Sanford I. Weill Professor of Metabolic Research Weill ...syllabus.aace.com/2016/chapters/lower-new-york/presentations/5...Gaps Between 2015 Obesity Pharmacology ... her diet and increasing

What’s New in

Pharmacotherapy for ObesityLouis J. Aronne, MD, FACP, FTOS

Sanford I. Weill Professor of Metabolic ResearchWeill Medical College of Cornell University

Medical Director, Comprehensive Weight Control CenterDivision of Endocrinology, Diabetes, and Metabolism

New York, NY

DisclosuresOwnership Interest:BMIQCardiometabolic Support NetworkGelesisMyos CorporationZafgen, Inc.

Board of Directors:Myos CorporationJamieson Laboratories

I am a consultant, speaker, advisor, or receive research support from:Aspire Bariatrics

Eisai Inc.

Enteromedics

Gelesis

GI Dynamics

Novo Nordisk

Pfizer

VIVUS Inc.

Zafgen Inc.

As faculty of Weill Cornell Medical College, we are committed to providing transparency for any and all external relationships prior to giving an academic presentation.

Gaps Between 2015 Obesity Pharmacology Guidelines and Actual Practice

If a patient’s response is effective (weight loss >5% of body weight at 3 mo) and safe, we recommend it be continued

If ineffective (weight loss <5% at 3 mo) or there are safety or tolerability issues, we recommend it be discontinued

J Clin Endocrinol Metab. 2015 Feb;100(2):342‐62.Pharmacological management of obesity: an endocrine Society clinical practice guideline.

Guideline Recommendations

Just under half (46%) of adults in the U.S. fit the criteria for use of anti‐obesity pharmacotherapy, but only 2% receive such treatment 1,2

1. Samaranayake NR, et al. Ann Epidemiol. 2012 May;22(5):349‐ 53. 2. Xia Y, et al. Obesity (Silver Spring). 2015 Aug;23(8):1721‐8.

Actual Practice

Less than one percent (0.7%) of eligible overweight or obese patients (n=1,835,541) received pharmacotherapy for weight lossThose who received it tended to be:• Heavier (BMI 33.6 vs. 31.3 kg/m2)• Younger (42 vs. 52 years)• Female (84.3 vs. 58.2% male)• Commercially insured (70.1 vs. 50.4%) • Used more antidepressants (30.8 vs. 14.1%)• Used more NSAIDs (21.7 vs. 12.0%) Zhang S, et al. Obes Sci Pract. 2016;doi:10.1002/osp4.46.

4

Gaps Between 2015 Obesity Pharmacology Guidelines and Actual Practice

If a patient’s response is effective (weight loss >5% of body weight at 3 mo) and safe, we recommend it be continued

If ineffective (weight loss <5% at 3 mo) or there are safety or tolerability issues, we recommend it be discontinued

J Clin Endocrinol Metab. 2015 Feb;100(2):342‐62.Pharmacological management of obesity: an endocrine Society clinical practice guideline.

Guideline Recommendations

Just under half (46%) of adults in the U.S. fit the criteria for use of anti‐obesity pharmacotherapy, but only 2% receive such treatment 1,2

1. Samaranayake NR, et al. Ann Epidemiol. 2012 May;22(5):349‐ 53. 2. Xia Y, et al. Obesity (Silver Spring). 2015 Aug;23(8):1721‐8.

Actual Practice

Less than one percent (0.7%) of eligible overweight or obese patients (n=1,835,541) received pharmacotherapy for weight lossThose who received it tended to be:• Heavier (BMI 33.6 vs. 31.3 kg/m2)• Younger (42 vs. 52 years)• Female (84.3 vs. 58.2% male)• Commercially insured (70.1 vs. 50.4%) • Used more antidepressants (30.8 vs. 14.1%)• Used more NSAIDs (21.7 vs. 12.0%) Zhang S, et al. Obes Sci Pract. 2016;doi:10.1002/osp4.46.

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W E I L L . C O R N E L L . E D U

Pharmacotherapy Utilization: T2DM vs Obesity

Thomas, C et al Obesity (Silver Spring). 2016 Sep;24(9):1955-61. doi: 10.1002/oby.21533.:

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

Obesity Type 2 Diabetes

U.S

. Adu

lt Po

pula

tion

(%)

Adults in the U.S.

