Welcome to CMHC WEST

Ken Fujioka, M.D.Director of Nutrition and Metabolic Research

Wireless Weight loss Dept. of Scripps Clinic Dept. of Diabetes and Endocrine

Sharp Liberty Station Obesity Symposium May 31, 2019

Recently Approved Weight Loss Medications

Medication Target

Lorcaserin Serotonin 5HT-2c agonist (non-stimulant)

Phentermine/topiramate Sympathomimetic / anti-seizure medication that enhances the inhibitory effect of GABA

Naltrexone/bupropion opioid receptor antagonist /catecholamine reuptake inhibitor

Liraglutide GLP-1 receptor agonist

Fujioka K. Current and emerging medications for overweight or obesity in people with comorbidities. Diabetes Obes Metab. 2015 Jun 4

HypothalamusNYP POMC

Eat (Hunger) Stop Eating

GastrointestinalTrack

Fat Cells Pancreas

Amylin, InsulinGLP-1, GLP-2, PYY, and many more

Leptin

Dorsal Vagal Complex

Hind BrainStop Eating

Hypothalamus

NYP POMC

Eat (Hunger) Stop Eating

Vagal Afferent fibersGastrointestinal

TrackFat

Cells Pancreas

Dorsal Vagal Complex

Hind BrainStop Eating

Hypothalamus

NYP POMC

Eat (Hunger) Stop Eating

Vagal Afferent fibersGastrointestinal

TrackFat

Cells Pancreas

5HT2csatiety

Lorcaserin

Lorcaserin 5HT2c agonist

DopamineNor-epinephrine

Opioid Motivated reward

eating

Dorsal Vagal Complex

Hind BrainStop Eating

Hypothalamus

NYP POMC

Mesolimbic systemReward centersNucleus accumbensPrefrontal cortex

Eat (Hunger) Stop Eating

Vagal Afferent fibersGastrointestinal

TrackFat

Cells Pancreas

Bupropion/NaltrexonePhentermine/Topiramate

DopamineNor-epinephrine

Motivated reward eating

Dorsal Vagal Complex

Hind BrainStop Eating

Hypothalamus

NPY POMC

Mesolimbic system

Stop Eating

Vagal Afferent fibersGLP-1 Gastrointestinal Track

Increase eating

Liraglutide GLP-1 Hormone

ITT Weight loss at one year without intensive behavior modification

0

2

4

6

8

10

12

Naltrexone/Bupropion Lorcaserin Liraglutide Phentermine/Topiramate

Percent Weight Loss

Percent Weight Loss

Fujioka K. Current and emerging medications for overweight or obesity in people with comorbidities. Diabetes Obesity Met. 2015 doi:10.1111/dom.12502 3

Effect of Phentermine/Topiramate ER on Weight Loss in Obese Adults Over 2 Years

9Garvey WT, et al. Am J Clin Nutr. 2012;95:297-308.

-9.3%

-10.5%

-1.8%

Data are shown with least squares mean (95% CI).

SEQUEL Study

Placebo

Phentermine/topiramate CR 7.5/46

Phentermine/topiramate CR 15/92

Phentermine/Topiramate ER: EQUIP and CONQUERMost Commonly Reported Treatment Emergent Adverse Events

10

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 infection 12.8 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 and topiramate extended-release [package insert]. Mountain View, CA: Vivus; 2012.

Phentermine/Topiramate

• Very potent weight loss agent• Positive studies in Binge Eating (topiramate)

• Significant number of potential Adverse Events (two drugs two sets of potential AEs)• REMS program: potential for teratogenicity, cleft lip

and cleft palate• Suicide, mood, and sleep disorders (topiramate)

• Acute myopia and glaucoma (topiramate)• Cognitive impairment (topiramate)

• Phentermine: sympathomimetic that can increase heart rate and blood pressure

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

Clinical Pearls and Phentermine/Topiramate ER

• Balance significant weight loss with potential for adverse events

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

• Despite the fact that this medication contains a sympathomimetic it did not typically increase blood pressure but does increase pulse

• Recommend the middle 7.5/46mgs dose • Weight loss at 2 years very similar to highest dose• If the patient needs to stop they do not have to

taper down

Buproprion – Naltrexone

Greenway, FL, Fujioka, K et al. Lancet. 2010;376(9741):595-605

0

-2

-4

-6

-8

-100 4 8 12 16 20 24 28 32 36 40 44 48 52 56

Weeks

Wei

ght c

hang

e fr

om b

asel

ine

(%)

Placebo

Naltrexone 16 mg plus bupropion

Naltrexone 32 mg plus bupropion

Change in Selected Items from the Control of Eating Questionnaire at Week 56

14

*P <.05 vs placebo.

