Transcript Pharmacotherapy of Obesity

4th McMaster University Review Course in
INTERNAL MEDICINE
Should I refer my obese patient for bariatric
surgery?
Dr. Khalid Azzam
Assistant Professor of Medicine
HHS Bariatric Medical Clinic
4th McMaster University Review Course in
INTERNAL MEDICINE
Dr. Khalid Azzam has NO potential for conflict of interest with this
presentation
One in Four Adult-Canadians is
Obese
Component of Statistics Canada Catalogue no. 82-625-X
Health Fact Sheets. www.statcan.gc.ca/chms.
Obesity Etiology
• Majority of obese subjects are affected by
common obesity of multifactorial origin
What Causes Common Obesity?
accumulation of body fat
over time
as a result of energy
imbalance
Due to a state where
calorie intake is more
than calorie
expenditure.
Obesity Etiology is Complex
• Obesity is directly
Caused by increased
food intake and
decreased physical
activity in genetically
predisposed individuals,
this process is complex
and does not operate in
a vacuum.
• A wide range of factors
influence obesity;
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–
–
–
–
–
Lifestyle
Social
Psychological
Financial
Cultural an
Environmental
Complications, comorbidities and
barriers to obesity management
Sharma AM. Obesity Reviews (2010) 11, 808–809
Obesity Management
Clinically
Significant
Weight Loss
vs
Cosmetically
Acceptable
Clinically Significant Weight Loss
• Modest weight loss; 5 – 10 % of initial body
weight;
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–
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A realistic goal to achieve
Improves well-being
Improve many of the medical complications
Prevent the development of new obesity-related
illnesses
Impact of Weight Loss on Risk Factors
~5%
Weight Loss
5%-10%
Weight Loss
HbA1c
1
1
Blood Pressure
2
2
Total Cholesterol
3
3
HDL Cholesterol
3
3
Triglycerides
4
1. Wing RR et al. Arch Intern Med. 1987;147:1749-1753.
2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:270-278.
3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S.
4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:264-270.
Modified from slide library
www.obesityonline.com
Armamentarium for Obesity
Treatment
• Bariatric Surgery
• Anti-obesity Drugs
• Behavioral Modification
– Diet & physical activity
Comprehensive Approach to
Obesity Management
• Should not focus on
food and calorie only
Behavior Modification for
Prevention and Treatment
of Obesity
Lifestyle Changes,
Diet & Physical Activity
Cardinal Behaviors of Successful Long-term Weight
Management
• Self-monitoring:
– Daily food records
– Limit certain foods or food quantity
– Weight: check body weight >1 x/wk
• Low-calorie, low-fat diet:
– Total energy intake: 1300-1400 kcal/d
– Energy intake from fat: 20%-25%
• Eat breakfast daily
• Regular physical activity: 2500-3000 kcal/wk (eg, walk 4 miles/d)
Klem et al. Am J Clin Nutr 1997;66:239.
McGuire et al.Int J Obes Relat Metab Disord 1998;22:572.
Diet Principles
• Diet selection depends on the subjects'
preferences and comorbidities;
• Diets with defined number of calories may be
beneficial
– Portion-controlled foods
– Shakes
– food bars
Samaha et al, N Engl J Med 348:2074-2081, 2003
Jeffery et al. J Consult Clin Psychol 1993;61:1038
What is the Evidence for Lifestyle
Interventions?
Look AHEAD (Action for Health in Diabetes)
• Multicenter randomized clinical trial
Intensive lifestyle intervention (ILI)
vs
Diabetes support and education (DSE; the control group)
• Outcome: Incidence of major CVD events
•
5145 overweight or obese individuals with T2DM
(59.5% female; mean age, 58.7 years)
• > 93% of participants provided outcomes data at each annual
assessment.
Arch Intern Med. 2010;170(17):1566-1575
At each session, participants were weighed, self-monitoring records were
reviewed, and a new lesson was presented.
