Nadia Ahmad, MD, MPH

Founding Director

Obesity Medicine Institute, Dubai

American Board of Obesity Medicine

drahmad@obesitymedicineinstitute.com

971 55 452 8476

February 24, 2016

Top 3 physician barriers to obesity treatment

• Lack of recognition of obesity as a chronic and progressive disease

• Lack of education and training

• Time constraints

Mauro, Marina, et al. "Barriers to obesity treatment." European Journal of Internal Medicine 19.3 (2008): 173-180.

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

There are 33 distinct therapies for obesity

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

Lifestyle: Diet

IS A CALORIE A CALORIE?

Some studies say “Yes”

Meta-analysis of RCTs comparing various diets

Conclusion: There is minimal difference in weight loss among various diets,

and the degree of difference is not meaningful for those seeking to lose weight

Johnston et al. JAMA. 2014;312(9):923-933

Considerable variation in response to diets

Zone Diet

0

10

20

30

>10%

Gain

5-

10%

Gain

0-5%

Gain

0-5% 5-

10%

10-

15%

15-

20%

20-

25%

25-

30%

0

10

20

30

>10%

Gain

5-

10%

Gain

0-5%

Gain

0-5% 5-

10%

10-

15%

15-

20%

20-

25%

25-

30%

0

10

20

30

>10%

Gain

5-

10%

Gain

0-5%

Gain

0-5% 5-

10%

10-

15%

15-

20%

20-

25%

25-

30%

0

10

20

30

>10%

Gain

5-

10%

Gain

0-5%

Gain

0-5% 5-

10%

10-

15%

15-

20%

20-

25%

25-

30%

Atkins Diet

LEARN Program Ornish Diet

Weight Change Weight Change

Weight Change Weight Change

Adapted from Gardner et al, JAMA 2007

Dansinger et al. (2005) JAMA.

Diet adherence correlates to weight loss

But which comes first?

Weight change

Adherence

Effect of simple calorie deficit on obesity

Reduce caloriesSet point

unchanged

Physiological

compensation

Short-term

weight loss

↑ appetite

↓ energy

expenditure

↓ adherence

to the dietWeight regain

Rosenbaum et al. Brain Res. 2010 September 2; 1350: 95–102

Indications for caloric reduction (i.e. short-term weight loss)

• Prior to a therapeutic procedure or operation, in order to medically qualify for

procedure or improve prognosis after treatment.

Examples:

Orthopedic surgery

Transplant surgery

In vitro fertilization

• Prior to a diagnostic or therapeutic procedure in which weight and/or size is

prohibitive due to equipment limitations.

Examples:

CATscan or MRI

Radiation therapy

Interventional cardiology procedure

Interventional radiology procedure

Effect of diet composition change on obesity

Set point

lowered

Physiological

reinforcement

Change food

signaling

↓ appetiteInvoluntary ↓

calorie intake

Long term

weight loss

Nutrients function as hormones: critical for metabolic processes and energy regulation

Fe

Amino

AcidsSCFA

s

B12

Fructose

glucose

Vit D

Ca

glucose

glucoseglucose

SCFA

s

SCFA

s

Ca

Ca

Ca

Ca

Ca

Fe

Fe

Fe

Fe

Vit DB12

B12B12

Vit DFructose

Fructose

Fructose

Amino

Acids

Amino

Acids

Amino

Acids

Ideally, diet therapy should be matched to the patient’s underlying biology

Lifestyle: The healthy diet (pro-metabolic)

What

• Eat good protein• low-fat dairy, eggs, lean meats, legumes

• Eat whole grains

• Eat a variety of fruits & vegetables

• Include nuts

• Drink plenty of water

• Avoid WHITE• white sugar, white breads, white pasta

• Avoid processed foods

• Avoid fried foods

• Avoid sugar-sweetened beverages

• EtOH only in moderation when culturally applicable

How

• Maintain a regular structure • Brkfst-Snack-Lunch-Snack-Dinner

• Eat mindfully• no distractions

• chew slowly

• recognize hunger and satiety cues

Lifestyle: Activity

• Moderate intensity > 30 min. 5 times / wk

• Resistance training 2 times / wk

• Flexibility and balance exercises esp. for

postmenopausal women and older men

• Focus on activity duration/ intensity /

type and not on calories expended

• Physically realistic

• Practical enough to fit into the patient’s

routine

Weight loss response to activity is variable

>5 gain 5-2.5 gain 2.5-0 gain 0-2.5 2.5-5 5-7.5 7.5-10 10-12.5 >12.50.0

5.0

10.0

15.0

20.0

25.0

30.0

Total Weight Loss (Kg)