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

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 -5Less Change from baseline (mm) More

*

**

**

*

*

*

Placebo (n=511)

Naltrexone 16 mg plus bupropion (n=471)

Naltrexone 32 mg plus bupropion (n=471)

Prevalence of Cravings

0.5230.568

0.648

0.545

0.273

0.398

0.261

0.543 0.554

0.739

0.467

0.315

0.446

0.25

0.475

0.594

0.762

0.416

0.218

0.376

0.178

0.512

0.573

0.719

0.473

0.267

0.406

0.228

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

A B C D E F G

Chart 3: Perceptions

1 (<50) 2 (50-65) 3 (>65) TotalCravings

MacMillan M, Cummins K, Fujioka K What weight loss treatment options do geriatric patients with overweight and obesity want to consider? Obes Sci Pract. 2016 Dec;2(4):477-482

Adverse Events

• Nausea • (Forced Titration in studies)

• Constipation• Headache• Vomiting• Dizziness• Insomnia

• Take second dose late afternoon not late evening

• Dry mouth

Naltrexone ER /Bupropion SR 32mg/360 mg

N=2545%

Clinical Pearls Bupropion/Naltrexone

• May have added benefit in the depressed obese patient • Be cautious with combining with other depression

meds (potential for interaction)• Has potential to work on “Cravings” and food reward

type eating• Recommend slow titration due to nausea • May not need to go to the highest dose, in clinical

practice many patients lose weight on lower doses

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

• Bulimics • One to two mmHg rise in blood pressure and pulse (check

BP the first 12 weeks) • Do not give to patient on chronic opioids• Do not give with high fat meal

Lorcaserin—BLOOM Study:Body Weight Over Years 1 and 2*

*Only included patients who continued the study past year 1.Smith SR et al. N Engl J Med. 2010;363(3):245–256.

BLOOM = Behavioral Modification and Lorcaserin for Overweight and Obesity Management.

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

20

0 4 8 12 16 20 24 28 32 36 40 44 48 52-15

-10

-5

0

Responder:Lorcaserin BID

Non-Responder:Lorcaserin BID

Week

%Change

Studies 009 and 011, MITT

-10.22%

MITT Lorcaserin BID Week 12 Completed Week 12 Completed Week 52N = 3097 ≥4.5% wt loss 1369/3097 (44.2%) 1083/1369 (79.1%)

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

STOP -2.46%

Responder: Lorcaserin BID

Non-responder: Lorcaserin BID

Slide courtesy Dr. Steve Smith; May 10, 2012 FDA Advisory Committee Meeting

Lorcaserin for Weight Loss in Type 2 DM

O’Neil PM, et al. Obesity (Silver Spring). 2012 Jul;20(7):1426-36.

New Studies in Obesity medicine:CardioVascular Outcome Trials (CVOT)

Enroll 10,000 or more patients with known cardiovascular disease or diabetes with multiple risk factors for impending cardiovascular disease

Randomize to placebo or study drug and followed for 3-5 years

This has to be completed for most weight loss medications as well as diabetic medications

Sibutramine 1997-2010

9

9.5

10

10.5

11

11.5

12

Placebo Sibutramine

% of major adverse cardiovascular events

% of major adverse cardiovascular events

Sibutramine: norepinephrine, serotonin, and

dopamine reuptake inhibition

Approved as a weight loss medication in 1997

Published their CardioVascularOutcomes Trial in 2010

Subjects with preexisting cardiovascular conditions receiving sibutramine had an increased risk of nonfatal myocardial infarction and nonfatal stroke

Removed from the market in 2010

Status of Cardiovascular Outcome Trials (CVOT) Weight loss medication Status of CVOT

Lorcaserin Completed (2018)

Phentermine/Topiramate Not completed

Naltrexone/Bupropion 2015 CVOT trial stopped prematurely*

Liraglutide 3.0 mg FDA allowed use of Liraglutide 1.8 mg dataLiraglutide felt to be CVOT safe and a CVOT not required

“Orexigen shared the CVOT data with over 100 individuals both within and outside the company (data leaked)When the FDA found out the company was told to continue the trial but must do a second CVOT trial. The CVOT interim data was released by the company to the public in a patent application and the executive committee of the study felt the study was unblinded And it was completely terminated. Medpage Today in collaboration with AACE April 13,2016

Cardiovascular Safety of Lorcaserin in Obesity

Randomize 12,000 patients with Cardiovascular disease (75%) and/or Diabetes (57%) with multiple cardiovascular risk factors

Randomized half the patients to lorcaserin and half to placebo

Primary outcome: cardiovascular event • (example stroke, myocardial infarction, heart failure, angina etc.)