Indicated Treated

W E I L L . C O R N E L L . E D U

Uptake of SGLT 2s vs Ant i -Obesi ty Drugs

Title for Slide Deck 7

Prescriptions Dispensed, U.S., 2012-2015

74% Phentermine

18.6% new anti-obesity pharma

MARKETSHARE

• Thomas, C et al Obesity (Silver Spring). 2016 Sep;24(9):1955-61. doi: 10.1002/oby.21533.:

Prevalence of physicians, by medical specialty, prescribing phentermine, new anti‐obesity medications, and SGLTs U.S., 2012‐2015

Thomas CE, Mauer EA, Shukla AP, Rathi S, Aronne LJ.Obesity (Silver Spring). 2016 Sep;24(9):1955‐61. Source: Symphony Health Solutions PHAST Data Set

Obesity Pharmacology: Prescribers and Prescription Volume

% New Anti‐obesity Pharma by RegionU.S., 2012‐2015

Prescriptions Dispensed, U.S., 2012‐2015

74% Phentermine

18.6% new anti‐obesity pharma

MARKETSHARE

0

2500

5000

7500

10000

2013 2014 2015

Phentermine Qsymia Belviq Contrave Saxenda

TRx’s (000

)

7,5278,213

9,189

10.90% Compound Annual Growth Rate2

8

Case :

• A 52‐year‐old woman with obesity (BMI 38) presents with multiple comorbidities– Has a 7‐year history of T2DM and has gained a significant amount of weight

since being placed on insulin 6 months ago – Has remarkable medical history for atrial fibrillation, hypertension,

proteinuria, and sleep apnea

She was unable to lose weight after 6 months of improving her diet and increasing physical activity

T2DM: type 2 diabetes mellitus.

Interactions Among Hormonal and Neural Pathways1

AGRP: agouti‐related peptide; α‐MSH: α‐melanocyte‐stimulating hormone; GHSR: growth hormone secretagoguereceptor; INSR: insulin receptor; LepR: leptin receptor; MC4R: melanocortin‐4 receptor; NPY: neuropeptide Y; POMC: proopiomelanocortin; PYY: peptide YY; Y1R; neuropeptide Y1 receptor; Y2R: neuropeptide Y2 receptor.1. Apovian CM Aronne LJ Bessesen D et al. J Clin Endocrinol Metab. 2015;100:342‐362.

J Clin Invest. 2012 Jan 3;122(1):153‐62. doi: 10.1172/JCI59660. Epub 2011

Why Don’t People Just Lose Weight!

14% Weight Loss Produced Changes in 8 Hormones That Encourage Weight Regain

Might Need More Than One Drug

14% Weight Loss:Reduced IncreasedLeptin ‐ 65%Peptide YYCholecystokininInsulinAmylin

GhrelinPancreatic polypeptideGastric inhibitory polypeptide

Measures of appetite

10-week, lifestyle-based weight loss intervention in healthy overweight and obese adults (n=34) led to sustained elevations in appetite stimulating hormone(s) and decreases in appetite suppressing hormones

Sumithran P et al. N Engl J Med. 2011;365:1597-1604. 12NET RESULT OF THESE HORMONAL CHANGES is WEIGHT GAIN!

That’s why patients hit a weight loss plateau. Can you overcome it?

The same way you overcome hyperglycemia, or hypertension in someone who doesn’t respond

to a single agent.

Add more medication Key point : diet and behavior are like a medication – Low carb diets increase TEE

If that doesn’t work: Consider a procedure.

Key Point: Don’t give up

Shukla AP, Iliescu RG, Thomas CE, Aronne LJ. Food Order has a Significant Impact on Post–prandial Glucose Levels. Late Breaking Abstract. The Obesity Society’s 2014 Annual Scientific Meeting, Obesity Week. Boston, MA.

