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Multifaceted Approaches to Optimize Care for Patients with Obesity

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Facilitating Changes in

Behavior – Meeting the Needs

of Patients and Providers

Robert F. Kushner, MD

Professor of Medicine, Feinberg School of Medicine

Director, Center for Lifestyle Medicine, Northwestern Medicine

Chicago, IL



Lifestyle Counseling Rates Among PCPs

NAMCS (n=32,519 records)

0

10

20

30

40

50

60

Hypertension Diabetes Obesity All Adults

1995-1996

2007-2008

Pe

rce

nta

ge

NAMCS = National Ambulatory Medical Care SurveyKraschnewski JL, et al. Med Care. 2013;51(2):186-192.

Percent of Patients Receiving PCP

Advice by Obesity Classification

Simkin-Silverman LR, et al. Prev Med. 2005;40(1):71-82.

3228

46 4848

62

75

84

0

10

20

30

40

50

60

70

80

90

100

Overweight Obesity I Obesity II Obesity III

Specific Advice Told Overweight

(BMI 27.0 to 29.9) (BMI 30.0 to 34.9) (BMI 35.0 to 39.9) (BMI ≥ 40.0)

Told Overweight: ᵪ2 (test for linear trend) – 16.5, P – .001

Gave Weight Loss Advice: ᵪ2 (test for linear trend) – 5.5, P – .019

Pe

rce

nta

ge

Mr. Smith, you are a 52-year-old man with

hypertension, prediabetes, and GERD.

I can treat these problems. If you were

able to lose some weight that would

help too.

Traditional Medical Model



Current Hierarchical Provision of Obesity Care

by HCPs – Obesity as a ‘Secondary Issue’

Don’t Ask: Don’t Tell

Identify & Give Advice

“Lose Weight”

Assess & Refer

Counsel & Treat

Specialist

HCP = health care provider

Weight Management is Embedded

within the Office Visit

• Embeddedness = observed tendency

among health care providers to see weight

as an issue within other types of medical

visits rather than presenting as a discreet

issue

Asselin J, et al. Clin Obes. 2015 Aug 25. [Epub ahead of print]

Mr. Smith, you are a 52-year-old man who is

overweight. Medically, we call this obesity. You now

have developed hypertension, prediabetes, and

GERD, all complications of obesity. Unless we

focus on your weight, you are at risk of developing

many more medical problems. What do you think?

A Paradigm Shift



Proposed Hierarchical Provision of Obesity

Care by HCPs – Obesity as a ‘Primary Issue’

Identify, Assess, & Refer

Counsel & Treat

Specialist

HCP = health care provider

Practice Issues (Barriers)

Functioning in an acute care model

Limitation of time

Few available resources

Inadequate reimbursement

Lack of effective teamwork

Insufficient training

Bias

What are the Barriers?

Closing the Obesity Gap

Importance Provision of Care

Gap in

Training

& Practice



Developing Professional

Competence

• “The habitual and judicious use of

communication, knowledge, technical skills,

clinical reasoning, emotions, values, and

reflection in daily practice for the benefit of the

individual and community being served.”

• “Competence builds on a foundation of basic

clinical skills, scientific knowledge, and moral

development.”

Epstein RM, et al. JAMA. 2002;287(2):226-235.

Patient-Physician Communication

Adapted from: Rotor D. Patient Ed and Counseling, 2000.

Patient Power/

Interest

Physician Power/Interest

High

High

Low

Low

Mutuality“Shared decision-making”

Paternalism

“Do what I say!”

Consumerism“What ever you want”

Dysfunctional“Don’t ask: Don’t tell”

The 5 A’s Counseling Framework

Vallis M, et al. Can Fam Physician. 2013;59(1):27-31.

Sherson EA, et al. Fam Pract. 2014;31(4):389-398.

USPSTF Adaptation for

Obesity

Assess Ask

Advise Assess

Agree Advise

Assist Agree

Arrange Assist



The 5 A’s Counseling Framework

Ask/Assess • Weight history

• Contributions to weight gain

• Past treatment attempts

• Diet and physical activity patterns

• Physical examination and pertinent laboratory tests

Advise • Perception of health problems associated with excess

weight

• Explain complications of excess weight

• Explain benefit of weight loss to improve health

• Explore treatment options

• Provide strategies for weight management

Agree • Decide upon a collaborative-based treatment plan

Assist • Discuss potential barriers to implement treatment plan

• Provide handouts

Arrange • Discuss follow up plans and/or referrals

Motivational Interviewing (MI)

• Motivational interviewing is a collaborative,

goal-oriented approach of communication

to elicit behavior change in patients.

