The Efficacy of Pharmaceutical
Approaches to Weight Loss
• Joseph Martinez, RPh, PDE, PPC
– former New Jersey State Medicaid Pharmacy
Director
– Medicaid 2004:
• 900,000 beneficiary lives covered
• Annual drug spend of $1.4 billion
Obesity Trends Among
US Adults:
1998
2000
2002
2004
Obesity: BMI ≥30 kg/m2, or ~ ≥14 kg overweight for 163 cm person
No Data
<10%
10%–14%
Data from CDC. Behavioral Risk Factor Surveillance System.
15%–19%
≥20
20%–24%
≥25%
Obesity Related Metabolic Disease
Hypertension
Obesity
Insulin
Resistance
Metabolic
Syndrome
Diabetes
High LDL
Low HDL
Health Risks of Obesity
Obesity is associated with an increased risk of:
• Morbidity
– Hypertension
– Dyslipidemia (high total cholesterol, high TG levels or
low HDL
– Coronary heart disease
– Type 2 diabetes
– Stroke
– Cancer (endometrial, breast and colon)
– Impairments in health-related quality of life and
psychosocial well-being
• Mortality
NIH-NHLBI. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. 1998.
Overweight and Obesity Rates for
Adults by Race/Ethnicity, 2005
0.7
0.6
0.5
White
Black
Hispanic
Asian Other
Other
0.4
0.3
0.2
0.1
0
United
States
New
Jersey
Impact of Weight Loss on CV Risk Factors
~5%
Weight Loss
5%-10%
Weight Loss
HbA1c
1
1
Blood Pressure
2
2
Total Cholesterol
3
3
HDL Cholesterol
3
3
Triglycerides
1. Wing RR et al. Arch Intern Med. 1987;147:1749-1753.
2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:270-278.
3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S.
4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:264-270.
4
Obesity Treatment Pyramid
Surgery
Pharmacotherapy
Lifestyle Modification
Diet
Physical Activity
Guide for Selecting Obesity Treatment
BMI Category (kg/m2)
Treatment
25-26.9
27-29.9
30-34.9
35-39.9
>40
Diet,
Exercise,
Behavior Tx
+
+
+
+
+
With comorbidities
+
+
+
With comorbidities
+
Pharmacotherapy
Surgery
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.
October 2000, NIH Pub. No.00-4084
Current Obesity Treatments
• Non-pharmacological treatment (behavioral therapy
including diet and exercise)
– Effective short-term (average weight loss <5%)
– Poor long-term compliance
– Weight loss is generally not sustained
• Pharmacological treatment
– Only two drugs, sibutramine and orlistat, presently approved
for long-term use
– Modestly effective (average weight loss 5-10% compared to
placebo)
– Side effects include increased heart rate and blood pressure,
abdominal pain, incontinence, and flatulence
Yanovsky SZ, et al. New England J Med 2002; 346(8):591-602.
Moyers SV. J Am Diet Assoc 2005; 105:948-959
Drugs Approved by FDA for
Treating Obesity
Trade
Names
DEA
Schedule
Approved
Use
Year
Approved
Orlistat
Xenical
None
Long-term
1999
Sibutramine
Meridia
IV
Long-term
1997
Diethylpropion
Tenulate
IV
Short-term
1973
Phentermine
Adipex,
lonamin
IV
Short-term
1973
Phendimetrazine
Bontril,
Prelu-2
III
Short-term
1961
Benzphetamine
Didrex
III
Short-term
1960
Generic Name
Other Therapeutic Agent Comparison
Generic name
Orlistat
Sibutramine
Phentermine &
Mazindol
Bupropion
Topiramate
Brand name
Xenical
Meridia
Generic
Wellbutrin
Topamax
Primary indication
Obesity
Obesity
Obesity
Depression
Epilepsy
Long-term
Long-term
Short-term
Off-label
Off-label
Roche
Abbott
Varies
GSK
J&J
MOA
GI lipase
inhibitor
CNS monoamine
reuptake inhibitor
Noradrenergic
GABA agonist
Dopamine agonist
Dosing
120 mg TID
5-15 mg QD
Varies
300, 400 mg QD
96-384 mg BID
-
IV
IV
– 2.7 kg
– 4.3 kg
no data
– 2 to 5 kg
– 5 to 8 kg
Steatorrhea
Insomnia
Insomnia
Suicidal thoughts
Paresthesia
Oily spotting
Incontinence
Dry mouth
Increased BP
Nervousness
Dizziness
Anxiety
Insomnia
Attention deficit
Memory loss
Palpitations
Palpitations
Depression
Use
Company
DEA Schedule
Efficacy (1-y WL)
Side Effects
Sources: 1.) Padwal R et al. Cochrane Database Syst Rev. 2004;(3):CD004094;
2.) Package inserts
3.) Decision Resources
Selected Medications That Can
Cause Weight Gain
• Psychotropic medications

Diabetes medications
– Insulin
– Sulfonylureas
– Thiazolidinediones

Highly active antiretroviral
therapy
– Lithium

Tamoxifen
– Specific anticonvulsants

Steroid hormones
– Glucocorticoids
– Progestational steroids
– Tricyclic antidepressants
– Monoamine oxidase
inhibitors
– Specific SSRIs
– Atypical antipsychotics
• -adrenergic receptor blockers
SSRI=selective serotonin reuptake inhibitor
Obesity in the US: Disease Burden
• Enormous disease burden:
• Public health:
• 65% (~127M) US adults are overweight (BMI  25 kg/m2)
• 31% (~60M) are obese (BMI  30 kg/m2)
• 5% (~9M) are severely obese (BMI  40 kg/m2)
• Medical impact: considerable increase in morbidity, disability, and mortality
• 2nd-ranked preventable cause of death (~365,000/y)
• Economic impact: ~$127 billion/y (~5% of every health care $)
• Increasingly acknowledged as a serious, treatment-requiring condition
•
•
•
•
•
Medical profession
Public policy makers
Managed care
Federal regulators
Pharmaceutical industry
Multi-Hormonal Control of Body Weight:
Role Of Fat-, Gut-, And Islet-derived Signals
Vagal afferents
Hypothalamus
GI tract
Adipose tissue
Ghrelin
Hindbrain
CCK
Leptin
PYY3-36
Insulin
Amylin
GLP-1
Resistin
Visfatin
OXM
Adiponectin
Adapted from Badman M.K. and Flier J.S. Science 2005; 307: 1909-1914.
GIP
PP
Pancreatic
Amylin islets
Obesity: Unmet Medical Need
in Metabolic Disease Space
100-
80-
50-
Surgery
Future
Pills
Pharmacotherapy
030
25
20
15
Weight loss (%)
10
5
0
Current goal
Obesity Treatment Guidelines
The Practical Guide
can be found at:
NHLBI web site:
www.nhlbi.nih.gov
NAASO web site:
www.naaso.org