obesity treatment in canada: what are the options? - canadian obesity …€¦ · ·...

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

Twells, LK., CMAJ Open, 2014;2(1), E18-E26.

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

“Subdue your appetites, my dear, and

you’ve conquered human nature”

Charles Dickens

BIOLOGY

DEFEND

YOUR

HIGHEST

WEIGHT

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

Hunger: reaction to low level of glucose

If we can’t shut it off = OBESITY

Appetite: The desire for food (OBESITY) Psychological (looks good! smells good!), complicated

neurology

SATIETY: feeling of fullness, satisfaction.

If this isn’t working = OBESITY


Scar Tissue (Gliosis) in the Hypothalamus –

leading to chronic obesity

Thaler et al. Diabetes Vol 62, 2013


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.


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.


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.


Lap Band


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


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


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


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


Barry at 183 kg, BMI 60

• Obesity Class III

• Diabetes Type 2

• OSA – CPAP

• Hypertension

• High Cholesterol

• Developmental Delay

• MEDs

• Metformin, Glyburide

• Ramipril, Lipitor


Barry’s weight loss graph

Start 183Kg, lost 80Kg Now 103Kg


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


Barry’s weight management graph

2007

2014 Regain 110lbs 16% weight loss

2012 Loss 176 lbs 43% weight loss

Lifestyle Management

DON’T GIVE UP

Medications for

weight management

EXCITING AND EFFECTIVE

Bariatric Surgery – Diabetes and

Weight Management

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

Thank You!

[email protected]

Sarah Vanderlelie, BSc

Jasmine Lee, MSc

Jennifer Kuk, PhD

Kristin Serodio, MSc

Arya Sharma, MD, PhD

Marcia Villafranca

WMC Team

obesity treatment in canada: what are the options? - canadian obesity …€¦ · ·...

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