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Obesity Treatment in
Canada: What are the
options?
Dr. Sean Wharton, MD, FRCPC, PharmD
Diplomat American Board of Obesity Medicine
Adjunct Professor McMaster University
Lead Authour – Weight Management Section CDA
Guidelines
Conflict of Interest
Grants (Academic)
MITACs, CIHR
Honoria/Ad Boards
Lilly, Novo Nordisk, Astra Zeneca, Merck, Sanofi, Canadian Diabetes
Association, Canadian Obesity Network
Employment
Hamilton Health Sciences, Toronto East General, York University,
Wharton Medical Clinic
No financial disclosures for this talk
Any off label medication use will be academic
Pulmonary disease abnormal function
obstructive sleep apnea
hypoventilation syndrome
Nonalcoholic fatty liver
disease steatosis
steatohepatitis
cirrhosis
Coronary heart disease
Diabetes
Dyslipidemia
Hypertension
Gynecologic abnormalities abnormal menses
infertility
polycystic ovarian syndrome
urinary incontinence Osteoarthritis
Skin fungal/bacterial infections
Gall bladder disease
Cancer breast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate
Phlebitis/DVT (Blood Clots) venous stasis
Gout
Medical Complications of
Increased Weight
Stroke
Cataracts
Severe pancreatitis
For internal use only Liraglutide is not approved for weight management
Hyperphagia contributes to elevated obesity rates: Humans are eating more, portion size effects
Kelly MT et al. Br J Nutr 2009;102:470–477; CDC. The new (Ab)normal. available at: http://makinghealtheasier.org/newabnormal
80
70
60
50
40
30
10
0
20
Day 1 Day 2 Day 3 Day 4
Study day and meals
Mean c
um
ula
tive E
I (M
J/d)
Men increase energy intake by 17%, women by 10% when presented with large portions versus standard portion
meals; no compensation observed for increased intake over 4 days
CDC, Centre for Disease Control; EI, energy intake
2011 National Obesity Summit Workshop
Obesity is a Chronic,
Progressive, Relapsing
Medical Condition Realistic goal
No quick fix
Long-term maintenance of weight reduction:
meta-analysis - LIFESTYLE MODIFICATION
13 Studies
1,081pts
6 months
14%
We
igh
t
Anderson et al. Am J Clin Nutr, 2001
4.5 years
3% Weight Loss
average
Appetite: The desire for food (OBESITY) Psychological (looks good! smells good!), complicated
neurology
For internal use only Liraglutide is not approved for weight management
Scar Tissue (Gliosis) in the Hypothalamus –
leading to chronic obesity
Thaler et al. Diabetes Vol 62, 2013
For internal use only Liraglutide is not approved for weight management
Multiple hormones play a key role in hunger/appetite and satiety
BBB, blood-brain barrier; CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; PYY, peptide YY . Suzuki K et al. Exp Diabetes Res. 2012;2012:824305.
Amylin Insulin PYY
GLP-1 CCK
Satiety
Hunger
Pancreas Intestines
Ghrelin
Stomach
BBB
Hypothalamus
Leptin Adiponectin Satiety
BBB
BBB
Hypothalamus
Hypothalamus
Leptin (trying to keep you thin)
Leptin
Stop eating
Increase metabolism
Klok, MD., et al., Obes Rev. 2007;8(1):21-34.
For internal use only Liraglutide is not approved for weight management
Bariatric Surgery Effect on Cardiovascular Risk A Systematic Review and Meta-Analysis of 22,090 Patients
% r
eso
lve
d
62% 70%
77% 86%
Hypertension Dyslipidemia Diabetes Sleepapnea
Buchwald H, et al. JAMA 2004;292:1724.
For internal use only Liraglutide is not approved for weight management
Metabolic Surgery Roux-en-Y Gastric Bypass Sleeve Gastrectomy
•Neuro-Hormonal Sx
• 30-35% Weight Loss
•BMI >40, or BMI 35 – 40 with diabetes
•Mortality 1/500 (0.2%)
Morino M et al. Ann Surg. 2007;246(6):1002-7.