Bread firstVegs and chicken 15 min later

Vegs and chicken firstBread 15 min later

Good Advice:Protein and Vegs firstAUC glucose ‐73%

Antiobesity Agents and Their Mechanism of Action1

1. Apovian CM Aronne LJ Bessesen D et al. J Clin Endocrinol Metab. 2015;100:342‐362.

PHEN/TPM ER 7.5/46 Produces Greater Weight Loss thanPHEN 15 or TPM ER 92:

Combination Better Than 2x the Dose of Monotherapy

PHEN: phentermine; TPM: topiramate.1. Aronne LJ et al. Obesity. 2013;21:2163‐2171.

Weight Loss With Lorcaserin/Phentermine: Combination Produces Greater Weight Loss

N = 238

LOR: lorcaserin; IR: immediate release; QD: daily.1. Smith S et al. ObesityWeek 2014. Abstract 2053P.

a LOR/PHEN IR QD = LOR 10 mg BID + PHEN IR 15 mg QD; LOR/PHEN IR BID = LOR 10 mg BID + PHEN IR 15 mg BID; LOR + PHEN is not FDA approved for the treatment of obesity/overweight in the United States.

N = 238

3‐Month Safety Study

PHARMACOLOGICAL MANAGEMENT of

OBESITY: An Endocrine Society Clinical

Practice Guideline

January 15, 2015

. Apovian CM Aronne LJ Bessesen D et al. J Clin Endocrinol Metab. 2015;100:342‐

Pharmacotherapy for Obesity

a Mean weight loss in excess of placebo as percentage of initial body weight or mean kg weight loss over placebo.GABA: gamma‐aminobutyric acid; GLP‐1: glucagon‐like peptide‐1.

1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.

Drug Mechanism of Action Mean Weight Lossa Study Duration

Phentermine Norepinephrine‐releasing agent 3.6 kg 2 to 24 weeks

Diethylpropion Norepinephrine‐releasing agents 3.0 kg 6 to 52 weeks

Orlistat Pancreatic and gastric lipase inhibitor 2.9 to 3.4 kg(2.9 to 3.4%) 1 year

Lorcaserin 5HT2C receptor agonist 3.6 kg (3.6%) 1 year

Phentermine/topiramate

GABA receptor modulation (topiramate) plus norepinephrine‐releasing agent (phentermine)

6.6 kg (6.6%) (recommended dose)

8.6 kg (8.6%)(high dose)

1 year

Naltrexone bupropion

Reuptake inhibitor of dopamine and norepinephrine (bupropion) and opioid antagonist (naltrexone)

4.8% 1 year

Liraglutide GLP‐1 agonist 5.8 kg 1 year

19

Pharmacotherapy for Obesity:

a Mean weight loss in excess of placebo as percentage of initial body weight or mean kg weight loss over placebo.GABA: gamma‐aminobutyric acid; GLP‐1: glucagon‐like peptide‐1.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.

Drug Mechanism of Action Mean Weight Lossa Study Duration

Phentermine resin Norepinephrine‐releasing agent 3.6 kg 2 to 24 weeks

Diethylpropion Norepinephrine‐releasing agents 3.0 kg 6 to 52 weeks

Orlistat Pancreatic and gastric lipase inhibitor

2.9 to 3.4 kg, 2.9% to 3.4% 1 year

Lorcaserin 5HT2C receptor agonist 3.6 kg, 3.6% 1 year

Phentermine/topiramate

GABA receptor modulation (topiramate) plus

norepinephrine‐releasing agent (phentermine)

6.6 kg (recommended

dose), 6.6%; 8.6 kg (high dose), 8.6%

1 year

Naltrexone bupropion

Reuptake inhibitor of dopamine and norepinephrine (bupropion)

and opioid antagonist (naltrexone)

4.8% 1 year

Liraglutide GLP‐1 agonist 5.8 kg 1 year

Common side effects of obesity treatmentsKey Point: Side Effects Guide Treatment

Drug Common Side EffectsPhentermine resin Headache, elevated BP, elevated heart rate, insomnia, dry

mouth, constipation, anxiety; palpitation, tachycardia, Diethylpropion

Orlistat Decreased absorption of fat‐soluble vitamins, steatorrhea, oily spotting, fecal urgency, oily evacuation, increased defecation

Lorcaserin Headache, nausea, dry mouth, dizziness, fatigue, constipationPhentermine/topiramate

Insomnia, dry mouth, constipation, paresthesia, dizziness, dysgeusia

Naltrexone bupropion Nausea, constipation, headache, vomiting, dizziness

Liraglutide Nausea, vomiting


Advantages and Disadvantages Associated With Weight‐Loss Medications1At present, prescribing is often based on cost and side effect profile

a Less weight loss = 2%‐3%; greater weight loss = >3%‐5%; robust weight loss = >5%. b Long‐term data is 1‐2 years.