• The approach is designed to identify and

resolve ambivalence toward a specific goal

by connecting necessary changes to

incentives that reduce barriers for change.

Motivational Interviewing. 2nd Ed, Miller WR and Rollnick S, eds. The Guilford Press, New York, 2002.

Motivational Interviewing Skills

• Ask– Ask open-ended questions inviting the patient to

consider how and why they might change.

• Listen

– Understand the patient’s experience and summarize with reflective listening.

• Inform– Ask permission to provide information, then ask

what the implications might be for the patient.

Rollnick S, et al. BMJ. 2010;340:c1900.



Moving to a New Paradigm

in Obesity Care

Adapted from: Tsai AG, et al. J Gen Intern Med. 2009;24(9):1073-1079; Carvajal R, et al. Ann N Y Acad Sci. 2013;1281:191-206.

Assess and treat obesity-related

co-morbid conditions

Assess motivation for weight

management

HCP provides

weight

management

HCP referral for

weight

management

HCP and

colleagues offer

collaborative care

HCP referral to

obesity medicine

specialist

LM counseling,

(pharmacotherapy)

Commercial or

web-based, RD,

disease

management

(NP, PA, RN, RD,

PsyD, coaches),

LM counseling,

pharmacotherapy

Team approach,

LM counseling,

VLCD,

pharmacotherapy,

bariatric surgery

Shared decision-

making (SDM)

• Requires competency in and a thorough understanding of the

treatment of obesity and the genetic, biologic, environmental, social,

and behavioral factors that contribute to obesity.

• Employs therapeutic interventions including diet, physical activity,

behavioral change, and pharmacotherapy.

• Utilizes a comprehensive approach, and such as nutritionists,

exercise physiologists, psychologists and bariatric surgeons as

indicated to achieve optimal results.

• Maintains competency in providing pre-, peri-, and post-surgical care

of bariatric surgery patients, promotes the prevention of obesity, and

advocates for those who suffer from obesity.

American Board of Obesity Medicine: www.abom.org.

Conclusion

• Obesity care is currently embedded within the office visit.

• Making obesity a primary concern will require increased competency in obesity care along with changes in the medical practice system.

• Use of the 5 A’s counseling framework and motivational interviewing (MI) is intended to facilitate behavior change.

http://www.abom.org/



Achieving a Comfort Zone

with Pharmacotherapy

Scott Kahan, MD, MPH, FTOSDirector, National Center for Weight and Wellness

Medical Director, Strategies To Overcome and Prevent

(STOP) Obesity Alliance

George Washington University

Washington, DC

[email protected]

Obesity Is Significantly

Under-Treated

0

25

50

75

100

Hypertension Diabetes Depression Obesity

Affected

Treated (Medication)

# o

f P

atie

nts

(Millio

ns)

Xia Y, et al. Obesity. 2015;23(8):1721-28.



FDA-Approved Obesity

Pharmacotherapy Options

• Phentermine (and other noradrenergic agents)

• Orlistat

• Lorcaserin

• Phentermine / topiramate ER

• Naltrexone SR / bupropion SR

• Liraglutide 3.0 mg

Indications: Adjunct to behavioral modification in

BMI >30 kg/m2 or 27-30 kg/m2 with comorbidities

Phentermine

• Sympathomimetic amine

• Approved 1959

• Short-term use; schedule IV

• Dosing: 15-37.5mg qAM

• Contraindications/warnings:

Pregnancy, nursing, MAOI

use, glaucoma, drug abuse

history, hyperthyroidism,

uncontrolled hypertension,

tachycardia, history of CAD,

CHF, stroke

• Lipase inhibitor

• Approved 1999

• Long-term use; not scheduled

• 120 mg TID with meals (Rx) or

60 mg TID (OTC)

• Use MVI with fat-soluble

vitamins at bedtime

• Contraindications: pregnancy,

chronic malabsorption

syndrome, cholestasis

• Gastrointestinal AEs

Phentermine [package insert]. Cranford, NJ: Alpex Pharma SA: 2011. Orlistat [package insert]. South San Francisco,

CA: Genentech: 2012; Orlistat [package insert]. Moon Township, PA: GlaxoSmithKline: 2011.

