Hot Topics in Obesity Treatment

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Overweight or obese Overweight Obese(BMI 25.0) (BMI 25.0-29.9) (BMI 30.0)

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NHANES† 1999-2000(n=3601)

NHANES III1988-1994(n=14,468)

NHANES=National Health and Nutrition Examination Survey.*Age-adjusted by the direct method to the year 2000; US Bureau of the Census estimates using the age groups 20-34, 35-44, 45-54, 55-64, and 65-74 years†Flegal KM et al. JAMA. 2002;288:1723-1727.

Prevalence of Overweight and Obesity Among US Adults

Binge Eating

• Could there be a survival advantage to being able to binge or eat more in an environment with limited food?

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Binge and MC4R Gene

• Two articles in the NEJM March 2003

– Branson: 5.1% of obese had MC4R gene mutations

– Farooqi: 5.8 % of obese had MC4R gene mutations

• All mutation carriers reported binge eating

Binge Eating

• 469 morbid obese Caucasian patients

• 79% female

• Found 24 pts (5.1%) with a mutation of the MC4R – Basically a defective receptor

• All 24 of these pts (100%) had binge eating

• Only 14% of matched controls had binging

NEJM 348:12, 2003.

Binge Eating

• 500 morbid obese children

• Found 29 pts (5.8%) with a mutation of the MC4R – Basically a defective receptor

• All 29 of these patients had “hyperphagia”

• Compared to unaffected siblings they ate three times as much food at a single meal– Meal size corrected for lean body mass

NEJM 348:12, 2003.

Homozygous Mutation in Melanocortin-4 Receptor Gene

Farooqi IS et al. N Engl J Med. 2003;348:1085-1095.

SiblingWithMutation

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MC4R Mutations

• Mutations carriers were:– Severely obese

– Increased lean mass

– Increased linear growth

– Severe hyper-insulinemia

• Homozygotes were more severely effected than heterozygotes

Binge Eating Disorder

• Eating an amount of food that is definitely larger than most people would eat in similar circumstances during a similar period of time (eg, 2x a normal portion in 2 hours)

• A sense of lack of control during the episodes– Sense of inability to stop or control eating

• Marked distress about the binge eating– Women yes, men often not

• Binge eating is a provisional DSM code at this time

Definition of a Binge Episode

Secondary Binge Criteria

• Eat alone (closet eating)

• Eat when not hungry

• Eat fast

• Eats until uncomfortably full

• Feeling of guilt or un-happiness after eating

• Loose criteria different for men and women

Questions for the Clinician to Ask Patients Who Might Have

Binge Eating Disorder

• Do you ever have episodes of eating where you feel out of control or that you just could not stop yourself?

• Do you ever eat large portions of food that would clearly be larger portions that other persons might eat in a similar circumstance?

Diagnostic Criteria for Bulimia Nervosa (BN)

• Recurrent episodes of binge eating with loss of control

• Recurrent inappropriate compensatory behavior to prevent weight gain

• Binge eating and inappropriate compensatory behavior both occur, on average, at least twice a week for 3 months

• Self-evaluation is unduly influenced by body shape and weight

Prevalence of BED in Community Samples

• BED is found in ~ 2% to 3% of adults

– About half are obese

Bruce B, Agras WS. Int J Eat Disord. 1992;12:365-373. Spitzer RL et al. Int J Eat Disord. 1992;11:191-203.

Prevalence of BED in Clinical Samples

• BED in obese treatment seekers– ~ 7.6% to 18.8% (rigorously defined)

– ~ 20% to 40% (broadly defined)

• BED in Overeaters Anonymous: ~ 70%

• BED in bariatric surgery seekers: ~ 25% to 50%

Stunkard AJ. In: Handbook of Obesity Treatment. 2002. Wadden TA et al. Surg Clin N Am. 2001;81:1001-1014. Williamson DA, Martin CK. Eat Weight Disord. 1999;4:103-114.

Yanovski SZ, et al. Am J Psychiatry. 1993; 150:1472-1479.

BED and Depression

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Telch CF et al. Int J Eat Disord. 1988;7:115-119.

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Fluoxetine Bulimia Nervosa Collaborative Study Group. Arch Gen Psychiatry. 1992;49:139-147.

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Arnold LM et al. J Clin Psychiatry. 2002;63:1023-1028.

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• 4-week placebo run-in; 6-month double-blind treatment– Placebo run-in n = 549– Randomized n = 304– Completed n = 189

• Baseline values determined after placebo run-in

• Outcome measures:– Binge frequency and weight

• A significant difference from placebo was achieved for both outcomes

Wilfley DE et al. Presented at: the Eating Disorders Research Society Annual Meeting; Charleston, South Carolina; November 20-22, 2002.

Wilfley DE et al. Presented at: the Eating Disorders Research Society Annual Meeting; Charleston, South Carolina; November 20-22, 2002.

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Pharmacologic and Surgical Management of Obesity

in Primary Care: A Clinical Practice Guideline

from the ACP

Ann Intern Med 2005;142:525-531.

Medications Used for Weight Loss

• Phentermine*• Diethylpropion*• Sibutramine#

• Orlistat#

* Approved by the FDA for short term weight loss

# Approved by the FDA for weight loss and weight maintenance

“Off-label” Use of Medications for Weight Loss

• Bupropion

• Fluoxetine

• Sertraline

• Topiramate

• Zonisamide

Coverage of Weight Loss Medications

• Typically not covered as a general rule

• Although see 30% to 40% coverage

• Typically covered medical conditions that get coverage of weight loss medications– Morbid obesity:

− With the threat of bariatric surgery

– Diabetes

– Patients with BMI of ≥ 35 with co-morbid condition

– Metabolic syndrome

Paperwork: Billing Codes

• Very rarely covered by health insurances– Obesity – 278.00

• Usually paid billing codes – Morbid obesity – 278.01

– Dysmetabolic Syndrome – 277.7

– Impaired fasting glucose – 790.21

– Impaired GTT – 790.22

ACP Guidelines

• 5 recommendations based on the evidence report and accompanying background papers developed by the Southern California Evidence-Based Practice Center

• The ACP recommends all clinicians refer to these guidelines as part of an overall strategy for managing overweight and obese patients

• Overall strategy should always include appropriate diet and exercise

• Target audience is patients with BMIs of above 30

ACP GuidelinesRecommendation #1

• Clinicians should counsel all patients with a BMI above 30 on lifestyle and behavior modifications such as appropriate diet and exercise

• Patient goals should be individually determined

ACP GuidelinesRecommendation #2

• Pharmacologic therapy can be offered to patients who have failed diet and exercise alone

• Doctor-patient discussion of side effects, long term safety data, and temporary nature of weight loss achieved with medications should occur before medication initiation

ACP GuidelinesRecommendation #3

• Medication choices for the obese patient include: sibutramine, orlistat, phentermine, diethylpropion, fluoxetine and bupropion

• The choice of drug should be dependent on the side effect profile and the patients tolerance of the side effects

ACP GuidelinesRecommendation #4

• Surgery should be considered as a treatment option for patients with a BMI over 40 who:– Instituted but failed an adequate exercise and diet

program (with or without adjunctive drug therapy)

AND

– Present with obesity-related comorbid conditions such as hypertension, impaired glucose tolerance, diabetes mellitus, hyperlipidemia and obstructive sleep apnea

• Doctor-patient discussion of surgery should include long term side effects

ACP GuidelinesRecommendation #5

• Patients should be referred to high-volume centers with surgeons experienced in bariatric surgery

Bariatric Surgery

Recommendations for Patient Selection

• Between ages 18 and 50• Stable preoperative weight for 3-5 years• Smoking cessation for at least 6 weeks• Those with psychiatric history require careful

assessment• Tests to predict success of surgery:

– Personality factors– Eating habits– Motivation

Grace DM. Gastroenterol Clin North Am. 1987;16:399.

Types of Surgery: Gastric Bypass

• Roux-en-Y gastric bypass is the most popular in the US

• Pouch can be created with staples or complete division

• Long-term weight loss of 50% of excess body weight

• Moving Roux limbs distally creates more rapid weight loss– Malabsorption problems may be

exacerbated

Types of Surgery: Gastroplasty

• Vertical banded gastroplasty now the preferred type of gastroplasty– Less enlargement over time

• Produces weight loss, but usually less than gastric bypass

Types of Surgery: Gastric Banding

• Problems with original gastric band– Pouch too large or small

• Adjustable gastric band developed in the 1980s– Controls restriction by

injection/withdrawal of saline

• May be performed laparoscopically

Mechanisms

• Operations dramatically restrict gastric size, reducing nutritional intake

• Some types of surgery decrease the absorption efficiency of nutrients

– Roux-en-Y gastric bypass

– Biliopancreatic diversion (BPD)

• Malabsorption procedures create a greater risk for nutritional deficiencies

Side Effects & Complications

• Iron deficiency• Vitamin B12 deficiency• Folic Acid deficiency• Dehydration• Vitamin A deficiency• Electrolyte deficiency• Protein deficiency• Hyperparathyroidism• Follow up of nutritional and

metabolic problems after bariatric surgery K. Fujioka Diabetes Care 28:481-484,2005

• Nausea• Vomiting• Abdominal pain• Constipation• Marginal ulceration• Gallstones• Bleeding ulcer• Obstruction of the stomach outlet

1 in 200-300 patients in the US die from bariatric surgery

Shikora SA. Nutrition in Clinical Practice. 2000;15:13.www.mayoclinic.com. Surgery for obesity: What is it and is it for you?. Accessed February 15, 2005.