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 Symposium May 31, 2019 Recently Approved Weight Loss Medications

Medication Target Serotonin 5HT-2c agonist (non- ) / Sympathomimetic / anti-seizure medication that enhances the inhibitory effect of GABA / 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 Eat () Stop Eating

Hypothalamus NYP POMC

Fat Gastrointestinal Cells Track Pancreas

Leptin GLP-1, GLP-2, PYY, and Amylin, Insulin many more Eat (Hunger) Stop Eating

Hypothalamus Dorsal Vagal Complex NYP POMC Hind Brain Stop Eating

Fat Gastrointestinal Pancreas Vagal Afferent fibers Cells Track Lorcaserin 5HT2c agonist

Eat (Hunger) Stop Eating

Lorcaserin Hypothalamus 5HT2c Dorsal Vagal satiety Complex NYP Hind Brain POMC Stop Eating

Fat Gastrointestinal Pancreas Vagal Afferent fibers Cells Track Bupropion/Naltrexone Dopamine Phentermine/Topiramate Nor-epinephrine Opioid Motivated reward eating Eat (Hunger) Stop Eating Mesolimbic system Reward centers Nucleus accumbens Hypothalamus Prefrontal cortex Dorsal Vagal NYP POMC Complex Hind Brain Stop Eating

Fat Gastrointestinal Pancreas Vagal Afferent fibers Cells Track Liraglutide GLP-1 Hormone

Dopamine Nor-epinephrine Motivated reward eating Increase eating Stop Eating

Mesolimbic system Hypothalamus

Dorsal Vagal NPY POMC Complex Hind Brain Stop Eating

GLP-1 Gastrointestinal Track Vagal Afferent fibers ITT Weight loss at one year without intensive behavior modification

Percent Weight Loss 12

10

8

6

4

2

0 Naltrexone/Bupropion Lorcaserin Liraglutide Phentermine/Topiramate 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 SEQUEL Study

Placebo -1.8%

Phentermine/topiramate CR 7.5/46-9.3%

-10.5% Phentermine/topiramate CR 15/92

Data are shown with least squares mean (95% CI). Garvey WT, et al. Am J Clin Nutr. 2012;95:297-308. 9 Phentermine/Topiramate ER: EQUIP and CONQUER Most Commonly Reported Treatment Emergent Adverse Events

Adverse Event (%) PHEN/TPM ER PHEN/TPM ER PHEN/TPM ER Placebo (N=3749) 3.75/23 7.5/46 15/92 Paresthesia 1.9 4.2 13.7 19.9 Dry mouth 2.8 6.7 13.5 19.1 6.1 7.9 15.1 16.1 Upper respiratory 12.8 15.8 12.2 13.5 tract infection 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 4.9 5.0 6.4 5.6

Phentermine and topiramate extended-release [package insert]. Mountain View, CA: Vivus; 2012. 10 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

Placebo 0 Naltrexone 16 mg plus bupropion Naltrexone 32 mg plus bupropion

-2

-4

-6

-8 Weight change from change baselineWeight (%)

-10 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 Greenway, FL, Fujioka, K et al. Lancet. Weeks 2010;376(9741):595-605 Change in Selected Items from the Control of Eating Questionnaire at Week 56

Placebo (n=511) How hungry have you felt? Naltrexone 16 mg plus * bupropion (n=471) Naltrexone 32 mg plus * How full have you felt? bupropion (n=471) * 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

*P <.05 vs placebo. Greenway FL, Fujioka, K, et al. Lancet. 2010;376, 595-605. 14 MacMillan M, Cummins K, Fujioka K What weight loss treatment options do geriatric patients with overweight and obesity want to Prevalence of Cravings consider? Obes Sci Pract. 2016 Dec;2(4):477-482

Chart 3: Perceptions 0.9

0.8

0.762 0.7 0.739 0.719

0.6 0.648 0.594 0.573 0.5680.554 0.5 0.543 0.545 0.523 0.512 0.475 0.467 0.473 0.4 0.446 0.416 0.398 0.406 0.376 0.3 0.315 0.273 0.267 0.261 0.2 0.25 0.218 0.228 0.178 0.1

0 A B C D E F G Cravings 1 (<50) 2 (50-65) 3 (>65) Total Adverse Events

Naltrexone ER • Nausea /Bupropion SR 32mg/360 mg • (Forced Titration in studies) N=2545 • Constipation % • Headache • Vomiting • Dizziness • Insomnia • Take second dose late afternoon not late evening • Dry mouth 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*

BLOOM = Behavioral Modification and Lorcaserin for Overweight and Obesity Management. *Only included patients who continued the study past year 1. Smith SR et al. N Engl J Med. 2010;363(3):245–256. Lorcaserin: Those Who Lost ≥ 4.5% Total Body Weight by Week 12 Were Week 52 Responders

Studies 009 and 011, MITT

0 Non-responder: Lorcaserin BID STOP -2.46% -5 % Change -10 -10.22% Responder: Lorcaserin BID -15 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Week

MITT Lorcaserin BID WeekResponder: 12 Completed WeekNon-Responder: 12 Completed Week 52 N = 3097 ≥4.5%Lorcaserin wt loss BID 1369/3097 (44.2%)Lorcaserin BID1083/1369 (79.1%) <4.5% wt loss 1168/3097 (37.7%) 680/1168 (58.2%)

Slide courtesy Dr. Steve Smith; May 10, 2012 FDA Advisory Committee Meeting 20 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 1997-2010

 Sibutramine: % of major adverse  norepinephrine, serotonin, and cardiovascular events dopamine reuptake inhibition 12

11.5  Approved as a weight loss medication in 1997 11

 Published their CardioVascular 10.5 Outcomes Trial in 2010 Subjects with preexisting cardiovascular 10 conditions receiving sibutramine had an increased risk of nonfatal myocardial 9.5 infarction and nonfatal stroke