Arch Intern Med. 2010;170(17):1566-1575
Intensive Lifestyle Intervention (ILI)
Diet:
• Calorie goal (1200-1800 kcal/d)
• < 30% of calories fat (10% saturated fat)
• Minimum of 15% of calories from
protein
• Portion-controlled diet (liquid meal
replacements) was used to increase
dietary adherence
Exercise:
• At least 175 min of physical activity / wk
• Activities intensity similar to brisk
walking.
Behavioral strategies:
• Self-monitoring, Goal setting and
Problem solving
Diabetes Support and Education (DSE)
•
Invited to 3 group sessions each year.
•
Sessions used a standardized
protocol and focused on:
– Diet
– physical activity
– social support
•
Information on behavioral strategies
was not presented
•
Participants were not weighed at
these sessions.
Arch Intern Med. 2010;170(17):1566-1575
Look AHEAD
Average effect is the difference between ILI and DSE averaged across the 4 years
Arch Intern Med. 2010;170(17):1566-1575
Arch Intern Med. 2010;170(17):1566-1575
Weight Management Programs
Total Meal Replacement Programs
• 26 weekly sessions
– 12 Weeks of low calorie meal replacement
• 4 high protein shakes (Optifast®) per day total 900 kcals
– Followed by
• Progressive re-introduction of food
• Ongoing Behavioral Modification and
Psychosocial Assessment and Support
The Louisiana Obese Subjects
Study (LOSS)
• intensive medical intervention (IMI) (n=200)
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900-kcal liquid diet for 12 weeks or less
Group behavioral counseling
Structured diet
Choice of pharmacotherapy months 3 to 7
Maintenance strategies for months 8 to 24
OR
• Usual care condition (UCC) (n=190).
– Internet weight management program.
Rayan D, et. al, Arch Intern Med. 2010;170(2):146-154
The Louisiana Obese Subjects Study
(LOSS)
Rayan D, et. al, Arch Intern Med. 2010;170(2):146-154
Percentage of the participants in the LOSS who met weight
loss or gain categories at year 2
Rayan D, et. al, Arch Intern Med. 2010;170(2):146-154
Medications
Orlistat
• Pancreatic lipase
inhibitor
• Works nonsystemically to block
the absorption of
dietary fat
• minimally (<1%)
absorbed from the
gastrointestinal tract
Effect of Long-term Orlistat Therapy on
Body Weight and Diabetes
Change in Weight (kg)
0
37% reduction in the cumulative
incidence of new-onset T2DM
-3
-4.1 kg
Placebo
-6%
-6
-6.9 kg
-9
- 11% Orlistat
P<0.001 vs placebo
-12
0
52
104
Weeks
156
208
(XENDOS) Torgenson et al. Diabetes Care 2004;27:155
Modified from slide library
www.obesityonline.com
Gastrointestinal Side Effects of Orlistat Therapy
Year 1
Placebo
Fatty/oily stool
Increased defecation
Liquid stools
Fecal urgency
Flatulence
Flatus with discharge
Fecal incontinence
Oily evacuation
Low plasma vitamin conc:
Vitamin A
Vitamin D
Vitamin E
Year 2
Orlistat
Placebo
Orlistat
5
7
10
3
3
0
0
1
31
20
13
10
7
7
7
6
1
2
5
2
2
0
0
0
8
2
8
3
3
1
2
5
0.6
0.6
0.9
0.3
5.1
4.6
0.8
0.8
0
0
3.1
1.6
Values are percentage of subjects.
Sjostrom et al. Lancet 1998;352:167.
Recommended by FDA Panel..
Approval Pending
Bariatric Surgery
NIH Consensus Development Panel
Recommendations
• Patients seeking therapy for severe obesity for the first time should be
considered for treatment in a nonsurgical program that integrates a
dietary regimen, appropriate exercise, behavior modification, and
psychological support
• Gastric restrictive or bypass procedures could be considered for wellinformed and motivated patients in whom the operative risks were
acceptable
• Patients who are candidates for surgical procedures should be selected
carefully after evaluation by a multidisciplinary team with medical,
surgical, psychiatric, and nutritional expertise
• Patients should undergo lifelong medical surveillance after surgery.
