Disclosures Treatment of : • None Diets, Drugs and Surgery

Michelle Guy, MD Professor Clinical Medicine University of California San Francisco Diplomate American Board of

Questions 1 Objectives • Understand provider barriers to treating patients with and True or False—Answer the following question for yourself obesity • Know the classifications of obesity I have at some point during my career exhibited or expressed weight • Understand lifestyle modifications for bias, either subtle or overt, towards a patient with overweight or • Know which medications promote obesity. • Review the FDA approved medications for weight loss • Review the common weight loss surgeries 1) True or Yes 2) False or No Weight Bias in Healthcare Weight Bias • Negative attitudes toward persons with overweight or obesity • Study of 2400 women with obesity • Can be subtle or overt • 69% reported doctors were a source of weight bias • Can be verbal, physical or relational • 52% reported being stigmatized by a doctor multiple times • Stereotypes can lead to: • Patient factors • Stigmatized patients are more vulnerable to depression, anxiety or low self‐esteem • stigma • May feel less motivated to adopt lifestyle changes • rejection • May avoid or cancel appointments • prejudice • Provider factors, as BMI increases: • discrimination • Report less desire to help patients • More likely to report that treating patient is a waste of time • Express less respect for patient

Obesity Action Coalition, www.obesityaction.org Obesity Action Coalition, www.obesityaction.org

2 Mortality and Morbidity of Obesity (BMI)kg/m

• Greater BMI is associated with Normal Overweight increased rate of death from all causes and cardiovascular 18.0‐24.9 25.0‐29.9 disease • There are currently over 200 comorbidities associated with obesity Class I Class II Class III • Even modest weight loss, 5% to 30.0‐34.9 35.0‐39.9 > 40.0 10%, improves comorbidities Whitlock G, Lewington S, Sherliker P, et al. Body‐mass index and cause‐specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373:1083. Illustration used with the permission of Elsevier Inc. All rights reserved. Current Treatment Options for Obesity Options for Obesity Question 2 Surgery (In order of lowest risk/cost and potency): LAGB

Obesity Algorithm®. ©2016-2017 Obesity Medicine Association. Reference/s: [1]

Dietary Interventions Exercise Interventions

Caloric Restriction, Reduce Energy Intake, Caloric Deficit • Exercise has benefits independent of weight loss self monitoring . Attenuates diet‐induced loss of muscle mass eliminate liquid calories . Improves physical functioning stimulus control . Reduces risk of heart disease, stroke, and premature death portion control intermittent fasting • Exercise is important for the primary prevention of obesity • Exercise alone or added to diet has only modest effect on weight loss Macronutrient composition does not predict weight loss • Studies have not shown additional benefits with use of activity Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and trackers heart disease risk reduction: a randomized trial. Dansinger, JAMA 2005;293(1):43 • Exercise is important for preventing weight regain . At least 30 minutes 5 days a week (150 minutes per week) The diet a patient can adhere to the longest, is the best diet for that patient Case Question 3

Mr Earl is a 45 y/o man who is concerned about his weight (BMI How many of his medications 1) Glyburide 38) and would like your help “shedding a few pounds” may be contributing to Mr. 2) Glargine Insulin Earls’ weight gain? 3) Lisinopril PMHx: Diabetes type 2, HTN, depression, neuropathic low back pain 4) Atenolol A) All 8 5) Bupropion Medications: Glyburide, Glargine Insulin, Lisinopril, Atenolol, B) 7 6) Paroxetine Bupropion, Paroxetine, Amitriptyline, Gabapentin C) 6 7) Amitriptyline D) 5 8) Gabapentin How many of the above medications may be contributing to this patient’s weight gain? E) 4

Medications That Promote Weight Gain Medications That Promote Weight Gain CLASS GENERIC NAME POSSIBLE ALTERNATIVES Cardiovascular—Beta Propranolol, Atenolol, Carvedilol, ACE Inhibitors • This is just part of the story Blockers Metoprolol

• Review timing of weight gain and initiation of medications Cardiovascular—Calcium Nifedipine, Amlodipine, Verapamil • Consider starting alternatives to weight promoting medications in Channel Blockers Felodipine patients with overweight and obesity Diabetes Insulin, Sulfonylureas, Metformin, Glucagon‐like • Varying mechanisms responsible for weight gain: fluid retention, Thiazolidinediones, pepetide‐1 agonists, Sodium increased appetite, increased deposition of Meglitinides glucose co‐transporter 2 inhibitors, Alpha glucosidase inhibitors Hormones Glucocorticoids, Estrogens, Progestins, Testosterone