Orlistat

Lorcaserin

• Selective 5HT-2c receptor agonist

• Increases satiety

• Approved in 2012

• Long-term use; schedule IV

• Single dose: 10 mg BID;

discontinue if <5% BWL after 12

weeks

• Contraindications: pregnancy

• Warnings: coadministration with

serotonergic agents; valvular heart

disease; psychiatric disorders,

priapism

Belviq [Prescribing Information]. Woodcliff Lake, NJ: Eisai Inc; 2012. Fidler MC, et al. J Clin Endocrinol Metab.

2011;96:3067. Smith SR, et al. N Engl J Med. 2010;363(3):245. Smith SR, et al. Obesity. 2014: 22:2137-46. Reprinted with

permission.



Lorcaserin: Weight Change over 2 Years

Smith SR, et al. N Engl J Med. 2010;363:245-256. Reprinted with permission.

Lorcaserin: Weight Change over 2 Years

Smith SR, et al. N Engl J Med. 2010;363:245-256. Reprinted with permission.

Endpoint Lorcaserin Placebo P

Waist circumference

(cm)

−6.8 −3.9 <0.001

SBP/DBP (mm Hg) −1.4/−1.1 −0.8/−0.6 0.04/0.01

Cholesterol (% Δ)

Total

LDL

HDL

−0.90

2.87

0.05

0.57

4.03

−0.21

0.001

0.049

0.72

Triglycerides (%) −6.15 −0.14 <0.001

A1c -0.9 -0.4 <0.001

Heart rate (bpm) −2.0 −1.6 0.049

Beck depression II −1.1 −0.9 0.26

Key Secondary Endpoints

Smith SR, et al. NEJM. 2010;363:245-256. O’Neil PM, et al. Obesity. 2012;20:1426-1436.



N (%) Lorcaserin

(N = 3195)

Placebo

(N = 3185)

Headache 537 (16.8) 321 (10.1)

Dizziness 270 (8.5) 122 (3.8)

Nausea 264 (8.3) 170 (5.3)

Constipation 186 (5.8) 125 (3.9)

Fatigue 229 (7.2) 114 (3.6)

Dry mouth 169 (5.3) 74 (2.3)

Lorcaserin: Adverse Events Reported

by 5% or More in Any Group

Smith SR, et al. N Engl J Med. 2010;363:245-256. O’Neil PM, et al. Obesity. 2012;20:1426-1436.

• Phentermine: blunts appetite

• Topiramate: prolongs satiety

• Approved in 2012

• Long-term use; schedule IV

• 4 fixed doses (3.75/23mg

increments)

• Titrate if <3% weight loss at 12 wk

• REMS: teratogenicity


glaucoma, MAOIs, hyperthyroidism

Phentermine and topiramate extended-release [package insert]. Mountain View, CA: Vivus; 2012.

Garvey WT, et al. Am J Clin Nutr. 2012;95(2):297-308.Reprinted with permission.

Phentermine / Topiramate ER


Prevents Progression to T2DM

3.7%

1.7%

0.9%

0

0.5

1

1.5

2

2.5

3

3.5

4

Placebo Phen/TPM ER 7.5/46 mg Phen/TPM ER 15/92 mg

Pro

gre

ss

ors

pe

r y

ea

r (%

)

Garvey WT, et al. Am J Clin Nutr. 2012;95:297-308.

76%

54%

Annualized Incidence of T2DM



Patients with Extreme Obesity (BMI >45)

Kahan S, et al. Poster: The Obesity Society, Nov 2015.

