Download Overcoming Challenges in the Management of Obesity: A Closer

5/6/2013
Overcoming Challenges in the
Management of Obesity:
A Closer Look at Emerging
Therapeutic Options
Tirissa J. Reid, MD
Assistant Professor, Division of Endocrinology
Weight Control Center, Columbia University Medical Center
Bariatric Clinic, Harlem Hospital
New York, New York
• Disclosures: NONE
• I will not be discussing off-label medication use
1
5/6/2013
Objectives
• Review definition of obesity and prevalence
• Review guidelines for obesity treatment
• Review specific therapies for obesity
– Lifestyle
– Pharmacotherapy
• Focus on emerging pharmacologic options
– Mechanism of action
– Efficacy
– Safety
– Managing Adverse Effects
• Considerations for patients with multiple co-morbidities
– Surgery
What is the definition of obesity?
BMI (kg/m2)
Underweight
Obesity Class
< 18.5
Normal
18.5 - 24.9
Overweight
25.0 - 29.9
Obesity
30.0 - 34.9
35.0 - 39.9
I
II
≥ 40
III
Morbid Obesity
2
5/6/2013
Obesity Trends* Among U.S. Adults
BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2000
1990
2010
No Data
<10%
10%–14%
15%–19%
20%–24%
25%–29%
≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Medical Complications of Obesity
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Nonalcoholic fatty liver
disease
steatosis
steatohepatitis
cirrhosis
Gall bladder disease
Idiopathic intracranial
hypertension
Stroke
Cataracts
Coronary heart disease
Diabetes
Dyslipidemia
Hypertension
GERD
Severe pancreatitis
Gynecologic abnormalities
abnormal menses
infertility
polycystic ovarian syndrome
Osteoarthritis
Skin
Cancer
breast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate
Phlebitis
venous stasis
Gout
3
5/6/2013
A Guide to Selecting Treatment:
National Institutes of Health (NIH) Guidelines*
Body Mass Index (BMI) (kg/m2)
Treatment
Diet, physical
activity,
behavior
therapy
Pharmacotherapy
25–26.9
27–29.9
30–34.9
35–39.9
≥40
Yes with
comorbidities
Yes with
comorbidities
Yes
Yes
Yes
Yes with
comorbidities
Yes
Yes
Yes
***
Yes with
comorbidities
Yes
Weight-loss
surgery
*Yes alone indicates that the treatment is indicated regardless of the presence or absence
of comorbidities. The solid arrow signifies the point at which therapy is initiated.
*** The FDA has approved use of LAGB for patients with BMI > 30 who also have at least one condition linked to
obesity, such as heart disease or diabetes.
NIH/NHLBI, NAASO. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.
Bethesda, Md: NIH; 2000.
Weight Loss Treatments
-Lifestyle Changes
-Pharmacotherapy
-Bariatric Surgery
4
5/6/2013
Non-Pharmacologic Therapy for
Obesity
Lifestyle changes
Lifestyle Changes
• Behavior Therapy
• Diet
• Exercise
5
5/6/2013
Behavior Therapy
• Self-monitoring: includes recording dietary intake (food
choices, amounts, times), exercise and changes in body
weight.
• Stimulus control: identify and change cues that are
associated with eating too much and exercising too little.
For example, limiting exposure to food or separating
eating from other activities such as reading or watching
television.
Behavior Therapy (cont.)
• Reinforcement: encourages attainment of difficult
to achieve goals. Reinforcement may come from
a social support network or getting non-food
rewards for reaching goals or maintaining healthy
lifestyle changes.
• Stress management: helps coping with stressful
events by developing outlets besides eating for
reducing stress.
Evaluating setbacks and
determining how to do better next time can break
the chain of negative thinking and self-punishment
when lapses occur.
6
5/6/2013
Dietary Therapy
• Main component for weight loss is to create a
calorie deficit.
• Recommend a plan based on your patient’s food
preferences. Many eating plans work.
• Present them a few meal plan options:
– Meal replacements, pre-packaged food (most structure)
– Calorie counting
– Specific meal plan
• Have handouts/resources to help them with
dietary changes or write down options for them.
• Food diary
• Referral to Nutritionist
•RCT of 160 overweight/obese adults (mean BMI 35, range 27-42)
w/HTN, HL, or fasting hyperglycemia, randomized to 1 of 4 diets:
Atkins (carbohydrate restriction/high fat)
Zone (high protein)
Weight Watchers (caloric restriction)
Ornish (fat restriction/high carb)
•After 2 months, pts chose own level of dietary adherence
RESULTS at 1 yr:
adherence- low for all diets (50-65%)
wt loss- modest in all groups (4-7 lbs)
cardiac risk markers- improvement in all groups: decr
LDL/HDL by 10%, decr CRP, decr insulin
CONCLUSION: macronutrient composition did NOT determine
degree of improvement in wt or cardiac risk markers; dietary
adherence did.