9  Removed from the market in Placebo Sibutramine 2010 % of major adverse cardiovascular events 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 data Liraglutide 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  At the end of 36 months Percent of patients having a cardiovascular event 12.8% of patients in the Lorcaserin group had a 13.4 Cardiovascular event 13.3 13.3% of patients in the Placebo group had a Cardiovascular event 13.2

13.1

 Lorcaserin group lost more 13 weight (4.2 kg vs 1.4 kg) at one year 12.9 This was a safety trial not a 12.8 weight loss study 12.7  Adverse events: 13 Lorcaserin 12.6 patients vs 4 placebo patients 12.5 had serious hypoglycemia Placebo Lorcaserin Percent of patients having a cardiovascular event

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

Liraglutide GLP-1 hormone Dopamine Nor-epinephrine Motivated reward eating Increase eating Stop Eating

Mesolimbic system Hypothalamus

Dorsal Vagal NPY POMC Complex Hind Brain Stop Eating

GLP-1 Gastrointestinal Track Vagal Afferent fibers Effects of Liraglutide and on Body Weight in Nondiabetic Obese Adults

Astrup A, et al. Lancet. Data are mean (95% CI) for the ITT population 2009;374:1606-1616. Liraglutide 3.0 mgs given to patients after a 6% weight loss

Liraglutide

Liraglutide

Liraglutide Package insert NovoNordisk 2015 (Wadden et al.) Liraglutide 1.8 mgs: Lower Rate of Death1

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

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

Carboxymethylcellulose (CMC) Citric Acid Building blocks are Generally Regarded As Safe (GRAS) by FDA

CMC is cellulose that has been Citric acid is naturally found in citrus oxidized fruits

3D cross-linked matrix

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 loss B- 5% Responders

(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) 58% 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 baseline37 weight and stratification factors. Greenway FL, Arrone LJ, Raben A, Et. Al. A Randomized, Double‐Blind, GLOW, Gelesis Loss Of Weight Placebo‐Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for study; ITT, intention‐to‐treat. Weight Loss, Obesity 2019;27:205-216 Reaching 3% weight loss at 8 weeks predicts responders (sensitivity and specificity > 80%)

0

-2 n=77 -2.1%

-4 Patients treated who -6 lost <3% at 8 weeks Patients treated who -8 lost ≥3% at 8 weeks

-10 n=93

Weight Change from % Baseline, from Change Weight -9.9% -12 0 30 60 90 120 150 Study Day

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

Patients, n (%) Gelesis100 Placebo Difference (n = 223) (n = 211) (95% CI) P-value Any AE probably or possibly 88 (39.5) 64 (30.3) 9.1 (–0.2, 18.2) 0.0557 related Eye disorders 0 (0) 1 (0.5) –0.5 (–3.0, 1.7) 0.4862 GI Disorders 84 (37.7) 58 (27.5) 10.2 (1.0, 19.1) 0.0248 General disorders 1 (0.4) 1 (0.5) –0.0 (–2.6, 2.4) 1.0000 Infections and infestations 2 (0.9) 1 (0.5) 0.4 (–2.2, 3.1) 1.0000 Investigations 3 (1.3) 3 (1.4) –0.1 (–3.3, 3.0) 1.0000 Metabolism and nutrition 0 (0) 4 (1.9) –1.9 (–5.1, 0.6) 0.0551 disorders MSK and connective tissue 2 (0.9) 0 (0) 0.9 (–1.5, 3.5) 0.4992 disorders Nervous system disorders 4 (1.8) 2 (0.9) 0.8 (–2.2, 4.0) 0.6860 Renal and urinary disorders 1 (0.4) 0 (0) 0.4 (–1.8, 2.9) 1.0000 Reproductive disorders 0 (0) 1 (0.5) –0.5 (–3.0, 1.7) 0.4862 Respiratory, thoracic disorders 1 (0.4) 1 (0.5) –0.0 (–2.6, 2.4) 1.0000 Skin and subcutaneous 1 (0.4) 3 (1.4) –1.0 (–4.0, 1.7) 0.3599 disorders 39 • 42 year old female newly diagnosed type 2 diabetes Patient with • Sent by her primary care provider • The patient states she has always been healthy and DM2 is very upset by the diagnosis of “diabetes” and struggling asked to see a specialist • Her only problem in life has been her weight. As with eating early as a teenager she started gaining weight and has struggled her entire adulthood large portions • She is a very successful vice president of a biomedical research start up and has a MD/PhD in of food feeling neurology out of control • 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 • Medications that work thru the GABA system • Topiramate and = 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 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 • dimesylate (L-lysine conjugated to ) • 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 HypothesesVolume 111, 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

Placebo Topiramate 7 6 6.29 5 5.3 4 Mean Binges/wk 3.42 3 2 1 0.31 0 Weeks 0 1 2 4 6 8 10 14

P=.0004. McElroy SL et al. Am J Psychiatry. 2003;160:255-261. Topiramate and BED: Mean Weight Change–ITT

0 1 2 4 6 8 10 14 Weeks 0 -1 -1.16 -2 (2.6 lb) Mean -3 Weight Change -4 (kg) -5 (12.8 lb) Placebo -6 -5.82 Topiramate -7

P=.005. McElroy SL et al. Am J Psychiatry. 2003;160:255-261. 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 % improvement in BES Comprehensive lifestyle categorization management vs Usual care for 26

weeks (82 patients in each group 100 80 completed study) 60 40 • Binge Eating Scale 20 0 • In patients with severe or moderate Binge severity • 91% improved in the Naltrexone/bupropion group • 18% improved in the Usual care % 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 !