NEJM E.A. Bohula, S.D. Wiviott, D.K. McGuire et. Al. August 2018

Cardiovascular Safety of Lorcaserin in Obesity

12.5

12.6

12.7

12.8

12.9

13

13.1

13.2

13.3

13.4

Placebo Lorcaserin

Percent of patients having a cardiovascular event

Percent of patients having a cardiovascular event

At the end of 36 months 12.8% of patients in the Lorcaserin group had a Cardiovascular event13.3% of patients in the Placebo group had a Cardiovascular event

Lorcaserin group lost more weight (4.2 kg vs 1.4 kg) at one year

This was a safety trial not a weight loss study

Adverse events: 13 Lorcaserin patients vs 4 placebo patients had serious hypoglycemia

NEJM E.A. Bohula, S.D. Wiviott, D.K. McGuire et. Al. August 2018

Clinical Practice Pearls

• Low side effect profile with no stimulating effects• Safe in the High Risk Cardiovascular patient #

• Can be used in patients on SSRIs• Hypoglycemia a risk in diabetic patients on a

sulphonylureas or insulin

• # Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guidelines

Caroline M. Apovian, Louis J. Aronne, Daniel H. Bessesen, J Clin Endocrinol Metab 100: 342–362, 2015

DopamineNor-epinephrine

Motivated reward eating

Dorsal Vagal Complex

Hind BrainStop Eating

Hypothalamus

NPY POMC

Mesolimbic system

Stop Eating

Vagal Afferent fibersGLP-1 Gastrointestinal Track

Increase eating

Effects size of meal ( smaller portions) = SatietyLonger time between meals (less hunger) = decreased Hunger

Liraglutide GLP-1 hormone

Effects of Liraglutide and Orlistat on Body Weight in Nondiabetic Obese Adults

Astrup A, et al. Lancet.2009;374:1606-1616.Data are mean (95% CI) for the ITT population

Liraglutide 3.0 mgs given to patients after a 6% weight loss

Liraglutide

Liraglutide

Liraglutide Package insert NovoNordisk 2015 (Wadden et al.)

Rate of death from any cause lower in liraglutide group (381 patients [8.2%] vs placebo group (447 [9.6%])

Liraglutide 1.8 mgs: Lower Rate of Death1

1. Gudzune KA et al. Ann Intern Med. 2015;162:501-512.

Adverse Events in Pivotal trial

• Nausea - 40.2%• Titrate slowly

• Vomiting - 16.3%• Pancreatitis - 0.2%

• Placebo - 0.0• Diarrhea – 20.9%• Constipation – 20.0%• Decreased appetite - 10.8%• Hypoglycemia in Diabetic Study

• Increased in patients on sulphonylureas

Clinical Pearls Liraglutide

•Useful in the obese pre-diabetic and diabetic patient

•Non-stimulating (non-sympathomimetic) and useful in the cardiovascular patient•Improvement in blood pressure •Improvement in lipids

•Titrate slowly as GI side effects are common•Has data showing weight loss in the patient that has already lost weight on their own

Bottom Line

For the high risk cardiovascular patient• Lorcaserin = safe• Liraglutide = safe (superiority)

At this time no completed CVOT studies • Naltrexone/Bupropion not recommended• Phentermine/topiramate not recommended

Non-systemic superabsorbent hydrogels: Technically a device but in a pill

The only superabsorbent hydrogel made from naturally-derived building blocks

3D cross-linked matrix

Carboxymethylcellulose (CMC)

CMC is cellulose that has been oxidized

Citric acid is naturally found in citrus fruits

Citric AcidBuilding blocks are Generally

Regarded As Safe (GRAS) by FDA

35

Super Absorbent Hydrogel Approved April 2019

• Oral Capsule administered with 500 cc of water before lunch and dinner

• Particles released and expand (> 100X) in stomach by absorbing water

• Particles mix with food and designed to enhance satiety by increasing the volume and elasticity of stomach contents

• Particles maintain their 3D structure and are cleared with the liquefied food to the small intestine

• Particles degrade in the large intestine, water is released and reabsorbed, and remnants are eliminated

GLOW pivotal study 2 co-primary endpoints:A – Placebo adjusted weight lossB- 5% Responders

37

Greenway FL, Arrone LJ, Raben A, Et. Al. A Randomized, Double‐Blind, Placebo‐Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss, Obesity 2019;27:205-216

58%

(A) Percent change in body weight from baseline (day 0) to day 171 (after 2 days of washout) by treatment group. Error bars represent standard error of the mean (SEM).