Drug Advantages Disadvantages

Phentermine Inexpensive, greater weight lossa

Side‐effect profile, no long‐term datab

Topiramate/phentermine Robust weight lossa, long‐term data Expensive, teratogen

Lorcaserin Side‐effect profile, long‐term datab Expensive

Orlistat, prescription Nonsystemic, long‐term datab

Less weight lossa, side‐effect profile

Orlistat, over the counter Inexpensive Less weight lossa, side‐effect profile

Natrexone/bupropion Greater weight lossa, food addiction, long‐term datab

Side‐effect profile,mid‐level price range

Liraglutide Side‐effect profile, long‐term datab Expensive, injectable

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Lorcaserin1

MAOI: monoamine oxidase inhibitor; SNRI: serotonin–norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.

Action Mean Weight Lossa

Study Duration

Common Side Effects Contraindications

5HT2creceptor agonist

3.6 kg, 3.6% 1 year

Headache, nausea, dry mouth,

dizziness, fatigue, constipation

• Pregnancy and breastfeeding

• Use with caution:– SSRI, SNRI/MAOI– St. John’s wort– Triptans– Buproprion– Dextromethorphan

a Mean weight loss in excess of placebo as percentage of initial body weight or mean kg weight loss over placebo.

Weight Loss With Lorcaserin: BLOOM Trial1a

• Study patients: BMI 30‐45 or BMI 27‐30 with risk factors (hypertension, CVD, dyslipidemia, impaired glucose tolerance, or obstructive sleep apnea)

• At 1 year, 55.4% of patients receiving lorcaserin and 45.1% of patients receiving placebo remained in the trial

• Weight loss with lorcaserin (10 mg twice daily) vs placebo, 52 weeks

• Small but significant decreases in blood pressure in lorcaserin vs placebo groups

• Rates of headache and nausea greater in treatment vs placebo groups

ITT: intention‐to‐treat; LOCF: last observation carried forward.1. Smith SR et al. N Engl J Med. 2010;363:245‐256.

a Based on ITT‐LOCF analysis.

Weight Loss Lorcaserin(n = 1,538)

Placebo(n = 1,499) P

≥5% 47.5% 20.3% <.001

≥10% 22.6% 7.7% <.001

Mean weight loss 5.8 kg 2.2 kg <.001

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Weight Loss With Lorcaserin: BLOOM Trial1a

• Study patients: BMI 30‐45 or BMI 27‐30 with risk factors (hypertension, CVD, dyslipidemia, impaired glucose tolerance, or obstructive sleep apnea)

• At 1 year, 55.4% of patients receiving lorcaserin and 45.1% of patients receiving placebo remained in the trial

• Weight loss with lorcaserin (10 mg twice daily) vs placebo, 52 weeks

• Small but significant decreases in blood pressure in lorcaserin vs placebo groups

• Rates of headache and nausea greater in treatment vs placebo groups

ITT: intention‐to‐treat; LOCF: last observation carried forward.1. Smith SR et al. N Engl J Med. 2010;363:245‐256.


Weight Loss Lorcaserin(n = 1,538)

Placebo(n = 1,499) P

≥5% 47.5% 20.3% <.001

≥10% 22.6% 7.7% <.001

Mean weight loss 5.8 kg 2.2 kg <.001

The Power of Obesity Treatment: Improvement in Multiple Risk

Factors:Lorcaserin

Lorcaserin FDA EMDAC26

Lorcaserin: Cardiometabolic Effects1

HDL: high‐density lipoprotein; LDL: low‐density lipoprotein; mITT: modified intention to treat.1. Aronne L et al. Postgrad Med. 2014;126:7‐18.