NIH Consensus Development Panel. Ann Intern Med
1991;115:956.
The Evidence
• Currently, there are no randomized, long-term
studies in existence.
Swedish Obese Subjects
(SOS) Study
• Prospective, non-randomized matched cohort
study
• The largest and longest comparison of bariatric
surgery and medical management.
• 4047 obese subjects.
– Surgery group: 2010 bariatric surgery
– Matched Control group: 2037 “conventionally
treated”
Sjöström et al, N Engl J Med 2004;351:2683-93.
Mortality in SOS
• Mortality benefit after
an average of 10.9
years follow up.
• NNT is 77 to save one
life after 10 years in
SOS subjects.
Sjöström et al, N Engl J Med 2007;357:741-52
Limitations of SOS
• Non-randomized
• Potential treatment bias: The medical management of the
controls varied from no treatment to intensive medical therapy.
• Potential selection bias: patients undergoing surgery healthier.
• The impact of more modern medical management might
narrow the SOS morbidity and mortality
– 13% of the entire SOS cohort had either DM or previous MI or stroke
– < 2% of the cohort was on a statin.
Sjöström et al, N Engl J Med 2004;351:2683-93.
Cons of Surgery
•
•
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•
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Nutrients Malabsorptions
Medications side-effects
No reductions for cost of mediation.. Post op
Mental health issues and addictions
Increase VTE,
Increased Hospitalization
Medications & Nutrients Absorption
• Effect of Gastric Bypass procedures:
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•
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Decreased Drug solubility
Decreased surface area for absorption
Unpredictable site of absorption
Change in gastric PH
– Nutrient deficiency
– Need for lifelong supplements
– Decreased absorption and medication efficacy
Increases Risk for Medication
Adverse Events
• Reduced size of the stomach increases risk for
adverse events associated with
– NSAIDS
– ASA
– Oral bisphosphonates.
Medication Costs
• SOS
• Surgery did not result in decreased medication
costs as
• decreased diabetes and cardiovascular
medications were offset by increased GI tract,
NSAIDs, pain, anemia and vitamin deficiency
medications.
Narbro K, et al. Arch Intern Med 2002; 162:2061-9.
Longitudinal Assessment of
Bariatric Surgery 1 (LABS-1) trial
• Prospective, multicenter, observational Study
• 4776 consecutive patients undergoing bariatric
surgical
• Within 30 days of surgery, 5% of patient has VTE;
reintervention; or failure to be discharged
Flum et al. NEJM 2009;361:445-54
Complications of Bariatric Surgery
All procedures
• Deep vein thrombosis & Pulmonary embolism
• Intractable vomiting
• Nutritional Deficiencies
– Kwashiorkor (Protein malnutrition)
– B1 deficiency (Berberi)
Procedure specific Complications
Gastric banding
procedure
Band slippage
Gastric bypass
Band erosion
Anastomotic leak with
peritonitis
Stomal stenosis
Esophageal dilatation
Marginal ulcers
Band or port infections
Port disconnection
Staple line disruption
Nutrient deficiencies
(iron, calcium, folic acid,
vitamin B12)
Port displacement
Dumping syndrome
Small bowel obstruction
Biliopancreatic
diversion
Anastomotic leak with
peritonitis
Protein-calorie malnutrition
Dehydration
Nutrient deficiencies
Calcium, iron, folic acid, Fat
soluble vitamin (A,D,E,K)
deficiencies
Steatorrhea
Internal hernia
Small bowel obstruction
Internal hernia
Adhesions
Adhesions
Other Factors Influencing Mortality
• Age > 65; 30 day mortality 4.8 %
• Surgeons and Hospitals performing < 100
procedures a year
– OR 2.5 and 2.3 compared to high volume centers
JAMA 2005 Oct 19;294(15):1903-8
Surgery. 2008 Nov;144(5):736-43. Epub 2008 Jul 21
Increased Hospitalization
• Retrospective study of administrative data for patients
undergoing Roux-en-Y gastric bypass in California from 1995
to 2004 .
