1. 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

2. Obesity Trends Among US Adults:
2002
No Data <10% %–14% %–19% %–24% ≥25%
No Data <10% %–14% %–19% %–24% ≥25%
2004
2000
No Data <10% %–14% %–19% ≥20
1998
No Data <10% %–14% %–19% ≥20
Obesity: BMI ≥30 kg/m2, or ~ ≥14 kg overweight for 163 cm person
DISCUSSION
Over the past 20 years, there has been a dramatic increase in obesity in the United States.
In 2004, 7 states had obesity prevalence rates of 15–19 percent; 33 states had rates of 20–24 percent; and 9 states had rates of more than 25 percent (no data for one state).
STUDY BACKGROUND
The data shown in these maps were collected through Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System (BRFSS).
Each year, state health departments use standard procedures to collect data through a series of monthly telephone interviews with US adults.
Prevalence estimates generated for the maps may vary slightly from those generated for the states by BRFSS as slightly different analytic methods are used.
Data from CDC. Behavioral Risk Factor Surveillance System.

3. Obesity Related Metabolic Disease
Low HDL
Insulin
Resistance
Metabolic
Syndrome
Obesity
Diabetes
High LDL
Hypertension

4. 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
DISCUSSION
Morbidity for a number of health conditions increases with increasing body weight.
A number of epidemiological studies also indicate that mortality begins to increase with increasing body weight.
NIH-NHLBI. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults

5. Overweight and Obesity Rates for Adults by Race/Ethnicity, 2005

6. Impact of Weight Loss on CV Risk Factors
HbA1c
Blood Pressure
Total Cholesterol
HDL Cholesterol
Triglycerides 1 1 2 2 3 3 3 3
Impact of weight loss on risk factors
Weight losses of 5%-10% have been shown to have a significant impact on several aspects of the metabolic syndrome, including well-recognized risk factors for cardiovascular disease and diabetes. For example:
Wing and colleagues at Brown University evaluated the effect of modest weight loss in 114 patients with type 2 diabetes. Those who lost 5% or more of their baseline weight showed statistically significant decreases in serum HbA1c levels [4].
The Trial of Antihypertensive Interventions and Management Study found that weight losses of 5% or more produced reductions in diastolic pressure that were equivalent to those produced by a single dose of antihypertensive medication [3].
Numerous studies have shown that weight losses of 5%-10% improve total cholesterol, LDL-to-HDL ratio, and the ratio of total-to-HDL cholesterol [1]. In one study, weight reduction of just 5.8% was associated with a 16% reduction in total cholesterol, an 18% increase in HDL cholesterol, and a 12% decrease in LDL cholesterol [1]. More recently, Ditschunheit and colleagues documented significant decreases in total cholesterol, triglycerides, and VLDL in obese patients with baseline hyperlipidemia who maintained a weight loss of 7.6% [2].
Blackburn G. Ob Res 1995;3(Suppl2):211S-216S.
Ditschunheit HH, et al. Lipoprotein responses to weight loss and weight maintenance in high-risk obese subjects. Eur J Clin Nutr 2002;56:
Mertens IL, Van Gaal LF. Overweight, obesity, and blood pressure: The effects of modest weight reduction. Ob Res 2000;8(3):
Wing RR, et al. Long-term effects of modest weight loss in Type 2 diabetic patients. Arch Intern Med 1987;147: 4
1. Wing RR et al. Arch Intern Med. 1987;147:
2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:
3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S.
4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:

7. Obesity Treatment Pyramid
Diet
Physical Activity
Lifestyle Modification
Pharmacotherapy
Surgery
Obesity treatment pyramid
The clinical approach to obesity can be viewed as a pyramid consisting of several levels of therapeutic options. All patients should be involved in an effort to change their lifestyle behaviors to decrease energy intake and increase physical activity. Lifestyle modification also should be a component of all other levels of therapy. Pharmacotherapy can be a useful adjunctive measure for properly selected patients. Bariatric surgery is an option for patients with severe obesity, who have not responded to less-intensive interventions. The number of obese patients who require a specific level of treatment decreases as one moves up the pyramid.

8. Guide for Selecting Obesity Treatment
BMI Category (kg/m2)
Treatment
>40
Diet, Exercise, Behavior Tx +
Pharmaco-therapy
With co- morbidities
Surgery
Guide for selecting obesity treatment
This table summarizes the guidelines for selecting treatment options for obesity [1]. Any effective treatment plan must consider the patient’s willingness to undergo therapy, his/her ability to comply with specific treatment approaches, access to skilled caregivers, and financial considerations. Lifestyle modification, which involves a program of appropriate diet, physical activity, and behavior therapy, should be considered for all patients with a body mass index (BMI) 25 kg/m2. Long-term pharmacotherapy should be considered in appropriate patients who were unable to achieve adequate weight loss after 6 months of lifestyle therapy and who have a BMI 30 kg/m2, or 27 kg/m2 with concomitant obesity-related disease. Bariatric surgery may be necessary in patients with severe obesity who failed to lose weight with non-surgical therapy. Eligible surgical candidates should have a BMI 40 kg/m2 or a BMI 35 kg/m2 and a concomitant serious obesity-related disease.
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub No
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub. No

