Obesity Epidemic Mohammed I. Tarrabain, M.D - PowerPoint Presentation

Slide1

Obesity Epidemic

Mohammed I. Tarrabain, M.D

St.Vincent

Medical

Group

IAFP Spring CME & Research Day

May 7,

2015Slide2

The Obesity Epidemic

In the United States, it is estimated that 93 million Americans are affected by obesity. 

In 2001, the states with the top five percentages for obesity were Mississippi, West Virginia, Michigan, Kentucky and

Indiana.

Indiana- Overweight

and

Obesity (2010)

2/3

rd

(65.9%) overweight

, with a

BMI of 25

or greater.

1/3

rd

(29.6%) obese

, with a

BMI

of 30 or greater.

CDC

. Behavioral Risk Factor Surveillance System: Prevalence and Trend Data–Overweight and Obesity, U.S. Obesity Trends, Trends by State 2010. Available online at http://www.cdc.gov/

brfss

/ Slide3

The Obesity PandemicSlide4

…In the United States

More

than one-third of adults and one-sixth of children and adolescents are obese.

This is more than double the prevalence in 1994. Slide5

The Future

Childhood obesity,

in the past 30

years, has

more than

doubled in children

and quadrupled in adolescents Obese Children who are 70 percent more likely to continue being obese into adulthood. Slide6

“Early

Adiposity

rebound”

BMI for

children

Even worse, being affected by childhood obesity at a

young age are predisposed to obesity and severe

obesity in adulthood.Slide7

Obesity impact in ElderlySlide8

Obesity & MortalitySlide9

Obesity & CancerSlide10

Obesity Disease

ICD 278.00Slide11

Obesity Disease

In

2000, a National

Institutes of

Health panel was one of the first to describe obesity as

a chronic disease

.More recently, the AMA adopted a policy in June 2013 recognizing obesity as a disease, “with the hope that doing so will help change how the medical community tackles

this complex issue.”Slide12

Obesity is a multifactorial disease that results from a combination of both physiological, genetic, and environmental inputs.Slide13
Slide14

“sick fat”

Adipose tissue has no less

pathogenic potential

than other body organs, with

adiposopathy

being analogous to cardiomyopathy, myopathy, neuropathy…

Adiposopathy or “sick fat” is defined as adipocyte/adipose tissue dysfunction caused by positive caloric balance and sedentary lifestyle in genetically and environmentally susceptible individuals.This results in adverse endocrine and immune responses that both directly and indirectly contribute to metabolic disease

and increased

CVD risk

.Slide15

Fat “storage”

Visceral adipose tissue (VAT) may be more metabolically active than subcutaneous adipose tissue (SAT).

These depots

(VAT)

inherently differ in processes involving lipolysis/

lipogenesis

, expression of adipocyte receptors, and differ in the secretion of adipokines/cytokines, enzymes, hormones, immune molecules…Slide16

From a clinician

standpoint, recognizing the pathogenic potential of adipose tissue may give a clearer rationale toward recommending weight reduction to overweight/obese patients. Slide17

E = mc2

Some obese

patients

believe that their metabolic fate is unavoidable, irrespective of intervention, and come to develop the defeatist belief that they will always gain fat mass, even if they reduce consumption of calories/energy. Slide18

Let’s be reasonable, Slide19

The brain!

The

brain is the central location of behavior and hunger, and the

hypothalamus

is a target for weight management pharmacotherapies.Slide20

Lessons…Slide21

New anti-Obesity drugs

H

it the market in the past 3 years:

lorcaserin

(

Belviq

)phentermine/topiramate (Qsymia)

naltrexone

/

bupropion

(

Contrave

)

liraglutide (Saxenda)Slide22

New Guidelines

Headed by the Endocrine Society with support from the Obesity Society and the European Society of Endocrinology.

The new guidelines expand on ones for managing overweight and obesity in adults that were released in 2013 by the Obesity Society, the American Heart Association, and the American College of Cardiology.Slide23

Classic Guidelines

USPSTF: “physicians should

offer or refer

their patients with obesity for high-intensity multicomponent behavioral interventions”

For patients who do not meet their target weight, intensification of therapy is needed.

Options

include: additional behavioral therapy; modifying dietary protocols; referral dietitian; the addition of pharmacotherapy that promotes weight loss; referral for bariatric surgery.Slide24

Natural History of Wt Loss Programs

With the

best of lifestyle interventions, the average weight

loss, was

5

%-10%

in 6 months.Not all patients are successful in achieving even 5% WL due to compensatory mechanisms

in

appetite and

metabolic rate

.

Furthermore

, the usual pattern after 6 months is a period

of weight stabilization (plateau)

; or

weight regain

gradually in

many patients

.

the Look AHEAD studySlide25

Goals of Treatment

Indeed, in clinical studies of

approved medications,

substantially more patients are

able to

achieve 5% to 10%, or even 15% weight loss

compared with placebo.In practice, the weight loss goal for a patient is approximately 5% to 15%.

