The Efficacy of Pharmaceutical Approaches to Weight Loss

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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

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Obesity Trends Among US Adults
Obesity BMI 30 kg/m2, or 14 kg overweight
for 163 cm person
Data from CDC. Behavioral Risk Factor
Surveillance System.
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Obesity Related Metabolic Disease
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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.
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Overweight and Obesity Rates for Adults by
Race/Ethnicity, 2005
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Impact of Weight Loss on CV Risk Factors
5Weight Loss 5-10Weight Loss
HbA1c
Blood Pressure
Total Cholesterol
HDL Cholesterol
Triglycerides
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1. Wing RR et al. Arch Intern Med.
19871471749-1753. 2. Mertens IL, Van Gaal LF.
Obes Res. 20008270-278. 3. Blackburn G. Obes
Res. 19953 (Suppl 2)211S-216S. 4. Ditschunheit
HH et al. Eur J Clin Nutr. 200256264-270.
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Obesity Treatment Pyramid
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Guide for Selecting Obesity Treatment
BMI Category (kg/m2)
Treatment 25-26.9 27-29.9 30-34.9 35-39.9 gt40
Diet, Exercise, Behavior Tx
Pharmaco-therapy With co-morbidities
Surgery With co-morbidities
The Practical Guide Identification, Evaluation,
and Treatment of Overweight and Obesity in
Adults. October 2000, NIH Pub. No.00-4084
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Current Obesity Treatments

• Non-pharmacological treatment (behavioral therapy
  including diet and exercise)
• Effective short-term (average weight loss lt5)
• 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
105948-959   
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Drugs Approved by FDA for Treating Obesity
Generic Name 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
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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
Use Long-term Long-term Short-term Off-label Off-label
Company Roche Abbott Varies GSK JJ
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
DEA Schedule - IV IV
Efficacy (1-y WL) 2.7 kg 4.3 kg no data 2 to 5 kg 5 to 8 kg
Side Effects Steatorrhea Insomnia Insomnia Suicidal thoughts Paresthesia
Oily spotting Incontinence Dry mouth Increased BP Nervousness Dizziness Anxiety Insomnia Attention deficit Memory loss
Palpitations Palpitations Depression
Sources 1.) Padwal R et al. Cochrane Database
Syst Rev. 2004(3)CD004094 2.) Package
inserts 3.) Decision Resources
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Selected Medications That Can Cause Weight Gain

• Psychotropic medications
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Specific SSRIs
• Atypical antipsychotics
• Lithium
• Specific anticonvulsants
• ?-adrenergic receptor blockers

• Diabetes medications
• Insulin
• Sulfonylureas
• Thiazolidinediones
• Highly active antiretroviral therapy
• Tamoxifen
• Steroid hormones
• Glucocorticoids
• Progestational steroids

SSRIselective serotonin reuptake inhibitor
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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

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Multi-Hormonal Control of Body WeightRole Of
Fat-, Gut-, And Islet-derived Signals
Adapted from Badman M.K. and Flier J.S. Science
2005 307 1909-1914.
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Obesity Unmet Medical Needin Metabolic Disease
Space
100-
80-
Pills
Surgery
50-
of Patients
0-
15
25
10
5
20
0
30
Weight loss ()
Current goal
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Obesity Treatment Guidelines
The Practical Guidecan be found at
NHLBI web sitewww.nhlbi.nih.gov NAASO web
sitewww.naaso.org