22.4

8.6

3.5 3.5

64.1

30.8

10.3

5.1

83.1

69

50.7

28.2

0

10

20

30

40

50

60

70

80

90

Weight loss of ≥5% Weight loss of ≥10% Weight loss of ≥15% Weight loss of ≥20%

Placebo Phentermine / Topiramate ER 3.75/23 (n=39)

Phentermine / Topiramate ER 15/92 (n=71)

**

**

**

**

**

*

*

* P ≤ .01 vs. placebo

** P ≤ .001 vs. placebo

Phentermine/Topiramate ER: Adverse Reactions

Leading to Treatment Discontinuation

Placebo

(n=1561), %

Phentermine/

Topiramate ER

3.75 mg/23 mg

(n=240), %

Phentermine/

Topiramate ER

7.5 mg/46 mg

(n=498), %

Phentermine/

Topiramate ER

15 mg/92 mg

(n=1580), %

Vision blurred 0.5 2.1 0.8 0.7

Headache 0.6 1.7 0.2 0.8

Irritability 0.1 0.8 0.8 1.1

Dizziness 0.2 0.4 1.2 0.8

Paraesthesia 0.0 0.4 1.0 1.1

Insomnia 0.4 0.0 0.4 1.6

Depression 0.2 0.0 0.8 1.3

Anxiety 0.3 0.0 0.2 1.1

Qsymia (phentermine and topiramate) capsules [package insert]. Mountain View, CA: Vivus; 2014.

Billes SK, et al. Pharm Res. 2014;84:1-11.

β-endorphin

α-MSH

-

+MC4 receptor

μ-opioid receptor

Naltrexone SR / Bupropion SR:

Mechanism of Action



Naltrexone SR / Bupropion SR

• Bupropion: Dopamine/norepinephrine

reuptake inhibitor

• Naltrexone: opioid receptor antagonist

• Approved 2014

• Long-term use; not controlled

• Dosing (8 mg / 90 mg tabs): titrate

weekly to 2 BID

• Consider discontinuation if <5%

weight loss after 12 weeks


seizures, uncontrolled HTN, chronic

opioid use, MAOI use

Contrave prescribing information. Takeda Pharmaceuticals. Greenway, et al. Obesity. 2009;17:30-39. Billes, et al. Pharm

Res. 2014; 84;1-11.

-8.1 -8.2

-11.5

-5.9

-1.8-1.4

-7.3

-2.2

-14

-12

-10

-8

-6

-4

-2

0

Naltrexone / Bupropion Placebo

Naltrexone SR / Bupropion SR :

Patients Completing 1 Year of Treatment

Wadden TA, et al. Obesity. 2011;19:110-20. Hollander P, et al. Diab Care. 2013;36(12):4022-9. Greenway, et al. Obesity.

2009;17:30-39. Apovian CM, et al. Obesity. 2013;21(5):935-43. Billes, et al. Pharm Res. 2014; 84;1-11.

COR-I COR-II COR-BMOD COR-DR

% W

eig

ht ch

an

ge

Naltrexone SR/bupropion SR 32/360 mg Placebo

Nausea 32.5% 6.7%

Constipation 19.2% 7.2%

Headache 17.6% 10.4%

Vomiting 10.7% 2.9%

Dizziness 9.9% 3.4%

Insomnia 9.2% 5.9%

Dry mouth 8.1% 2.3%

Subjects discontinuing due to AE:

Overall 24% 12%

Nausea 6.3%

Headache 1.7%

Vomiting 1.1%

Contrave (naltrexone HCL and bupropion HCL) extended-release tablets [package insert]. Deerfield, IL and La Jolla, CA:

Takeda / Orexigen; 2014.




Liraglutide 3.0 mg

• GLP-1 receptor agonist

• Multiple actions; effect on weight is

primarily via POMC neurons

• Liraglutide 1.8 mg: type 2 diabetes

• Liraglutide 3.0 mg: obesity treatment

• Long-term use; not controlled

• Dosing: SC; titrate weekly by 0.6 mg

• Discontinue if <4% loss at 16 weeks

• REMS: medullary thyroid carcinoma,

acute pancreatitis

Saxenda (liraglutide) injection [package insert]. Plainsboro, NJ: Novo Nordisk; 2014; Pi-Sunyer X, et al. NEJM. 2015.

Reprinted with permission.

63.2

33.1

14.4

27.1

10.63.5

0

10

20

30

40

50

60

70

≥ 5% ≥ 10% ≥ 15%

Liraglutide Placebo

P<0.001

P<0.001

P<0.001

Pa

tie

nts

(%

)

Liraglutide 3.0 mg for Weight

Maintenance

Data submitted to FDA Endocrinologic and Metabolic Drug Advisory Committee, NDA 206-321, September 11, 2014.