(B) Percent responders with ≥ 5% (P = 0.0008), ≥ 7.5% (P = 0.0017), or ≥ 10% (P = 0.0107) weight loss in all patients.

(C) Percent change in excess body weight from baseline (day 0) to day 171 (after 2 days of washout) by treatment group. Error bars represent SEM.

(D) Adjusted odds ratio (95% confidence interval) for achieving ≥ 5% (2.0 [1.3‐3.0]), ≥ 7.5% (2.1 [1.3‐3.3]), and ≥ 10% (2.1 [1.2‐3.8]) weight loss.

*P < 0.05; **P < 0.001. All P values are from logistic regression models adjusted for baseline weight and stratification factors. GLOW, Gelesis Loss Of Weight study; ITT, intention‐to‐treat.

Reaching 3% weight loss at 8 weeks predicts responders (sensitivity and specificity > 80%)

38

Patients treated wholost ≥3% at 8 weeks

Patients treated who lost <3% at 8 weeks

-12

-10

-8

-6

-4

-2

0

0 30 60 90 120 150

Wei

ght C

hang

e fr

om B

asel

ine,

%

Study Day

n=77-2.1%

n=93-9.9%

Patients, n (%)Difference

(95% CI) P-valueGelesis100

(n = 223)

Placebo

(n = 211)Any AE probably or possibly related

88 (39.5) 64 (30.3) 9.1 (–0.2, 18.2) 0.0557

Eye disorders 0 (0) 1 (0.5) –0.5 (–3.0, 1.7) 0.4862GI Disorders 84 (37.7) 58 (27.5) 10.2 (1.0, 19.1) 0.0248General disorders 1 (0.4) 1 (0.5) –0.0 (–2.6, 2.4) 1.0000Infections and infestations 2 (0.9) 1 (0.5) 0.4 (–2.2, 3.1) 1.0000Investigations 3 (1.3) 3 (1.4) –0.1 (–3.3, 3.0) 1.0000Metabolism and nutrition disorders

0 (0) 4 (1.9) –1.9 (–5.1, 0.6) 0.0551

MSK and connective tissue disorders

2 (0.9) 0 (0) 0.9 (–1.5, 3.5) 0.4992

Nervous system disorders 4 (1.8) 2 (0.9) 0.8 (–2.2, 4.0) 0.6860Renal and urinary disorders 1 (0.4) 0 (0) 0.4 (–1.8, 2.9) 1.0000Reproductive disorders 0 (0) 1 (0.5) –0.5 (–3.0, 1.7) 0.4862Respiratory, thoracic disorders 1 (0.4) 1 (0.5) –0.0 (–2.6, 2.4) 1.0000Skin and subcutaneous disorders

1 (0.4) 3 (1.4) –1.0 (–4.0, 1.7) 0.3599

Adverse events coded as possibly or probably related by major category – most common category is GI

39

Patient with DM2

struggling with eating

large portions of food feeling out of control

• 42 year old female newly diagnosed type 2 diabetes • Sent by her primary care provider • The patient states she has always been healthy and

is very upset by the diagnosis of “diabetes” and asked to see a specialist

• Her only problem in life has been her weight. As early as a teenager she started gaining weight and has struggled her entire adulthood

• She is a very successful vice president of a biomedical research start up and has a MD/PhD in neurology

• She is very well dressed, engaging, and obviously highly intelligent

History

• She typically starts work at 8 AM and finishes around 8 PM. She realizes the need to be honest, and tells you about her struggles with food when she gets home from work.

• She will buy a “small pizza” on the way home from work. The pizza is 4 large slices and she has the intention of eating one or two slices.

• When she gets home she ends up eating the whole pizza and feels like she just can’t stop herself. She feels “very guilty” after she finishes as “I know better”. She only does this alone, and at times eats until she is uncomfortably full.

• This struggle with food will happen 3 to 4 times a week

Definition of Binge eating • Eating a large amount of food (Ex. two times a normal

portion) in a discrete period of time • Feeling out of control when eating

• Eating alone usually due to embarrassment • Eating rapidly• Eating until uncomfortably full• Continuing to eat even if not hungry • Feeling guilty, depressed or unhappy after binge eating • No compensatory behavior (Ex. vomiting, abuse of laxative, etc.)