If

achieved and maintained

,

these modest and moderate weight loss targets

are well

known to improve health

indices.Slide26

Impact of weight loss

Bariatric surgical procedures produce weight loss

by restricting

the size of a meal (all procedures) and by

their effects

on gut hormones that affect appetite, such as

gastric bypass and gastric sleeve. These procedures have been shown to not only produce weight loss, but to have a positive impact on diabetes, hypertension, dyslipidemia and even mortality.Slide27
Slide28

Current “Combination Rationale”

Because combination pharmacotherapy for obesity deploys medications with differing

mechanisms of action

, it offers the prospect of overcoming the counter-regulatory mechanisms that become manifest in the weight-reduced state.

Combination therapy also allows prescription of

lower doses

of each medication to minimize adverse effectsSlide29

Rationale for using medications

Prescription medications serve

as an adjunct

to

lifestyle changes

in order to produce the negative energy

balance that is required for weight loss. Medication does not work on its own—however, it does suppress the appetite

to help

the patient

ingest fewer calories.

With

less hunger

,

more satiety, and

the ability to

resist food cues

induced by medications

that act

on

central appetite centers

, patients will be

better

able

to adhere

to their diet.Slide30

“Obesity Based Medicine”

While

a wide variety of medications have

been utilized

to promote weight loss, only those shown to be

effective and

approved by the FDA for chronic obesity management should be utilized.Slide31

Obesity “Chronic Condition”

long-term use of medication for weight loss is most effective when continued indefinitely.

The

patient should be monitored

periodically.

Address patient concerns, and provide

ongoing support….(most important) Slide32

… and lifestyle

Medications are best suited for patients who are motivated to lose weight and adherent to lifestyle intervention since the combination is more effective than lifestyle intervention or pharmacotherapy alone.Slide33

PHARMACOTHERAPY CRITERIA

(

BMI) ≥

30

or

≥27

who have other risk factors or diseases, (comorbidities) such as hypertension, dyslipidemia, cardiovascular disease, diabetes, fatty liver disease, and obstructive sleep apnea... Slide34

Two Drugs for Weight Loss

In 2012, the FDA approved one new drug and a new combination of 2 old drugs as adjuncts to lifestyle changes for chronic weight management. Slide35

Qsymia

Qsymia

is a fixed-dose combination

P

hentermine and

Topiramate(ER). Slide36

Qsymia

(CONQUER): a

randomised

, placebo-controlled, phase 3 trial.

Interpretation:

The combination of

phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors.

JAMA.

2013;310(6):637-638. Slide37

Qsymia

The most commonly observed adverse

events:

dry mouth

constipation

paresthesia

dysgeusiaSlide38

Qsymia

Dose:

dose escalation

required

Target:

Phentermine/

Topiramate(ER) 7.5mg/46mgSlide39

Belviq

Belviq

(

Lorcaserin

) is a selective serotonin (5HT) 2C receptor agonist.Slide40

Belviq

The

BLOOM, BLOSSOM,

and

BLOOM-DM trials involved 7,648

overweight or obese patients.

In the BLOOM-DM trial, which included only patients with diabetes, lorcaserin 10 mg once or twice daily led to significant improvement in the glycated hemoglobin (HbA1c) compared with placebo (-1.0% vs -0.9% vs -0.4%, respectively;

P <.001 for both doses

of

lorcaserin

vs placebo).

Obesity.2012 Jul;20(7):1426-36. Slide41

Belviq

Lorcaserin

has been shown to have a favorable

tolerability profile

. Most common:

headache, nausea, dizziness, back pain and fatigue. Slide42

Belviq

10 mg twice daily, the dose approved by the FDASlide43

Belviq (safety)

Across the 3 trials, new

heart

valvulopathy

occurred in 2.37% of

lorcaserin patients and 2.04% of placebo patients (risk ratio, 1.16; 95% confidence interval, -0.46 to 1.13). Remember: cardiac 5HT‐2B receptors (Fenfluramine

in

Phen

-Fen

) produces

valvular

heart disease

not 5HT‐2C (Belviq)

One

concern is the use of

lorcaserin

with

other serotonergic drugs since there is a

possible risk

of

serotonin syndrome

.

For

e

xample SSRIs

…

Slide44

Contrave

Approved by FDA in September 2014 for obesity

.

Bupropion

SR/Naltrexone SR Slide45

Food!Slide46

Contrave

The combination of

naltrexone SR and bupropion SR simultaneously

stimulates hypothalamic

anorexigenic

(

satiety) neurons and blocks orexogenic (hunger) ones.Plus, this combination also has the potential to modulate

the mesolimbic

reward

system and regulate

dopamine

midbrain areas

to reduce food intake.Slide47

Contrave

Primarily

because of adverse events, the

completion rate

was low in

phase III trials with rates ranging from 54- 58%Slide48

Contrave

Adverse

events included

:

N

ausea

, headache, constipation, dizziness, vomiting, dry mouth, tremor, abdominal pain, bronchitis, and tinnitus. Slide49

Saxenda

L

iraglutide

3 mg (Saxenda®)

FDA approved December 23rd, 2014Also, “First New Anti-Obesity Drug in Canada in Two Decades”Slide50

GLP-1

Glucagon-like peptide receptor (GLP-1R) agonists

mimic

GLP-1, an

incretin

gut hormone secreted when a meal is ingested. GLP-1 lowers glucose by increasing insulin output and decreasing glucagon secretion, both in a glucose-dependent

manner (no hypogylcemia) GLP-1Rs are expressed in the periphery and in several areas in the brain that are implicated in the regulation of appetite. Slide51

Saxenda

Liraglutide

demonstrated

significant dose-dependent weight loss

in studies

of patients with type 2 diabetes mellitus (T2DM) and has led to its investigation and recent submission to the FDA for approval for the treatment of obesity.Slide52

Saxenda

A phase III study randomized patients with obesity

but

without

DM.