*P ≤ .001; ** P < .05; *** P < .001.

Lorcaserin: Those Who Lost ≥4.5% Total Body Weight by Week 12 Were Week 52 Responders1

Studies 009 and 011, mITT

mITT Lorcaserin BID Week 12 Completed Week 12 Completed Week 52

N = 3097 ≥4.5% weight loss 1369/3097 (44.2%) 1083/1369 (79.1%)

<4.5% weight loss 1168/3097 (37.7%) 680/1168 (58.2%)

BID: twice daily.1. Slide courtesy Dr. Steve Smith; May 10, 2012 FDA Advisory Committee Meeting.

Chan

ge, %

Key Point: if it doesn’t work, stop

Phentermine/Topiramate ER1

Action Mean Weight Lossa

Study Duration


GABA receptormodulation

(topiramate) plus norepinephrine‐releasing agent (phentermine)

6.6 kg (recommended dose), 6.6%; 8.6 kg (high dose), 8.6%

1 year

Insomnia, dry mouth,

constipation,paresthesia, dizziness, dysgeusia

Pregnancy andbreastfeeding,

hyperthyroidism,glaucoma, MAOI,sympathomimetic

amines

ER: extended release.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.


Weight Loss With Phentermine/Topiramate ER CONQUER Trial1a

Weight LossTopiramate/Phentermine

7.5 mg/46 mg Daily(n = 1,538)

Topiramate/Phentermine

15 mg/92 mg Daily(n = 981)

Placebo(n = 979) P

≥5% 62% 70% 21% <.001

≥10% 37% 48% 7% <.001

Mean weight loss 8.1 kg 10.2 kg 1.4 kg <.001

• Patients: BMI 27‐45 and ≥2 obesity‐related comorbidities (hypertension, dyslipidemia, type 2 diabetes, prediabetes, abdominal obesity)

• Weight loss, 56 weeks

• Dose‐related AEs: dry mouth, constipation, dysgeusia, paresthesia, insomnia, dizziness, anxiety, irritability, disturbance in attention

• Endpoint assessments were not available for 31% of participants

1. Gadde KM et al. Lancet. 2011;377:1341‐1352.

a Based on ITT‐LOCF analysis.30

Weight Loss With Phentermine/Topiramate ER: CONQUER Trial1a

Weight Loss

Topiramate/Phentermine7.5 mg/46 mg Daily

(n = 1,538)

Topiramate/Phentermine15 mg/92 mg Daily

(n = 981)

Placebo(n = 979) P

≥5% 62% 70% 21% <.001

≥10% 37% 48% 7% <.001

Mean weight loss 8.1 kg 10.2 kg 1.4 kg <.001

• Dose‐related AEs: dry mouth, constipation, dysgeusia, paresthesia, insomnia, dizziness, anxiety, irritability, disturbance in attention

• Endpoint assessments were not available for 31% of participants

• Patients: BMI 27‐45 and ≥2 obesity‐related comorbidities (hypertension, dyslipidemia, type 2 diabetes, prediabetes, abdominal obesity)

• Weight loss, 56 weeks

1. Gadde KM et al. Lancet. 2011;377:1341‐1352.


Phentermine/Topiramate ER: Cardiometabolic Effects1,2

• Significant dose‐related reductions in systolic and diastolic pressure in patients with hypertension

• Significant reductions in fasting glucose, HbA1c, and insulin in patients with prediabetes

• Significant improvements in lipid profiles in patients with hypertriglyceridemia

• Significant improvement in sleep apnea ‐ AHI2‐

AHI: apnea–hypopnea index .1. Gadde KM L et al. Lancet. 2011;377:1341‐1352. 2. Winslow DH et al. Sleep. 2012;35:1529‐1539.