• 60,077 patients
• 3-year post-operative follow up data was available for 24,678
patients
• Results:
– Pre-procedure hospitalizations occurred in 8.4%
– First post-operative year occurred in 20.2% (NNH=9)
– Second post-operative year 18.4% (NNH=10)
– Third post-operative 14.9% (NNH=16)
Zingmond DS, et al. JAMA 2005; 294:1918-1924.
Post Operative Mortality
• 16,155 Medicare beneficiaries underwent
bariatric procedures between 1997-2002.
– 1-year mortality
– Overall 4.6% (NNH=22)
– Men 7.5% (NNH=14)
– Women 3.7% (NNH=27) and
– Aged 65 years and older 11.1% (NNH=9).
Flum DR ,JAMA 2005; 294:1903-1908
Failure to Lose Weight & Weight Regain
• Regain of lost weight occurs in up to 20% in
2nd and 3rd year post-op
– Noncompliant eating and other behavioral
– Gradual enlargement of the gastric pouch
– Dilation of the gastrojejunal anastomosis
Obes Surg 2002 Apr;12(2):270-5
Am J Surg 1984 Sep;148(3):331-6
Psychosocial Impacts
• Surgery may increase risk for substance
misuse and addictions.
– Neurochemical void caused by restricted food
ingestion
– Substitute other substances or behaviors to boost
dopamine to get the feel-good effect
– Change in alcohol absorption and metabolism
after Gastric Bypass
Med Clin N Am 91 (2007) 451–469
After bariatric surgery, there is higher than
expected;
– Suicide
– Depressions
– Eating disorders
Med Clin N Am 91 (2007) 451–469
• Patients with history of psychiatric disorders should
have appropriate care before and after bariatric
surgery.
• We are not able to fully predict which surgical
patients will have suboptimal weight loss or suffer
from clinically significant psychosocial complications.
• Patients with active psychiatric illnesses, suicidal
ideation and substance abuse should not undergo
surgery.
The Bottom Line
More Evidence is Needed!
• There is need for good-quality, long-term RCTs comparing
different operative techniques and non-surgical treatment for
obesity.
• Theses future studies should include an assessment of
– patient quality of life
– psychosocial consequences of surgery and
– impact on mortality in the context of current treatment trends for
cardiovascular diseases and diabetes.
• Results from ongoing, well-designed studies using intensive
medical therapy in patients with obesity are awaited.
Managing all the modifiable factors contributing to obesity
long-lasting benefits
Cultural
Financial
Psychological
Lifestyle
Environmental
Social
• Patients with severe
obesity should be
treated initially in a
medical program that
focus on
–
–
–
–
Diet
Activity
Lifestyle changes
Behavior modification,
and
– Specialized psychosocial
assessment and support
• Bariatric Surgery is a
useful tool in the
management of obesity
for carefully selected
individuals and is not a
quick fix
• Surgery should be
offered ONLY to
candidates who the
benefits of surgery
outweigh the expected
medical, psychosocial
and financial harms.
• Failure to adhere to
behavior modification
and addressing the
psychosocial
determinants of obesity
cannot be fixed by
bariatric surgery
• Physicians should be
knowledgeable of pros
and cons of bariatric
surgery and the
availability of
alternative treatment
strategies.
Lets Talk Numbers
• 2008-2009 total 2385 procedures in Canada
• Ontario Bariatric Network planned to provide 2000 surgeries
per year
• 5.8 % of Canadian has BMI that qualifies for Surgery App = 1.9
Million
• Assuming that 10% will request Surgery (190,000)
• Requires about 20,000 procedure per year over 10 year
Should I refer my obese patient for bariatric surgery?
Is your patient?
Requesting/Interested in surgical treatment and
Meets the indications for Bariatric Surgery and
Has no contraindications and
the referring physician/practitioner has the expertise and
resources to assess psychosocial, environmental, cultural,
lifestyle and financial barriers and discuss potential
complications
Yes
Refer for Surgery
No
Refer to Medical Bariatric
Assessment/Treatment