Alpha‐adrenergic agonists Prazosin, Doxazosin, Dutasteride, Proscar Terazosin Medications That Promote Weight Gain Anti‐Obesity Medications CLASS GENERIC NAME ALTERNATIVE MEDICATIONS

Anti‐seizure Carbamazepine, Lamotrigine, Topiramate, • Diet, exercise and behavioral modification must accompany all Gabapentin, Valproate Zonisamide adjunct treatments Antidepressants Amitriptyline, Doxepin, Bupropion, Sertraline, • Consider addition of anti‐obesity medications in patients who: Paroxetine, Mirtazapine Duloxetine • have not been successful with diet and exercise • and BMI > or = 27 and obesity related comorbidities or BMI > 30 Antipsychotics Clozapine, Olanzapine, Aripiprazole, Haloperidol • need adjunct treatment for weight regain Risperidone, Lithium • Anti‐obesity medications have only modest effects on weight Hypnotics Diphenhydramine Trazodone, • Goal is to modify or improve comorbid conditions Benzodiazepines Chemotherapies Tamoxifen, Methotrexate, • 5‐10% weight loss may improve both metabolic and fat mass disease Aromatase Inhibitors Obesity Algorithm®. ©2016‐2017 Obesity Medicine Association.

Anti‐Obesity Medications Conquer Study MEDICATION LENGTH OF TRIAL TOTAL WEIGHT LOSS Phentermine HCL/Topiramate ≥1 year ‐10.2 kg extended release (Qsymia) • 1‐year placebo‐controlled trial of 2487 patients with 2 or more Phentermine 13 weeks ‐6.4 kg morbidities Naltrexone HCL/Bupropion HCL ≥1 year ‐6.1 kg • 61% patients completed 1 year of treatment with absolute body weight extended release (Contrave) change: Orlistat (Xenical and Alli) ≥1 year ‐5.3 kg • −1·8 kg placebo • −9·9 kg phentermine 7·5 mg plus Lorcaserin (Belviq) 1 year ‐5.8 kg topiramate 46·0 mg Liraglutide (Saxenda) 24 weeks ‐2.8 kg • −12·9 kg phentermine 15·0 mg plus topiramate 92·0 mg Metformin 1 year ‐2.8 kg

LeBlanc ES, O'Connor E, Whitlock EP, et al. Effectiveness of primary care‐relevant treatments for obesity in adults: A systematic evidence review for the U.S. Preventive Services Gadde, KM. CONQUER. Lancet 2011;377:1341‐52 Task Force. Ann Intern Med 2011; 155:434. MEDICATION MECHANISM OF ACTION CONTRAINDICATIONS, SIDE EFFECTS and PEARLS

FDA Approved Anti‐Obesity Medications Phentermine Norepinephrine‐releasing agent Not recommended for patient with heart disease or uncontrolled HTN Tachycardia, Insomnia, Overstimulation, Approved for short‐ term use, DEA schedule IV • If < 5% weight loss after 12‐16 Anti‐obesity Medications Phentermine/Topiramate Norepinephrine‐releasing agent, As above / Avoid in patients with glaucoma or CKD, can cause weeks discontinue medication Approved in 1999 or Before (Qsymia) GABA receptor modulation agent metabolic acidosis, increased creatinine, dry mouth, paresthesia

• If medication is effective, • Phentermine Naltrexone/Bupropion Opioid antagonist/ Dopamine and Uncontrolled HTN, seizure disorders, anorexia/bulimia, chronic continue longterm • Orlistat (Xenical and Alli) (Contrave) norepinephrine reuptake inhibitor opioid use, headache, constipation, insomnia

• Do not administer to women Anti‐obesity Medications Lorcaserin (Belviq) 5HT2c receptor agonist Co‐administration with serotonergic agents has not been who are pregnant or trying to established, may cause serotonin syndrome, headache, fatigue, Approved in 2012 and Beyond cough, memory disturbance and hypoglycemia in diabetics become pregnant • Lorcaserin (Belviq) Orlistat (Xenical, Alli) Pancreatic and gastric lipase inhibitor Oily discharge from the rectum, flatus, fecal incontinence, • Consider side effect profile and • Phentermine HCL/Topiramate extended cholelithiasis , kidney stones (oxalate), liver injury, decrease fat‐ dual use in choosing medication release (Qsymia) soluble vitamin absorption • Naltrexone HCL/Bupropion HCL extended Liraglutide (Saxenda) Glucagon‐like peptide‐1 (GLP‐1) Injectable, dose must be titrated over 4 weeks given significant release (Contrave) receptor agonist dose dependent nausea and vomiting, diarrhea, hypoglycemia, • Liraglutide (Saxenda) increased lipase. Contraindicated in personal or family hx of MEN2 or thyroid cancer

Question 4 Who is Eligible for Surgery?