Over the 56 weeks of treatment, patients treated with liraglutide lost significantly more weight, and significantly more

liraglutide

-treated patients

lost

and

maintained

≥5% or ≥10% of randomization weightSlide53

“the more the better”

dose,

Liraglutide

1.2, 1.8, 2.4,

3.0

mgSlide54

Saxenda

The most frequent drug-related

adverse events

were mild to moderate, transient

nausea

and vomiting.

“desirable nausea”Slide55

Childhood ObesitySlide56

Orlistat

Orlistat

(

Xenical

, Alli) with lifestyle intervention, such as

a low-fat diet calorie-reduced diet, resulted in weight loss long term.Orlistat is also associated with reductions in low-density lipoprotein cholesterol (LDL-C)

The safety profile of

orlistat

is good. It is the only

obesity medication

approved for use in adolescents

Available both

by prescription (120 mg 3 times daily) and OTC (60 mg)However

,

gastrointestinal adverse

events (oily spotting, flatulence, and fecal

urgency) limit

patient acceptance, although these symptoms

are generally

mild and

transient (again, diet compliance..)

Kidney

stones may occur

in patients

at risk for renal insufficiency and in rare cases

serious liver

injury have been reported with

orlistat

.

Remember to supplement with vitamins.Slide57

Opening the Door…Slide58

Context

Barriers to Discussing Weight by

Health Care

Providers:

◦ Concern over offending patient

◦ Belief that patients are not motivated to

make changes and that counseling will be ineffective◦ Time◦ Payment◦ Lack of knowledge and skills

◦

Lack of practical toolsSlide59

Primary care literature

“I’m afraid raising the issue of weight will offend my patient.”

“What difference could my counseling efforts make anyway? My patients won’t follow my recommendations and won’t lose weight?”

“I don’t have the time.”

“I don’t get paid for obesity counseling.”

“I’m not sure how to do this.”

“I don’t’ have practical tools with which to do this.”

Slide60

Scenario

“No

health care provider

has ever

discussed weight with

patient before

and he/she is in your office…”Slide61

Raising the Issue of Weight

Language

.

Preferred

term is

“weight

”“Achieving and/or maintaining a healthy weight”Least desirable term is “fat” or “fatness”

The term “obesity

”

could

be avoided

.

Permission.

An example:“Evelyn

, now that we’ve addressed your main reason for the visit, I’d like to discuss the issue of weight. Would that be ok with

you

?”Slide62

5As Paradigm

Ask

(or Assess)

Advise

Agree

Assist ArrangeSlide63

ASK

How

ready are you to lose weight?

“Would you be interested in working together on helping you make changes in your lifestyle over a period of time which would help you achieve a healthier weight

?”

What

do you believe you could do to get to a healthier weight?Slide64

Assessing Readiness to Change

How

ready are you to lose weight?

I have not really thought about it (

pre-contemplation)

I mean to lose weight but I don’t actually get around to it. (contemplation) From time to time, I go on a diet/exercise, but then I stop after a few days (preparation)

I have been working on losing weight for the past

6 months

(

action

)

I have kept my weight off for over 6 months (maintenance)

Readiness to change (Huang J et al, 2004)Slide65

ASK

“

Would you be interested in working together on helping you make changes in your lifestyle over a period of time which would help you achieve a healthier weight?”Slide66

Asking/Assessing

Motivation…

“What do you

believe

you could do to get to a healthier weight

?”

The moment of truth…“what are the main reasons you would like to lose weight, and why now?”Slide67

ADVISE

An

“opportunity” to advise about impact of behaviors on weight and health.Slide68

Calories??

Bottom Line

•

It’s the calories and all calories count

•

Goal is a 500 -750 k/cal/day energy deficit

Prescribe 1200-1500 k/cal/day range (low calorie diet)Slide69

Exercise

“Exercise and diet go together. Weight management is most successful when careful attention is given to both physical activity and proper nutrition.”

American College of Sports Medicine, 2013

• Physical Activity:

The Look AHEAD Study

– unsupervised– 175 minutes moderate intensity/week– 5 days/week– walking!!!Slide70

AGREE

“

Negotiating”

framework: SMART goals

S – specificM – measurableA – achievable

R

–

rewarding

T

–

in what time periodSlide71

Assist & Arrange

Assistance

◦

O

besity

tx…

◦ Recommending supportive apps/programs…◦ Warn about what doesn’t work: commercial wt

loss…Slide72

Arrange

Follow-up

appropriately.

Reinforcement.

Support

- most important!Slide73

Thank you