Dansinger ML, et al. JAMA. 2005 Jan 5; 293(1):43-53.
7
5/6/2013
Exercise
• Counters tendency to regain weight due to:
– More efficient muscles (burn less calories for
same amount of activity)
– Baseline calorie expenditure is lower (carrying
around less weight burns less calories than prev)
– For every 1 lb. lost, pts burn 8kcal/day less.
• Start where patient is and slowly build
Hill, J et al. (2005)J Am Diet. 105;(suppl 1): S63-S66
Greenberg, I et al. (2009) J Am Coll Nutr, 28, 2:159-68.
Physical Activity Recommendations
• 1st recommendation to reduce chronic disease risk:
30 minutes of moderate-intensity aerobic activity x 5d
(150 min/week).
• 2nd recommendation to help manage body weight
and prevent weight gain in adulthood: 60 minutes of
moderate PA most days of the week (300 min/week).
• 3rd recommendation to prevent weight regain: 60-90
minutes of moderate PA most days of the week (350
min/week).
• Strength training on 2 or more days a week for ≥20
minutes each time.
2010 Dietary Guidelines; Look AHEAD
Lifestyle Modification For Obesity Tom Wadden 2012
8
5/6/2013
Pharmacotherapy for Obesity
• Short-term
• Long-term
Weight effects of common chronic
medications
Medication
Class
WT GAIN
WT LOSS/
NEUTRAL
Antidepressants/
Anti-psychotics
TCA’s, SSRI’s/
Seroquel
Wellbutrin
BP meds
Beta-blockers
Anti-epileptics
Gabapentin
CCBs, ACE-I,
ARBs
topiramate,
zonisamide
9
5/6/2013
Impact of Anti-Diabetic Therapies on Weight
GAIN
NEUTRAL
LOSS
Sulfonylurea
Non-sulfonylurea
secretagogues
(Prandin)
Metformin
TZDs
α-Glucosidase
Inhibitor
(Acarbose)
GLP-1 agonist
(Byetta/Victoza)
Insulin
DPP4-Inhibitor
(Januvia)
Pramlintide
(Symlin)
Nathan et al Diabetes Care 31:1-11, 2008
Short-term Pharmacotherapy
Noradrenergic Medications
10
5/6/2013
Noradrenergic Agents
• Schedule IV drugs have a low potential for abuse
• Phentermine (Adipex-P, Fastin): 18.75-37.5 mg/day
• Phentermine resin (Ionamin): 15-30 mg/day
• Diethylpropion (Tenuate, Tenuate Dospan):
25 mg 3x/day or sustained release 75 mg/day
• Phenylpropanolamine (Dexatrim, Acutrim):
withdrawn from market due to association with
hemorrhagic stroke
Yanovski NEJM 346:591 2002
Noradrenergic Agents
(cont’d)
• Approved by the FDA for short-term use:
~ 3 months
• Studies show between 2-10 kg weight loss
over placebo
• Adverse effects: insomnia, dry mouth,
constipation, palpitations, hypertension
11
5/6/2013
Long-term Pharmacotherapy
• Orlistat
• Lorcaserin
• Qsymia
Orlistat (Alli/Xenical)
Mechanism of Action
30% of fat not absorbed
12
5/6/2013
Subjects (%) who Lost > 5% and >10% of Initial Weight after 1 Y Orlistat or Placebo.
Data are from Trials in Europe, the U.S., and in Subjects With Diabetes*
Percent of Subjects
80
> 5% Weight Loss
> 10% Weight Loss
Orlistat
Placebo
60
40
20
0
Europe
U.S.
Diabetes
Europe
U.S. Diabetes
* Lancet 1998;352:167–72; JAMA 1999;281:235–42; Diabetes Care 1998;21:1288–94
Klein S. Am J Clin Nutr 1999;69:1061–3
Orlistat Adverse Effects
• Adverse effects:
–
–
–
–
abdominal discomfort
oily spotting
flatulence with discharge
fecal urgency and incontinence
• Absorption of fat-soluble vitamins and some
medications (e.g. Cyclosporine, levothyroxine,
warfarin) may be affected.
• Liver failure?
• Managing adverse effects
Sjöström L, et al. Lancet. 1998;352:167172.
13
5/6/2013
Lorcaserin (Belviq)- Mechanism of Action
• Selective serotonin R agonist
• Doesn’t bind to 5HT-2b R’s on heart, as
non-specific fenfluramine did
• Binds to 5HT-2c R’s in hypothalamus
• Activates POMC neurons and ultimately
induces a feeling of satiety with a decr in
food intake -> wt loss.
Sargent B and Henderson A. Current Opinion in Pharmacology. February 2011, 11(1): 52–58
Lorcaserin:
selective
Serotonin
receptor 5-HT2c
Agonist
(no valvulopathy)
Smith SR et al. N Engl J Med 2010;363:245-256
14
5/6/2013
Lorcaserin Adverse Effects
• Headaches (16.8% lorcaserin vs 10.1% placebo)
• Dry Mouth
• Fatigue
• Nausea
• Vomiting
NOT YET
AVAILABLE
• Dizziness
Hoy SM. Drugs March 2013, epub.