Liraglutide1

ActionMean Weight Lossa

Study Duration


GLP‐1 agonist 5.8 kg 1 year Nausea,

vomiting,

PancreatitisMedullary thyroidcancer history,

multiple endocrineneoplasia type 2

history



Liraglutide: Weight Loss Over 2 Years1

1. Astrup A et al. Int J Obes (Lond). 2012;36:843‐854.

All patients on liraglutide/placebo switched to liraglutide 2.4 mg at week 52, and then to

3.0 mg between weeks 70 and 96

Patients: BMI 30‐40 Weight loss: 104 weeks

Weight Loss With Liraglutide: SCALE Studies

1. Greenway FL et al. The Obesity Society Annual Meeting at ObesityWeek 2014 (ObesityWeek 2014). Abstract 3027‐OR. 2. Kushner FL et al. ObesityWeek 2014. Abstract 3030‐OR.

• Study patients: nondiabetic subjects with obesity and overweight with comorbidities

• Randomized 2:1 to liraglutide 3.0 mg (n = 2487) or placebo (n = 1244) as an adjunct to diet and exercise

SCALE: Obesity and Prediabetes1 SCALE: Diabetes2

• Study patients (n = 864): overweight or obese subjects with type 2 diabetes

• Randomized to liraglutide 3.0 mg or placebo as an adjunct to diet and exercise

Impact of Liraglutide on Cardiometabolic Effects and HRQL: SCALE Studies

FPG: fasting plasma glucose ; SF: short form.1. O’Neil P et al. 97th Annual Meeting of the Endocrine Society (ENDO 2015). Abstract SAT‐572. 2. Kushner FL et al. ObesityWeek 2014. Abstract 3030‐OR. 3. Blackman A et al. 50th Annual Meeting of the European Association for the Study of Diabetes (EASD 2014). Abstract OR‐184.

• Health‐related quality of life improved significantly with liraglutide 3 mg but not with 1.8 mg

SCALE: Obesity and Prediabetes: Subgroup Analysis1

SCALE: Diabetes2

• Reductions in FPG were greater with liraglutide vs placebo (−8.3 vs −2.8 mg/dL, respectively)

• Reduction in systolic blood pressure were greater with liraglutide vs placebo in both responders (−5.5 vs −3.4 mmHg, respec vely)

• Changes in overall physical health scores (SF‐36) were greater for liraglutidecompared with placebo (+4.3 vs +4.1, respectively)

SCALE: Sleep Apnea3

• Liraglutide 3 mg compared with placebo produced significant improvements in AHI

Naltrexone/Bupropion1

ActionMean Weight Lossa

Study Duration


Reuptake inhibitor of

dopamine and norepinephrine (bupropion) and opioid antagonist (naltrexone)

4.8% 1 year

Nausea, constipation, headache,vomiting, dizziness

Uncontrolledhypertension,

seizuredisorders, anorexianervosa or bulimia,drug or alcohol

withdrawal, MAOI



Change in Body Weight With NB: COR‐II1

* P < .001 vs placebo at all time points.NB: naltrexone sustained‐release (SR) (32 mg/day) plus bupropion SR (360 mg/day). 1. Apovian CM et al. Obesity. 2013;21:935‐943.

Proportion of Participants Who Lost Weight With Naltrexone/Bupropion: COR‐II1

* P < .001 vs placebo at all time points.1. Apovian CM, et al. Obesity . 2013;21:935‐943.

39


a Less weight loss = 2%‐3%; greater weight loss = >3%‐5%; robust weight loss = >5%. b Long‐term data is 1‐2 years.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.












40













a Less weight loss = 2%‐3%; greater weight loss = >3%‐5%; robust weight loss = >5%. b Long‐term data is 1‐2 years.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.

74.585.1

65.8 6573

49.1

64.3

35.2 39 41

0.00

25.00

50.00

75.00

100.00

PHEN/TPM7.5/46

PHEN/TPM15/92

LOR 10 BID BUP/NAL32/360

LIR 3.0

Patie

nts, %

5% weight loss 10% weight loss

a Combined with lifestyle modification.

Odds of Reducing Body Weight by % Categories at 1 Year With Adjunctive Medication Among Those Who Complete Treatment

3

Slide 42

3 can you get rid of the references and make the picture biggerWeill Cornell Medical College, 2/2/2016

Questions you may have???