Liraglutide 3.0 mg

% Liraglutide 3.0 mg Placebo Discontinuation

Nausea 39 14 2.9

Diarrhea 21 10 1.4

Vomiting 16 4 1.7

Constipation 19 8

Dyspepsia 9 3

Abdominal pain 5 3

Hypoglycemia in T2DM 23 13

Headache 14 13

Dizziness 7 5

Fatigue 7 4

Increased lipase 5 2

Overall discontinuation: 9.8% vs 4.3%

Saxenda (liraglutide) injection [package insert]. Plainsboro, NJ: Novo Nordisk; 2014.



Combination Therapy

Adapted from Wadden, et al. NEJM. 2005.

Medication alone

Lifestyle modification alone

Medication + brief therapy

Combined therapy

Placebo alone

Thank you

Scott Kahan, MD, MPH

[email protected]



Getting Back to the Basics –

Patient Selection for

Pharmacotherapy

Ken Fujioka, MD

Director of Nutrition and Metabolic Research

Scripps Clinic Dept. of Endocrine

Addressing Individual Patient Needs

and Preferences

• Treat obesity like any disease and work it up like a disease

• History– cause of obesity

Portion control, snacking, binge, low activity level, Craving of specific foods etc.

– comorbid diseases

– current meds

– patient expectations – on weight loss

– personal profile – wants to get pregnant?

Physical

• General: is the patient depressed

• BMI: is it over 35 kg/m2 with a co-morbidity

• Waist circumference

• Thyroid exam - nodule?

• Cardiac – Heart rate and blood pressure



Treatment Plan

• Medications

– Diabetic meds with weight loss

GLP-1 receptor agonists, SGLT-2 inhibitors

– Weight loss medications

Lorcaserin, Phentermine / Topiramate ER,

Naltrexone SR / Bupropion SR, Liraglutide 3.0 mg

• Bariatric Surgery

– Sleeve gastrectomy vs bypass

• Failed bariatric surgery

– Conversion to bypass

– Add weight loss medications

• Everyone gets Diet and Lifestyle modification

Lorcaserin

Mechanism

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

Apovian CM, Aronne LJ, Bessesen DH. J Clin Endocrinol Metab. 2015;100: 342–362



Mechanism



Discontinuation Rates

Due to Drug AEs

• Placebo – 6.7%

• Lorcaserin – 8.6%

– Headache – 1.3% vs 0.8%

– Depression – 0.9% vs 0.5%

– Dizziness – 0.7% vs. 0.2%

Lorcaserin (Prescribing Information) Woodcliff Lake, NJ Eisai Inc. 2012

Clinical Practice Pearls

• This is a safe drug with no stimulating effects

– Can be considered in the Cardiovascular patient #

• If you have a patient on SSRIs or other

serotonin medications then use with caution

• Hypoglycemia a risk in diabetic patients on

sulfonylureas and insulin

• The patient with portion control issues or

Satiety

# Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline





Mechanism



Mechanism





Topiramate

• Very potent weight loss agent

– Positive studies in Binge Eating

• Significant number of potential Adverse Events

– REMS program: potential for teratogenicity, cleft lip and cleft

palate

Increased heart rate

Suicide and mood and sleep disorders

Acute myopia and glaucoma

Cognitive impairment

Metabolic acidosis

Creatinine elevations

Phentermine / Topiramate ER:

EQUIP and CONQUERMost Commonly Reported Treatment Emergent Adverse Events


Adverse Event (%)

(N=3749)Placebo

PHEN/TPM ER

3.75/23

PHEN/TPM ER

7.5/46

PHEN/TPM ER

15/92

Paresthesia 1.9 4.2 13.7 19.9

Dry mouth 2.8 6.7 13.5 19.1

Constipation 6.1 7.9 15.1 16.1

Upper respiratory tract

infection12.8 15.8 12.2 13.5

Headache 9.3 10.4 7.0 10.6

Dysgeusia 1.1 1.3 7.4 9.4

Nasopharyngitis 8.0 12.5 10.6 9.4

Insomnia 4.7 5.0 5.8 9.4

Dizziness 3.4 2.9 7.2 8.6

Sinusitis 6.3 7.5 6.8 7.8

Nausea 4.4 5.8 3.6 7.2

Back pain 5.1 5.4 5.6 6.6

Fatigue 4.3 5.0 4.4 5.9

Blurred vision 3.5 6.3 4.0 5.4

Diarrhea 4.9 5.0 6.4 5.6

Phentermine / Topiramate ER:

EQUIP and CONQUERMost Commonly Reported Treatment Emergent Adverse Events


Adverse Event (%)

(N=3749)Placebo

PHEN/TPM ER

3.75/23

PHEN/TPM ER

7.5/46

PHEN/TPM ER

15/92

Paresthesia 1.9 4.2 13.7 19.9

Dry mouth 2.8 6.7 13.5 19.1

Constipation 6.1 7.9 15.1 16.1

Upper respiratory tract

infection12.8 15.8 12.2 13.5

Headache 9.3 10.4 7.0 10.6

Dysgeusia 1.1 1.3 7.4 9.4

Nasopharyngitis 8.0 12.5 10.6 9.4

Insomnia 4.7 5.0 5.8 9.4

Dizziness 3.4 2.9 7.2 8.6

Sinusitis 6.3 7.5 6.8 7.8

Nausea 4.4 5.8 3.6 7.2

Back pain 5.1 5.4 5.6 6.6

Fatigue 4.3 5.0 4.4 5.9

Blurred vision 3.5 6.3 4.0 5.4

Diarrhea 4.9 5.0 6.4 5.6



Clinical Pearls and


• Balance of excellent weight loss with the potential for more

clinical adverse events

• In the pivotal trials they did allow pts on SSRIs to be in the

study

• Topiramate has positive data in binge eating

• Despite the fact that this medication contains a

sympathomimetic it did not typically increase blood pressure

but does increase pulse

– Not recommended for known cardiovascular patients

• Recommend the middle 7.5 / 46 mg dose

– Weight loss at 2 years very similar to highest dose

– If the pt needs to stop they do not have to taper down


Mechanism





Mechanism



COR-1: Change in Selected Items from the

Control of Eating Questionnaire at Week 56

Greenway FL, Fujioka K, Plodkowsky R, et al. Lancet. 2010;376, 595-605.

*P <.05 vs placebo.

How hungry have you felt?

How full have you felt?

How difficult has it been

to control your eating?

How difficult has it been

to resist any food cravings?

How often have you eaten

in response to food cravings

How often have you had

food cravings for starchy foods?

-20 -15 -10 -5 0 -5

Less Change from baseline (mm) More

*

**

**

*

*

*

Placebo (n=511)

Naltrexone 16 mg plus

bupropion (n=471)

Naltrexone 32 mg plus

bupropion (n=471)

Adverse Events

• Nausea

– Forced Titration in studies

• Constipation

• Headache

• Vomiting

• Dizziness

• Insomnia

– Take second dose late afternoon

• Dry mouth

Table 3. Adverse Reactions Reported by Obese or Overweight Patients

With an Incidence (%) of at Least 2% Among Patients Treated with

Naltrexone SR / Bupropion SR and More Common than with Placebo




Drug-Drug and Other Interactions

• Ticlopidine and Clopidogrel (Plavix)

– Decrease dose to 1 BID

• Seizure risk with bupropion thus do not give

to patients with a seizure history

• 1 to 2 mm Hg rise in blood pressure and

pulse (check BP the first 12 weeks)

• Do not give to patient on chronic opioids

Clinical Pearls


• Bupropion a known anti-depressant thus useful in

the depressed patient

– Be cautious with combining with other depression

meds (potential for interaction)

• Has the potential to work on “Cravings” and food

reward type eating

• Recommend slow titration, (or back titration) and

may not need to go to the highest dose

• If patient has insomnia may need to take second

dose earlier in the day.