Binge eating in the DM2 population• Prevalence varies from approximately 10 % to 25 % in women with DM2

• (compared to 2% in the general population)• Patients presenting to a weight loss clinic have a higher prevalence of 28%

• 47% of these pts will have impaired glucose tolerance (DM2 or Pre-DM2) • In the “Look Ahead trial” that studied weight loss in obese DM2 patients,

Baseline Binge eating in the last 6 months prior to starting the study 11.2% • DSM 5 criteria 1.1%

• Swedish study that followed Binge Eating disorders patients over 17 years found that one third became type 2 diabetics that required DM medications

• AM Chao, TA Wadden, AA Gorin, et. Al. Binge Eating and Weight Loss Outcomes in Individuals with Type 2 Diabetes: 4-Year Results from the Look AHEAD Study, Obesity (Silver Spring). 2017 November ; 25(11): 1830–1837

• Disordered Eating Behaviours in Women with Type 2 Diabetes MJ Kenardy, M Mensch, K Bowen et. Al. Eating behaviors 2001,2(2),183-192• L Clarine, K Kittleson, K Fujioka Incidence of Prediabetes in Patients with Binge Eating Disorder Seeking Weight Management Poster ADA 2017• Raevuori A, Suokas J, Haukka J et. Al. Highly increased risk of type 2 diabetes in patients with binge eating disorder and bulimia nervosa. Int J Eat

Disord. 2015 Sep;48(6):555-62. doi: 10.1002/eat.22334. Epub 2014 Jul 25.•

Binge eating disorder and Diabetes type 2

• Binge eating disorder is very common in the patient with DM2• Patients with Binge eating disorders and diabetes will be have

higher BMI compared to other diabetics• Binge patients may present with diabetes at a younger age

• (Scripps Clinic in house data)

• Binge appears to be an independent risk factor for DM2 • Binge eating disorder has an ICD 10 code

• S Abbott, N Dindol, AA Tahrani MK Piya. Binge eating disorder and night eating syndrome in adults with type 2 diabetes: a systematic review Journal of Eating Disorders (2018) 6:36 https://doi.org/10.1186/s40337-018-0223-1

• L Clarine, K Kittleson, K Fujioka Incidence of Prediabetes in Patients with Binge Eating Disorder Seeking Weight Management Poster ADA 2017

NeuroBiology of Binge Eating in Humans

• Genetic Form: MC4 receptor defect • Binge eating is a major phenotype of gene mutations of the

hypothalamic Melanocortin 4 Receptor • This receptor controls satiety or fullness after a meal • Heterozygous patients will present with severe obesity, hyperphagia, and

severe insulin resistance

• 5.1% of patients with severe obesity have a mutation of the MC4R receptor

• Treatment options: medications that can work post MC4R or downstream from MC4R Ex: GLP-1 working thru the hindbrain

• Branson R, Potoczna N, Kral J, et. Al. Binge Eating as a Major Phenotype of Melanocortin 4 Receptor Gene Mutations NEJM 2003; 348:1096-103

NeuroBiology of Binge Eating in Humans• Reward Circuitry involved in Binge eating

• Mesolimbic and Mesocortical Pathways (Reward Pathways) • Mesolimbic dopamine release seen in reward eating

• Lower dopamine activity in obese patients leads to overeating • Nucleus Accumbens – GABAergic and Glutamatergic activation produces

eating behavior • Potential areas to Treat Binge eating disorder

• Medications that can increase dopamine• Bupropion and Stimulants

• Medications that work thru the GABA system• Topiramate and Zonisamide = decreased food intake

• DJ Lee, GJB Elias, AM Lanzano. Neuromodulation for the treatment of eating disorders and obesity. Ther Adv Psychopharmacol 2018, Vol. 8(2) 73–92

Back to our patient: Physical exam and lab values:

• BMI of 41 Blood pressure 148/78 pulse 82 • A1c of 7.2 on Metformin 1,500 mgs per day • Urine mildly positive for microalbumin • Feet neurovascularly intact

• Type 2 diabetes with proteinuria • Borderline Blood pressure • Binge Eating Disorder (BED)

Treatment options in Binge Eating Disorder

• Approved Binge Eating Disorder treatments• Lisdexamfetamine dimesylate (L-lysine conjugated to

dextroamphetamine)• Not approved for weight loss or obesity treatment• Can Increase in blood pressure and pulse

• Increase associated with longer length of treatment • Common side effect leading to discontinuation (9%)

• Insomnia, Anxiety, Irritability, increased blood pressure, etc.