• Q: What medicine should I use for which patient?• A: Based on side effect profile and coverage

• Q: What about metformin?• A: It works

• Q: What do you use for drug‐induced weight gain?• A: Depends on the drug, how critical, what the MD prescribing it says

DPPOS – 10 year Follow‐Up Data

CONCLUSIONS: “Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for

at least 10 years of treatment”

Diabetes Prevention Program Research Group. Diabetes Care. 2012 Apr;35(4):731-7

Salpeter SR, et al. AJM 2008;121:149.

Metformin Reduces BMI

Metformin Reduces BMI in Non‐diabetics

Salpeter SR, et al. AJM 2008;121:149.

MAOI: monoamine oxidase inhibitor; SSRI: selective serotonin reuptake inhibitor.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.

Category Drug Class Weight Gain Alternatives

Psychiatric agents

AntipsychoticClozapine, risperidone,olanzapine, quetiapine,

haloperidol, perphenazineZiprasidone, aripiprazole

Antidepressants/mood stabilizers: tricyclic antidepressants

Amytriptyline, doxepin,imipramine, nortriptyline,trimipramine, mirtazapine

Bupropiona, nefazodone,fluoxetine (short term), sertraline (<1 year)

Antidepressants/mood stabilizers: SSRIs

Fluoxetine?, sertraline?,paroxetine, fluvoxamine

Antidepressants/mood stabilizers: MAOIs Phenylzine, tranylcypromine

Lithium —

Neurologic agents Anticonvulsants Carbamazepine, gabapentin,

valproateLamotrigine?,

topiramatea, zonisamidea

Endocrinologicagents Diabetes drugs

Insulin (weight gain differs with type and regimen used),

sulfonylureas, thiazolidinediones, sitagliptin?, metiglinide

Metformina, acarbosea, miglitola, pramlintidea, edenatidea, liraglutidea

a Weight‐reducing.

Drugs Associated With Weight Gain and Suggested Alternatives1

Category Drug Class Weight Gain Alternatives

Gynecologic agents

Oral contraceptives

Progestational steroids, hormonal contraceptivescontaining progestational

steroids

Barrier methods, IUDs

Endometriosis treatment Depot leuprolide acetate Surgical methods

Cardiologic agents Antihypertensives α‐blocker?, β‐blocker?

ACE inhibitors?, calcium channel blockers?,

angiotensin‐2 receptor antagonists

Infectious disease agents Antiretroviral therapy Protease inhibitors —

GeneralSteroid hormones Corticosteroids, progestational

steroids NSAIDs

Antihistamines/ anticholinergics

Diphenhydramine?, doxepin?, cyproheptadine?

Decongestants, steroid inhalers

IUD: intrauterine device.1. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342‐362.

Drugs Associated With Weight Gain and Suggested Alternatives (Cont’d)1

0% 5% 10% 15% 20% 25% 30% 35% Weight Loss

Treatment Gap in Mid‐BMI Range

Lap BandGastric Bypass

TreatmentGap

NOT EFFECTIVE

enoughfor many

people

Diet and Lifestyle& Drugs prior to 2012• Orlistat • Phentermine

TOO RISKY for many people

After Aronne L. FDA EMDAC 2010.

BPD

Sleeve gastrectomy

The gap is being filled

49

0% 5% 10% 15% 20% 25% 30% 35% Weight Loss

Treatment Gap in Mid‐BMI Range

Lap BandGastric Bypass

TreatmentGap

NOT EFFECTIVE

enoughfor many

people

Diet and Lifestyle& Drugs prior to 2012• Orlistat • Phentermine

TOO RISKY for many people

After Aronne L. FDA EMDAC 2010.

BPD

Sleeve gastrectomy

More Drug options:

LorcaserinLiraglutide

Combination Pharmacotherapy

Phen/topNalt/bup

Less Invasive Procedures

Vagal block therapyEndoscopic sleeve

More Drug options (2015):• Lorcaserin• Liraglutide

The gap is being filled

New drugs and devices can reduce weight and weight‐related comorbidities

50

Documents

Sanford I. Weill Professor of Metabolic Research Weill ...syllabus.aace.com/2016/chapters/lower-new-york/presentations/5...Gaps Between 2015 Obesity Pharmacology ... her diet and increasing