Liraglutide 3.0 mg



Mechanism



Mechanism



Liraglutide 3.0 mg Delayed Time

to Onset of T2DM

Time to onset of T2DM, Weibull analysis

Time to onset of T2DM over 3 years:

• 2.7 times longer

95% CI [1.9; 3.9] (p<0.0001)

Estimated hazard ratio at week 160

(liraglutide 3.0 mg/placebo):

• HR = 0.207 (p<0.0001)

• Risk reduction: 79.3%

Numbers needed to treat (NNT):

• 14 / 3 years88

90

92

94

96

98

100

0 16 32 48 64 80 96 112 128 144 160

γ=2.68

SPlacebo(60)

SLira(160)

Part

icip

an

ts n

ot

dia

gn

osed

with

T2

DM

(%

)

Week

Liraglutide 3.0 mg Placebo

The time of onset of T2DM occurs in between the first of the two required registrations of elevated HbA1c, FPG or 2-hour OGTT plasma glucose, and the diabetes

assessment visit prior to the first registration. The estimated survival time is based on an analysis of time to onset of T2DM analyzed in a Weibull model that includes

treatment, sex and baseline BMI stratum as fixed factors and baseline FPG value as covariate. BMI, body mass index; FAS, full analysis set; FPG, fasting plasma

glucose; HbA1c, glycosylated hemoglobin; HR, hazard ratio; NNT, number needed to treat; OGTT, oral glucose tolerance test; T2DM, type 2 diabetes mellitus

le Roux et al. Obesity Week 2015, 2–6 November 2015, Poster T-P-LB-3843



Subjects with Normoglycemia

Over Time

0

20

40

60

80

100

-1 28 56 80 104 128 152 160 172

Liraglutide 3.0 mg PlaceboOff drug follow up Off drug follow up

Pro

port

ion

of

part

icip

an

ts (

%)

Week

Full analysis set, last observation carried forward. Statistical analysis is logistic regression. Normoglycemia is defined as fasting plasma

glucose <100 mg/dL (<5.6 mmol/L) and/or 2-hour post-challenge glucose <140 mg/dL (<7.8 mmol/L) and/or HbA1c <5.7%

66%

36%

Odds ratio for normoglycemia at week 160

Liraglutide 3.0 mg/Placebo: 3.6

(95% CI [3.0; 4.4], p<0.0001)

71%

39%

69%

33%

70%

30%

le Roux et al. Obesity Week 2015, 2–6 November 2015, Poster T-P-LB-3843

Measured at OGTT visits: 0–172 weeks

Contraindications and Potential

Adverse Events

• Personal or family history of medullary

thyroid carcinoma

• Multiple Endocrine Neoplasia syndrome

type 2

• Gastro paresis

• Pancreatitis

• Increased heart rate (0.9% HR > 100)

Clinical Pearls: Liraglutide 3.0

• Part of the feedback pathway that regulates weight

and food intake: thus hitting multiple receptors for

appetite regulation (Satiety and time to next feeding)

• Non-stimulating and in this author’s opinion useful in

the cardiovascular patient

• Titrate slowly as GI side effects are common

– Don’t be afraid to back titrate

• May not need top dose to get effective weight loss

• Drug of choice in the pre-diabetic and diabetic

• Patient that has already lost some weight on their

own



Contraindications & Cautions

Clinical scenario Avoid/caution

Elevated seizure risk Naltrexone SR / bupropion SR

h/o recurrent kidney stones Phentermine / topiramate ER, orlistat

h/o glaucoma Phentermine / topiramate ER

Uncontrolled hypertension Naltrexone SR / bupropion SR

Coronary artery disease Phentermine

Moderate-severe renal

impairment

Do not exceed half-dose: Phentermine /

topiramate ER, naltrexone SR / bupropion SR

Caution: liraglutide 3.0 mg, lorcaserin

Moderate-severe hepatic

impairment

Do not exceed half-dose: Phentermine /

topiramate ER

Do not exceed ¼ dose: naltrexone SR /

bupropion SR

Caution: liraglutide 3.0 mg, lorcaserin

SSRI use Caution: lorcaserin

Dual Benefits

Obesity and… Consider, but not explicitly

approved…

Smoking Naltrexone SR / bupropion SR

Depression Naltrexone SR / bupropion SR

Migraines Phentermine / topiramate ER

Diabetes Liraglutide 3.0 mg

Chronic constipation Orlistat

Elevated LDL Orlistat

Choosing Between Options

• Contraindications

• Dual benefits

• Studied populations

Drug factors

• Patient preferences

• Adverse events

• Prior experiences

• Access

Patient factors

• Provider knowledge/comfort

Healthcare Provider factors

please note: activity presentations are (cme@vindicocme...

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