.
COR-I, II: Incidence of Nausea by Week
and Intensity
Placebo
N = 1061
100
NB
N = 2134
100
titration
period
15
Mild
Moderate
Severe
10
5
0
4
8 12 16 20 24 28 32 36 40 44 48 52 56
Incidence of nausea (%)
Incidence of nausea (%)
titration
period
15
Mild
Moderate
Severe
10
5
0
4
8 12 16 20 24 28 32 36 40 44 48 52 56
Nausea events are shown during
week of onset only. If a patient had multiple-event onsets during
the same week,
Week
Week
only the most severe event is shown. Safety analysis set: patients taking ≥ 1 tablet of study drug and with ≥ 1
investigator contact/assessment at any time after the start of study treatment. Placebo data are combined for COR-I
and COR-II. All NB data are combined for COR-I and COR-II (NB16, NB32, NB48).
Press release. October 27, 2009. Available at:
http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irolnewsArticle&ID=1346886&highlight
Accessed April 29, 2010.
Potential Activities of Topiramate
Involved in Energy Balance
Activity







Significance to Body Weight Loss
Inhibits activity of glutamate at
AMPA/kainate receptors
Inhibits activation of L-type
voltage-dependent Ca++ channels
Inhibits carbonic anhydrase
(CA-II, CA-IV)
Modulates lipoprotein lipase
activity
Stimulates thermogenesis and
energy expenditure (some models)
Downregulation of corticotropinreleasing hormone, glucocorticoids
(GC), and GC receptors (depends
on model)
Other preliminary data
Reduces body weight (?)
Reduces body weight (?)
Reduces body weight (?)
Reduces fat deposition
and triglycerides
Reduces body weight
Reduces body weight, other
effects on energy metabolism
Effects on energy metabolism
Topiramate in Obesity: Percentage of Body
Weight Change From Baseline to Week 24
Weeks
0
2
4
6
8
10
12
14
16
18
20
22
24
0
Weight Change (%)
-2
Placebo (n=48)
-4
64 mg/d TPM (n=57)
-6
96 mg/d TPM (n=49)
-8
192 mg/d TPM (n=50)
384 mg/d TPM (n=44)
-10
P < .05 from week 4
TPM = topiramate
Bray G, et al. Obes Res. 2003;11:722-733.
Proprietary Investigational Treatment
for Obesity
• Once-daily, oral, controlled-release formulation of lowdose phentermine and topiramate
• Specifically designed to affect normal eating patterns
over 24 hours -- simultaneously addressing appetite,
satiety, and cravings
23 46
92
Maximum
Approved
Doses
Topiramate
0
50
100
150
200
250
300
350
400 mg
Phentermine
0
3.75
Low
5
7.5
Mid
10
15
20
25
Full
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=407933
Accessed April 27, 2010.