For internal use only Liraglutide is not approved for weight management
The Hindgut Theory
• The rapid delivery of nutrients to the distal bowel upregulates the production of L-cell derivatives like GLP-1, Peptide YY
• Increase of post prandial GLP1, PYY after surgery
Mason E. Obes Surg 2005;15:459-461.
Rubino et.al, Ann Surg, 2006;244(5):741-9.
Schmidt, JB et al. IJO 2015
For internal use only Liraglutide is not approved for weight management
Change in body weight (%)
-8
-6
-4
-2
0
2
4
6
8
Treatment period Run-in Follow-up S
n=156 n=144
Change in b
ody w
eig
ht
(%)
Time (weeks)
-14 -12 -10 -8 -6 -4 -2 0 2 4 6 10 14 18 22 26 30 34 38 44 50 56 60 64 68
Mean (±SD); Full analysis set. S, screening period
Liraglutide 3.0 mg
Placebo n=207 n=206
-6.0% -0.2%
-6.2%
-4.1%
+0.3%
Wadden et al. Int J Obes (Lond) 2013;37:1443–51.
Weight Management Medications Canada - 2015
•Orlistat (Xenical) – 1999
•Liraglutide 3.0mg (Saxenda) - 2015
Weight Management Medications US - 2015
• Phentermine - 1959
• Orlistat – 1999
• Phentermine/Topiramate (Qsymia) - 2013
• Lorcaserin (Belviq) - 2014
• Bupropion/Naltrexone (Contrave) -2014
• Liraglutide 3.0mg (Saxenda) - 2014
3.1
8.4
3.2 4.0
5.0
7.4 7.2
9.2
0123456789
10
Weig
ht
Lo
ss (
%)
Medication
Wharton S, Serodio K. Curr Card Rep April 2015
Average Placebo-Subtracted
Weight Loss
For internal use only Liraglutide is not approved for weight management
Pharmacotherapy and Surgery improves adherence to a lifestyle change
Adapted from Lau DCW et al. Can Med Assoc J 2007;176 (8 suppl):S1-S13
Overweight
BMI 25 kg/m2
Obese Class 1
BMI 30 kg/m2
Obese Class 2 BMI 35 kg/m2
Surgery
Pharmacotherapy
Health behaviour modification
1. Increase the number of patients
responding to lifestyle
2. Increase the magnitude of
the response
3. Increase the duration
of the response
For internal use only Liraglutide is not approved for weight management
Obesity Treatment Success
Adapted from Lau DCW et al. Can Med Assoc J 2007;176 (8 suppl):S1-S13
LS + Pharmacotherapy ~ 5-15%
LS + Surgery ~ 20-40%
Lifestyle (LS) ~ 1-5%
0
Years
1 2
For internal use only Liraglutide is not approved for weight management
Barry at 183 kg, BMI 60
• Obesity Class III
• Diabetes Type 2
• OSA – CPAP
• Hypertension
• High Cholesterol
• Developmental Delay
• MEDs
• Metformin, Glyburide
• Ramipril, Lipitor
For internal use only Liraglutide is not approved for weight management
Barry’s weight loss graph
Start 183Kg, lost 80Kg Now 103Kg
For internal use only Liraglutide is not approved for weight management
Barry at 103kg, BMI 33 80kg lost, 43% WL
•Current Medical Hx • Obesity Class I
• OSA • CPAP turned down
• Diabetes type 2 • Diet controlled
•Current Medications • No medications • Off – metformin,
ramipril, glyburide. Lipitor
For internal use only Liraglutide is not approved for weight management
Barry’s weight management graph
2007
2014 Regain 110lbs 16% weight loss
2012 Loss 176 lbs 43% weight loss
Conclusions
Neuroscience explains obesity
Biology – defend highest weight, hormones
adjust to achieve this
Treatments must work to increase satiety
Bariatric surgery and anti-obesity drugs act on
brain systems
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