Smith SR et al. N Engl J Med 2010;363:245-256
Qsymia- Mechanism of Action
• Phentermine
– Increase in NE -> incr metabolism
-> incr locomotor activity
– Increase in DA -> decr appetite
• Topiramate
– Decr appetite via unknown mechanism
Smith, et al, Annals of Pharmacotherapy March 2013, 47:340-349
15
5/6/2013
Qsymia
(phentermine/topiramate)
Randomized, placebo-controlled extension study of
controlled release phentermine/topiramate (Qsymia)
Garvey et al, AJCN 2012,95:297-308
Qsymia and Progression to DM2
Garvey et al, AJCN 2012,95:297-308
16
5/6/2013
Qsymia Adverse Effects
•
•
•
•
•
•
Dry mouth
Dizziness
Constipation
Insomnia
Dysgeusia
Paresthesia
•
•
•
•
•
•
•
Headache
Nephrolithiasis
Depression
Anxiety
Irritability
Disturbance to attention
CLEFT PALATE
Garvey et al, AJCN 2012,95:297-308
Smith, et al, Annals of Pharmacotherapy March 2013, 47:340-349
Qsymia Adverse Effects
• Preventing Adverse Effects
– Do not use in patients w/glaucoma or recent MI/CVA
– Cleft palate: Effective contraception
– Renal Stones: Increase H2O intake, drink crystal light
• Managing Adverse Effects
–
–
–
–
Insomnia: dosing schedule
Fatigue/difficulty concentrating: slow titration
Constipation: increase fiber & H2O intake
Paresthesias: take 1 alka-seltzer daily
17
5/6/2013
Pharmacologic management of obesity
in patients with multiple co-morbidities
Hyperlipidemia
– Xenical: leads to sig decr in total cholesterol,
LDL-C and TGs over wt loss alone
Lindgarde F. J. Intern. Med. 248, 245–254 (2000).
Pharmacologic management of obesity
in patients with multiple co-morbidities
Diabetes
-Qsymia (?)
18
5/6/2013
Weight Reduction: Pharmacotherapy
– Initiate when weight goals are difficult to
achieve or maintain through diet and physical
activity
– Set realistic goals
– Administer for the long term
– Always use in conjunction with diet, physical
activity, and behavior therapy
– Future therapies may involve a “cocktail” of
different medications targeting different
pathways
• Contrave- bupropion/naltrexone
• Empatic- bupropion/zonisamide
Non-Pharmacologic Therapy for
Weight Loss
Bariatric Surgery
19
5/6/2013
ADJUSTABLE
GASTRIC BAND
ROUX-EN-Y
GASTRIC BYPASS
SLEEVE
GASTRECTOMY
SLEEVE GASTRECTOMY
20
5/6/2013
ROUX-EN-Y GASTRIC BYPASS
Remission of Weight-Related
Co-Morbidities after RYGB
• HTN- 50% w/complete resolution; remainder
w/decr in meds
• Sleep apnea- 40% w/resolution; 70% of remainder
of pts have apneic episodes reduced to minimal
amounts
• Improved QoL
• Decr disability
• DM2 - resolution in 70-84% (1-2 yrs)
- sustained resolution in 36% (10 yrs)
L Sjöström. International Journal of Obesity (2008) 32, S93–S97
Sjöström et al, NEJM 2004; 351:2683-93
21
5/6/2013
Remission of DM
BAND:
48%
BYPASS: 84%
Buchwald et al, JAMA 2004; 292:1724-37
Sjöström et al, NEJM 2004; 351:2683-93
Weight Recidivism after Bariatric
Surgery
• Successful RYGB: ≥50% EBW remains off
at 5 yrs
• Success rate w/RYGB = 70%
• Success rate w/LAGB = 50%
Choban PS, et al. Cleveland Clin J Med. 2002 Nov; 69 (11):897-903.
22
5/6/2013
SUMMARY- Obesity Therapy
• Use a stepwise approach
• Remember that lifestyle changes are framework for
success w/meds & surgery
• Prior to adding anti-obesity meds, review pt
medication list for chronic meds which cause wt
gain and change to therapeutic alternatives which
are wt neutral or cause wt loss
• Plan to use medication therapy long-term, as
obesity is a chronic disease
• Surgery may provide durable wt loss for some,
others may benefit from adjunctive medication
therapy if they experience wt regain
Thank you!
23
5/6/2013
Acknowledgements
• CUMC Weight Control Center
–
–
–
–
–
Judith Korner, MD, PhD, Director
Salila Kurra, MD, Physician
Heather Bainbridge, RD, Dietician
Gerardo Febres, MD, Research Coordinator
Ellen Charles, Research Assistant
• Harlem Hospital Bariatric Clinic
– Leaque Ahmed, Surgeon
24