• Lisdexamfetamine should be avoided in patients with Heart disease

• NT Bello, BL. Yeomans. Safety of pharmacotherapy options for bulimia nervosa and binge eating disorder Expert Opin Drug Saf. 2018 January ; 17(1): 17–23. doi:10.1080/14740338.2018.1395854.

• K Ward, L Citrome Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2018 VOL. 14, NO. 2, 229–238

Other Treatment options (off Label) for binge

• GLP-1: Approved for Treatment for Diabetes and weight loss• Topiramate: Approved for Anti-seizure medication and

migraines • Zonisamide: Approved for Anti-seizure medication • Naltrexone/Bupropion: Approved for Weight loss

• SL McElroy, N Mori, AI Guerdjikova, PE Keck Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature Medical HypothesesVolume111, February 2018, Pages 90-93

• D. MARAZZITI, M. CORSI, S. BARONI European Review for Medical and Pharmacological Sciences Latest advancements in the pharmacological treatment of binge eating disorder 2012; 16: 2102-2107

• A. Halseth , K. Shan , K. Gilder et. Al. Quality of life, binge eating and sexual function in participants treated for obesity with sustained release naltrexone/bupropion Obesity Science & Practice 2018 Feb 23;4(2):141-152. doi: 10.1002/osp4.156. eCollection 2018 Apr

GLP-1 treatment in Binge Eating Disorder

• 42 patient randomized to Liraglutide (1.8 mgs) or placebo for 12 week

• Non Diabetics with Binge Eating Disorder• Noted a decrease in Binge Eating

• (Binge Eating Scale 20 decreased to 11) (placebo 22 to 18)• 81% went from Binge category to non-Binge status

• Weight loss of 4.5 kilos• Decrease in blood pressure • S. Robert. Improvement in binge eating in non-diabetic obese individuals after 3 months of treatment with

liraglutide — A pilot study Obesity Research & Clinical Practice (2015) 9, 301—304

Topiramate and BED: Mean Binges/Week

3.42

6.29

0.31

5.3

01234567

0 1 2 4 6 8 10 14

PlaceboTopiramate

MeanBinges/wk

P=.0004.McElroy SL et al. Am J Psychiatry. 2003;160:255-261.

Weeks

Topiramate and BED: Mean Weight Change–ITT

-1.16

-5.82

-7-6-5-4-3-2-10

0 1 2 4 6 8 10 14

PlaceboTopiramate

P=.005.McElroy SL et al. Am J Psychiatry. 2003;160:255-261.

Weeks

MeanWeightChange

(kg)

(2.6 lb)

(12.8 lb)

Topiramate and BED: Disposition of Subjects

• 51% of the patient on topiramate completed the trial • vs 61% on placebo

• 20% of the patients on topiramate had an adverse event leading to discontinuation

• Vs 9.7% on placebo

• McElroy SL et al. Am J Psychiatry. 2003;160:255-261

Zonisamide and Binge Eating 16 week trial

• Decrease in Binges per week • 4.5 binges to less than 0.5 binges

• Weight loss of 9 kilos in the Zonisamide group (1 kg in the placebo)• Over half the patient in the study withdrew before completion• Of the 30 patients on Zonisamide that started the study

• 8 (27%) discontinued due to adverse effects related to the medication• Psychological, cognitive, fall with fracture

• SL McElroy, R Kotwal, AI Guerdjikova et. Al. Zonisamide in the Treatment of Binge Eating Disorder With Obesity: A Randomized Controlled Trial J Clin Psychiatry 2006;67:1897–1906

Naltrexone 32 mgs SR /Bupropion 360 mgs SR and binge Eating

• Naltrexone/bupropion with Comprehensive lifestyle management vs Usual care for 26 weeks (82 patients in each group completed study)

• Binge Eating Scale • In patients with severe or moderate

Binge severity • 91% improved in the

Naltrexone/bupropion group• 18% improved in the Usual care

020406080

100

% improvement in BES categorization

% improvement in BES categorization

A Halseth , K Shan, K Gilder et. Al. Quality of life, binge eating and sexual function in participants treated for obesity with sustained release naltrexone/bupropion Obesity Science & Practice 2018 Feb 23;4(2):141-152.

Thanks for Attending and Listening !