No

. o

f S

ubje

cts

Weight loss with 8 Kcal/kg/wk exercise over 6 months

in post-menopausal women

Adapted from Church, et al., PLOS One 2009.

Lifestyle: Sleep Strategies

Sleep Hygiene

Avoid caffeine, nicotine, alcohol

Make bedroom sleep-inducing

Establish soothing pre-sleep routine

Go to bed when truly tired

Don’t be a night-time clock-watcher

Use light to your advantage

Be consistent with sleep schedule

Nap early or not at all

Lighten up on evening meals

Balance fluid intake

Exercise early

Follow thru

Sleep aids

Melatonin*

Lifestyle: Stress Management

• Yoga

• Meditation

• Mindfulness

• CBT

• Life coaching

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

The first step in anti-obesity pharmacotherapy is NOT adding a medication

The first step in anti-obesity pharmacotherapy is NOT adding a medication

It’s removing medications.

Weight gain-promoting meds and alternatives

Weight gain-promoting meds and alternatives, con’t

Weight gain-promoting meds and alternatives, con’t

Principles of anti-obesity pharmacotherapy

1. Indications: BMI ≥ 30 or

BMI ≥ 27 plus co-morbidities

2. Not for short term use- Short trial to determine if the medication

works in an individual

- ≥ 5% total weight loss in 12 weeks

3. Continue only in responders

4. Consider combinations with

complimentary action

Smith et al. NEJM 2010;363:245-56 >5% gain 5-0% gain 0-5% 5-10% 10-15% 15-20% 20-25% 25-30% >30 %0

10

20

30

% Total Weight Loss

Pe

rce

nta

ge

of

Su

bje

cts

Response to Liraglutide 3.0 mg at 52 weeks

Prescribing information of Liraglutide 3.0 mg (Saxenda)

Anti-obesity medications

Metformin

Phentermine + Topiramate

(Qsymia)

Topiramate

Weight loss

Medications

Adrenergic Anti-epileptic Other

Phentermine

Anti-diabetes

Exenatide

Zonisamide Pramlintide

SGLT-2

inhibitors

Lorcaserin

(Belviq)

Orlistat

Bupropion +

Naltrexone

(Contrave)

Liraglutide

(Saxenda)

Bupropion

US FDA-approved

Off-label

Drug Mechanism of action % Weight

loss

Phentermine1 ⬆ Norepinephrine in hypothalamus 8.1

Phentermine +

Topiramate ER 2** Modulation of GABA-ergic pathways 8.8

Bupropion SR +

Naltrexone3

⬆ Norepinephrine and dopamine in

hypothalamus and reduced auto inhibition5.2

Lorcaserin4 ⬆ Selective activation of serotonin 2c

receptors in the hypothalamus.4.8

Liraglutide5 Long acting human GLP-1 agonist 4.5

Orlistat6 Inhibitor of intestinal lipase 3.8

1. Glazer, Arch Intern Med. 2001

2. SEQUEL study group, AJCN 2011

3. Apovian, et al. Obesity 2013

4. Smith, et al, NEJM 2010

5. Data presented for FDA approval 2014

6. Torgorson, et al, Diabetes Care 2004

How to choose a medication

Contraindications and SE profile

Efficacy

Cost to patient

Patient preference

Dual benefit indication

Availability

Basic algorithm for monotherapy with an anti-obesity agent

Start low dose

Poor effect at high dose

since med start

Good effect

≥5% in 12 wks

dose

F/U 1 month

F/U 3 months

Poor effect

< 5% in 12 wks

Same dose

F/U q 3months

Side effects

D/C med or

dose

D/C agent

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

Bariatric Surgery: Who gets it?