9. 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
DISCUSSION
Weight loss via behavior modification (dieting and exercise) produces poor long-term results.
The few long-term weight loss drugs that are approved have limited efficacy and unwanted
side-effects.
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):
Moyers SV. J Am Diet Assoc 2005; 105:    

10. 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
1997
Diethylpropion
Tenulate
Short-term
1973
Phentermine
Adipex, lonamin
Phendimetrazine
Bontril, Prelu-2
III
1961
Benzphetamine
Didrex
1960
Drugs approved by FDA for treating obesity
This table lists the medications approved by the United States Food and Drug Administration (FDA) for treatment of obesity; only sibutramine (Meridia) and orlistat (Xenical) have been approved for long-term use. All the approved medications act as anorexiants, with the exception of orlistat, which blocks the absorption of dietary fat. Anorexiants increase satiation (level of fullness, which regulates the amount of food consumed during a meal) or satiety (level of fullness after a meal, which determines frequency of eating), or both. Methamphetamine is also approved by the FDA for short-term use, but it is a DEA schedule II drug and should be avoided because of its abuse potential. Three anorexiant medications have been removed from the marketplace because of increased risks of either valvular heart disease (fenfluramine and dexfenfluramine) [1] or hemorrhagic stroke (phenylpropanolamine) [2] associated with their use.
Khan MA, Herzog CA, St Peter JV, et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med 1998;339:
Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000;343:

11. Other Therapeutic Agent Comparison
Generic name
Orlistat
Sibutramine
Phentermine & Mazindol
Bupropion
Topiramate
Brand name
Xenical
Meridia
Generic
Wellbutrin
Topamax
Primary indication
Obesity
Depression
Epilepsy
Use
Long-term
Short-term
Off-label
Company
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
300, 400 mg QD
mg BID
DEA Schedule - 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
Suicidal thoughts
Paresthesia
Oily spotting
Incontinence
Dry mouth
Increased BP
Nervousness
Dizziness
Anxiety
Attention deficit
Memory loss
Palpitations
Sources: 1.) Padwal R et al. Cochrane Database Syst Rev. 2004;(3):CD004094; ) Package inserts ) Decision Resources

12. 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
Selected medications that can cause weight gain
Certain medications can cause weight gain and increase body fat, thereby making weight loss more difficult. This table presents a partial list of drugs and drug classes that contain medications associated with weight gain. These drugs differ in their propensity to increase body weight; some medications, such as the anticonvulsant valproic acid, can cause considerable weight gain of 15–20 kg, whereas other medications, such as the β-adrenergic receptor blocker propranolol, are associated with small and probably clinically insignificant weight gain. The mechanism responsible for medication-induced weight gain has not been carefully studied for most of these agents, but must be related to an increase in energy intake (e.g. antipsychotics and steroid hormones), a decrease in energy expenditure (e.g. β-adrenergic receptor blockers), a decrease in energy loss (e.g. decreased glucosuria from diabetes therapy), or a combination of these factors. Weight loss therapy can be facilitated by decreasing the dose or substituting the medication with another drug that has less weight gain potential, if possible.
Pijl H, Meinders AE. Bodyweight changes as an adverse effect of drug treatment. Drug Safety 1996;14:
SSRI=selective serotonin reuptake inhibitor

13. 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

14. Multi-Hormonal Control of Body Weight: Role Of Fat-, Gut-, And Islet-derived Signals
Amylin
GI tract
Adipose tissue
Pancreatic islets
Hypothalamus
Hindbrain
CCK
Adiponectin
Insulin
Leptin
OXM
Ghrelin
GLP-1
PYY3-36
GIP PP
Resistin
Visfatin
Vagal afferents
Adapted from Badman M.K. and Flier J.S. Science 2005; 307:

15. Obesity: Unmet Medical Need in Metabolic Disease Space
100-
80-
Pills
Future Pharmacotherapy
50-
Surgery
% of Patients 0- 30 25 20 15 10 5
Weight loss (%)
Current goal

16. Obesity Treatment Guidelines
The Practical Guide can be found at:
NHLBI web site:
NAASO web site:
Obesity treatment guidelines
The National Institutes of Health in conjunction with the National Heart, Lung, and Blood Institute (NHLBI) and the North American Association for the Study of Obesity have developed a Practical Guide for the identification, evaluation, and treatment of overweight and obesity in adults [1]. The Practical Guide is based on the clinical guidelines that were developed by the NHLBI’s Obesity Education Initiative, in cooperation with the National Institute of Diabetes and Digestive and Kidney Diseases, in June The Practical Guide contains useful information on diet therapy, physical activity, and behavior therapy and also provides guidance on the appropriate use of pharmacotherapy and surgery for healthcare practitioners.
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub No