13. 20 Years Ago Today
500 calories
1 cup spaghetti with
sauce and 3 small
meatballs
How many calories
do you think are in
today's portion of
spaghetti and
meatballs?
Portion Distortion, HHS, NIH, NHLBI
14. 20 Years Ago Today
500 calories
1 cup spaghetti with
sauce and 3 small
meatballs
Portion Distortion, HHS, NIH, NHLBI
1,025 calories
2 cups of pasta with
sauce and 3 large
meatballs
Calorie Difference: 525 calories
15.
16. “…adding 1 oz of a sugar-sweetened beverage and
walking 1 minute less per day creates a temporary
energy surplus of about 13 kcal/d, leading to a
weight gain of 0.6 kg (1.4 lb). Repeating changes
in diet and physical activity of this magnitude on an
annual basis for 28 years would produce the 370
kcal/d “energy gap” and 16-kg (35-lb) weight gain.”
Journal of the American Medical Association, 2010
23. Bariatric surgery makes people live longer
• 24% reduction in mortality (N Engl J Med
2007)
• 53% reduction in fatal heart attacks
(JAMA 2012)
24. But…
• Increased suicidality (Am J Med 2010)
• Possibly increased alcohol abuse (JAMA 2012)
• Decreased bone mineral density (BMJ 2012)
• Postoperative care is complicated
Hospitalizations roughly doubled (7.9% vs 3.9%) over six years
(JAMA 2012)
27. 1992
34-week trial of extended-release
fenfluramine (Pondimin®) plus 15 mg
phentermine (Clin Pharmacol Ther
1992) versus placebo
Drug group lost 14.2 +/- 0.9 kg, or 15.9% +/- 0.9%
of initial weight (n = 58)
Control group lost 4.6 +/- 0.8 kg or 4.9% +/- 0.9%
of initial weight (n = 54; p<0.001)
29. 1996
Redux® (dexfenfleuramine) is approved over the
objections of several FDA reviewers concerned
with pulmonary hypertension
Weight loss specialists caution that only those
“moderately to severely” obese should take Fen-
Phen
$52 million marketing campaign results in $300
million in sales of Pondimin® and Redux® for
American Home Products (now Wyeth)
• Cohen K, Fen-Phen Nation, pbs.org
31. 1997
Both Pondimin® and Redux® voluntarily
withdrawn from the market on September 15
(Cohen K, Fen-Phen Nation, pbs.org)
Sibutramine (Meridia®) approved November
24
32. 2010
Sibutramine (Meridia®) voluntarily withdrawn
from the marked on October 9
16% increase in risk for major adverse
cardiovascular events
2.5% weight loss at 60 months
(Pollock A, NYTimes.com)
33. 2010: Qnexa®
Combination phentermine/topiramate ER
Patients on Qnexa® lost an average 11% of
their starting weight at one year
Initial approval denied
Cognitive disorders
Metabolic acidosis
Tachycardia
34. Phentermine/topiramate ER
(Qsymia®)
• Approved in adults if:
• BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with at
least one “weight-related condition”
(HTN, dyslipidemia, DM or pre-
DM, abdominal obesity)
Package insert: http://www.vivus.com/docs/QsymiaPI.pdf, accessed 10/10/12
35. 2010: Lorcaserin (Belviq®)
Approval originally denied over FDA
scientists’ concerns about heart-valve risks
Patients lost an average of 3.1% of their
starting weight over a year versus placebo
Approved by FDA June 2012
36. Lorcaserin (Belviq®)
• 10 mg twice daily in addition to diet and exercise if:
BMI >30 kg/m2 or
BMI >27 kg/m2 with “weight-related comorbidities”
• “Cautious use” if heart failure or depression
• Headache, nausea, and dizziness most common adverse
events
• Label recommends discontinuation if <5% of body weight
lost in 12 weeks
Does allow for use for “weight maintenance”
Package insert: http://us.eisai.com/package_inserts/BelviqPI.pdf, accessed 10/10/12
37. Orlistat (Xenical®, Alli®)
• -2.9% weight loss vs. Placebo
• Use limited by stomach discomfort and
greasy stools BMJ 2007
38.
39. “Every system is perfectly
designed to achieve the results
that it achieves.”
Don Berwick, MD
41. “Handing out nutrition brochures
does not work.”
Eileen Kennedy, Dean of the Friedman
School of Nutrition Science and Policy, Tufts
University
42.
43. It’s not like we’re not trying…
40 percent of obese Americans say they’ve
lost >5% of their weight in the last year
Most successful weight losers 1) exercised
more, 2) intentionally ate fewer calories, and
3) used prescription diet medications
Those who lost the most joined a formal
weight-loss program
People who tried to lose weight by eating diet
foods and products were the most likely to
gain weight
American Journal of Preventive Medicine 2012
44.
45. Children are less active today than at any other time in
American history, spending 7.5 hours a day watching
TV, playing video games or simply involved in efforts that
don't require movement
(Xanthakos S, 2010)
46.
47. How much exercise is enough?
(Obesity 2008)
• National Weight Control Registry
• Persons maintaining ≥ 30 lb weight
loss at one year:
• Average 2,621 calories per week in
intentional physical activity
48. “…27% to 30% of the daily caloric intake of American
children and adults is comprised of low nutrient density
food
“…with sweeteners and desserts contributing 18% to 24%
of the total”
(Xanthakos S, 2010)
49. What predicts weight loss in postmenopausal
women? (J Acad Nutr Diet 2012)
6 month weight loss:
Decreased intake of desserts (P<0.001)
Decreased restaurant eating (P=0.042)
Decreased sugar-sweetened beverage intake (P=0.009)
Decreased fried foods (P<0.001)
Increased fish consumption (P=0.003)
48 month weight loss associated with:
Decreased intake of desserts (P=0.003)
Decreased intake of sugar-sweetened beverages
(P=0.011)
Decreased intake of meats/cheeses (P=0.024
Increased fruit/vegetable intake (P<0.001)
50.
51. Sleep may be worth 12 pounds per
year
Volunteers sleeping only 5.6 hours per
night for three weeks experienced an
average 8 percent decrease in resting
metabolic rate
Theoretical weight
gain: one bowling ball
per year
Science Translational
Medicine 2012
52. Justin’s “To Do” list for weight
reduction
Stop drinking calories
Move through space at least 30 additional
minutes per day
Eat at least five servings (cups) of fruits and
vegetables daily
Modify your environment
Go to bed at night
If you don’t sleep well, get tested
If you must work nights, get a new job
If you can’t lose weight, get help
To understand why this is not the equivalent of weight loss surgery, we really need to understand the role of fat and bowel as endocrine organs.
Total weight loss (all procedures) at the time point for which data are available for 50% of the study patients was 38.5 kg (80.5 lbs; 55.9% excess weight loss)Total weight loss at <2 years was 36.6 kg (84.7 lbs; 53.8% excess weight loss)Total weight loss at >2 years was 41.6 kg (91.5 lbs; 59% excess body weight loss) Buchwald H et al, 2009
Doses lower than what’s available separately.
Echocardiographic data from > 5200 participants who got either lorcaserin or placebo for up to 1 year):Relative risk of FDA-defined valvulopathy 1.16 (95% CI, 0.81 to 1.67)