• BMI > 40 kg/m2

• BMI 35-40 kg/m2 with a major

comorbidity

• Recent AACE/TOS/ASMBS

guidelines have broadened

these indications to BMI 30-40

kg/m2 with a major comorbidity

• Adults and adolescents

• No upper limit on age

Bariatric Surgery: How does it work?

• Not restriction or malabsorption

• Physiologic change in the set point

• Changes in neurohormonal gut-

brain communication

What happens to gut hormones on a diet?

Sumithran et al. NEJM 2011; 365:1597-1604.

PY

Y

C

CK

Am

ylin

Ghre

lin

What happens to gut hormones after RYGB?

Time after start of meal (min)

0 20 40 60 80 100

Active G

LP

-1 (

pg/m

l)

0

50

100

150

200

250

300RYGB

Sham

Lean

5 min mixed meal

-10

*

#

*

**

GLP-1

Time after start of meal (min)

0 20 40 60 80 100

PY

Y (

pg

/ml)

0

50

100

150

200

250

300RYGB

Sham

Lean

5 min mixed meal

-10

*

**

**

**

Time after start of meal (min)

0 20 40 60 80 100

PY

Y (

pg

/ml)

0

50

100

150

200

250

300RYGB

Sham

Lean

5 min mixed meal

-10

*

**

**

**

PYY

Time after start of meal (min)

0 20 40 60 80 100

Active

Am

ylin

(p

g/m

l)

0

50

100

150

200

250

5 min mixed meal

-10

*

*

Amylin

Time after start of meal (min)

0 20 40 60 80 100

Acyl

ate

d G

hre

lin (

pg/m

l)

0

50

100

150

200

250

300 RYGB

Sham

Lean

5 min mixed meal

-10

**

Ghrelin

Shin et al., 2010

RYGB is the opposite of restrictive dieting

Diet RYGB

Energy expenditure

Appetite

Hunger

Satiety

Reward-based eating

Stress response

Gut peptides

Ghrelin

GLP-1, PYY, CCK, amylin

Courtesy of Lee M. Kaplan, Harvard Medical School

Bariatric Surgery: Variability in response

RYGB

Bessler at al. (2007) Surg Obes Rel Dis.

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

Gastric band

Gastric balloon

Gastric dual balloon

Endoluminal sleeve

Vagal stimulator

Half have 40-60% EBWL

Half have minimal response

10.5% weight loss vs. 4.7%

with diet and exercise alone

* 6 months

25% EBWL compared to 11.3%

with diet and exercise alone

* 6 months

8.5% greater excess

weight loss at 12 months

with gastric electrical

stimulation compared to

control.

35% EBWL and HgA1c

decrease from 8.8 to 6.4%

at 1 year in uncontrolled

study

(not approved in US)

MECHANICAL PHYSIOLOGIC

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

There are 33 distinct therapies for obesity

Lifestyle-based

therapies

Anti-obesity

medicationsWeight loss

devices

Metabolic

surgeries

6 17 5 5

33 Mono-therapies=

528 Potential Dual Combinations

Step 2: Lifestyle Therapy (diet, activity, sleep, stress)

Step 3: Pharmacotherapy (Rx)

Step 4: Surgical Therapy (Sx)

Step 5: Combine Sx +

Rx

Everyone

Overweight with comorbid.

or BMI ≥ 30 + Inadequate

response to lifestyle

BMI ≥ 35 with comorbidities or BMI ≥

40, + Inadequate response to

lifestyle OR lifestyle + meds

Suboptimal response to surgery or

post-surgical weight regain

Step 1: Remove weight gain-promoting

medications

Everyone

(when

possible)

Consider referring

Always refer to bariatric

surgical center

Refer if 1-2 medication trials are

ineffective or advanced

combinations are needed

Refer if ineffective over 6

months and not comfortable

initiating pharmacotherapy

Refer if significant weight gain

on medication and complexity

of medical decision-making

requires consultation

INDICATIONS WHEN TO REFER

Working algorithm for obesity management

Nadia Ahmad, MD, MPH

Founding Director

Obesity Medicine Institute, Dubai

American Board of Obesity Medicine

drahmad@obesitymedicineinstitute.com

971 55 452 8476

February 24, 2016