30 mg
(free base)
EQUIP: Weight Loss Over Time
(Completer Population)
Mean % Weight Loss
Placebo
-2.5%, 6 lb
Low (23T, 3.75P)
-7.0%, 18 lb
Full (92T, 15P)
-14.7%, 37 lb
Data from patients who completed 56 weeks on treatment
Weeks
Patients
Placebo
Low
Full
Completers (% of randomized)
241 (47%)
138 (57%)*
301 (59%)*
*Statistically
greater number of patients completing study on combination drug vs placebo, P < .0001
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
CONQUER: Weight Loss Over Time
(Completer Population)
Mean % Weight Loss
Placebo
-2.4%, 6 lb
Mid (46T, 7.5P)
-10.5%, 24 lb
Full (92T, 15P)
-13.2%, 30 lb
Data from patients who completed 56 weeks on treatment
Weeks
Patients
Placebo
Completers (% of randomized)
*Statistically
564 (57%)
Mid
344 (69%)*
Full
634 (64%)*
greater number of patients completing study on combination drug vs placebo, P < .0001
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
EQUIP: Significant Categoric Weight Loss With
Phentermine and Topiramate (Low and Full Dose)
Completers
Weight Loss
15%
**P < .0001 vs placebo
*P = .026 vs placebo
10%
5%
0
10
20
30 40 50
% of Patients
Placebo
Qnexa
LowLow
60
70
80
% of Patients with:
• ≥ 15% wt loss
Placebo 5%
Low 11%*
Full 43%**
• ≥ 10% wt loss
Placebo 12%
Low 27%**
Full 60%**
• ≥ 5% wt loss
Placebo 26%
Low 59%**
Full 84%**
90
Qnexa
FullFull
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
CONQUER: Significant Categoric Weight Loss
With Phentermine and Topiramate (Mid and Full
% of Patients with:
Dose)
Completers
**P < .0001 vs placebo
Weight Loss
15%
• ≥ 15% wt loss
Placebo 4%
Mid 26%**
Full 39%**
• ≥ 10% wt loss
Placebo 10%
Mid 49%**
Full 64%**
10%
5%
0
10
20
30
40
50
60
70
80
• ≥ 5% wt loss
Placebo 26%
Mid 75%**
90 Full 85%**
% of Patients
Placebo
Placebo
Qnexa
Mid
Low
FullFull
Qnexa
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
EQUIP & CONQUER: TEAEs > 5%
EQUIP (N = 1264)
% of Patients
(N = 3749)
CONQUER (N = 2485)
Placebo
Low
Full
Placebo
Mid
Full
Dry mouth
3.7
6.7
17.0
2.4
13.5
20.8
Tingling
1.9
4.2
18.8
2.0
13.7
20.5
Constipation
6.8
7.9
14.1
5.9
15.1
17.4
Altered taste
1.0
1.3
8.4
1.1
7.4
10.4
Insomnia
4.9
5.0
7.8
4.7
5.8
10.3
Dizziness
4.1
2.9
5.7
3.1
7.2
10.0
Nausea
4.7
5.8
7.2
4.2
3.6
6.8
Blurred vision
3.1
6.3
4.5
3.6
4.0
6.0
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
EQUIP & CONQUER: Discontinuation Rate
Due to AEs in All Doses Studied
Number of patients
Discontinuation due to AEs
Blurred vision
Headache
Insomnia
Depression
Tingling
Irritability
Anxiety
Dizziness
Placebo
Low
Mid
Full
1508
9%
241
12%
498
12%
1507
18%
0.5%
0.7%
0.4%
0.2%
0.0%
0.1%
0.3%
0.2%
2.1%
1.7%
0.0%
0.0%
0.4%
0.8%
0.0%
0.4%
0.8%
0.2%
0.4%
0.8%
1.0%
0.8%
0.2%
1.2%
0.7%
0.9%
1.7%
1.4%
1.2%
1.2%
1.1%
0.8%
Includes adverse events (AEs) by dose for EQUIP & CONQUER, which lead to discontinuation
in > 1% of patients
Press release. Sept 9, 2009. Available at: http://ir.vivus.com/releasedetail.cfm?ReleaseID=420114
Accessed April 27, 2010.
A Guide to Selecting Obesity Treatment
BMI Category (kg/m2)
Treatment
Diet, physical
activity, and
behavior therapy
25-26.9
27-29.9
30-34.9
35-39.9
 40
With
comorbidity
+
-
+
-
+
-
+
-
With
comorbidity
+
-
+
-
+
-
With
comorbidity
+
-
Pharmacotherapy
Surgery
NIH, et al. NIH. 2000;00-4804:1-84.
Summary
• Appetite control and energy expenditure are
regulated by peripheral and central signaling
mechanisms
• Newer antiobesity agents target these processes
• Due to the complexity of the hypothalamic circuitry,
combined drug therapy is likely to be more effective
than monotherapy for weight control
• Antiobesity medications are anticipated to have a
more significant role in the treatment of patients with
obesity
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