Which of these patients is the least ideal candidate for ? 1) BMI > 40 Or BMI 35-40 & Comorbidity 1) 30 y/o man BMI 42 but no obesity related comorbidities 2) 62 y/o woman BMI 38 and severe urinary incontinence And 3) 28 y/o man BMI 52 who quit smoking 2 months ago 2) Must have tried and failed other medically 4) 39 y/o woman BMI 43 who plans pregnancy in next year managed weight-loss programs 5) 55 y/o man BMI 35 and poorly controlled

1991 NIH Consensus Panel Recommendations Contraindications to Bariatric Surgery Question 5

High Surgical Risk Which intervention can lead to the largest percentage of • Severe cardiac disease with high risk for anesthesia sustained excess weight loss? • Severe coagulopathy 1) Sleeve Gastrectomy (SG) Poor Post-op Compliance 2) Diet and Exercise • Untreated major depression or psychosis 3) Laparoscopic Adjustable Gastric Banding (LAGB) • Binge-eating disorders 4) Biliopancreatic Diversion with Duodenal Switch (BPD/DS) • Current drug or alcohol abuse 5) RNY Gastric Bypass (RYGB) • Inability to comply with post op diet and supplementations

Laparoscopic Weight Loss Surgery Lap BandSleeve Gastrectomy Gastric Bypass Laparoscopic Adjustable Gastric Banding (LAGB)

Restrictive Only, Not Metabolic Sleeve Gastrectomy (SG) Ideal Candidate Restriction/Resection and Metabolic • BMI 30*-40 kg/m2 Ideal Candidate • Needs to lose 50-100 pounds BMI 35‐55 kg/m2 Benefits Needs to lose 80‐150 lbs • Fewer early risks than other procedures Benefits • One hour procedure Excess Weight Loss 70‐90% • Fully Reversible/Removable 1‐2 hour procedure • Lowest risk of vitamin deficiencies Recovery ranges from days to weeks Considerations/Risks Patients report early and lasting fullness • Excess Weight Loss (EWL) 50% Intestines stay intact—No malabsorption • 10-year removal or reoperation rate is >25% May cure diabetes • Slower weight loss (1-2lbs/week) compared to other surgeries Considerations/ Risks • Appetite suppression may be difficult to achieve Removal of a portion of the stomach is • Least effective for resolving diabetes permanent The remaining pouch may expand over time *FDA approved LAGB for pts w/ BMI Class I obesity and Type 2 diabetes or other obesity related comorbidity

Roux en Y Gastric Bypass (RNY or Bypass or RYGB) Biliopancreatic Diversion w/ or Restrictive/Malabsorptive & Metabolic w/o Duodenal Switch (BPD/DS) Most common procedure performed Restriction, Resection, Malabsortive & Metabolic Ideal Candidate Ideal Candidate • BMI 35-55 kg/m2 BMI > 60 kg/m2 • Needs to lose 100- 150 + lbs Poorly controlled diabetic • May have severe or prolonged medical conditions Benefits Benefits Has the highest cure rate for diabetes • Excess Weight Loss 70-90% Excess Weight Loss 80‐90% • 2 hour procedure 3‐4 hour procedure • Recovery of days to weeks 200‐400 cal lost from malabsorption • Very effective for curing diabetes • Approximately 100-200 calories per day lost Considerations/Risks through malabsorption Not offered by most surgeons • Procedure is reversible Stomach removal is permanent but bypass may be reversed Considerations/Risks Highest risk for vitamin and protein deficiencies, • Greater risk for vitamin deficiencies diarrhea and intestinal blockages • Dumping syndrome • Smoking, EtOH, NSAIDS use may lead to ulcers Take Home Points References

• Consider what weight biases you may have • Obesity Action Coalition, www.obesityaction.org • Obesity Algorithm® ©2016‐2017 Obesity Medicine Association • Diet, exercise and behavior modification is the cornerstone of obesity • Whitlock G, Lewington S, Sherliker P, et al. Body‐mass index and cause‐specific mortality in treatment 900,000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373:1083 • Gadde, KM. CONQUER. Lancet 2011;377:1341‐52 • Consider alternatives to medications that promote weight gain • Apovian et al Guidelines on Pharmacological J Clin Endocrinol Metab, February 2015, 100(2):342–362 • Anti‐obesity medications may add 2.8 to 10.2 kg of weight loss vs • 1991 NIH Consensus Panel Recommendations for Bariatric Surgery placebo • LeBlanc ES, O'Connor E, Whitlock EP, et al. Effectiveness of primary care‐relevant treatments for obesity in adults: A systematic evidence review for the U.S. Preventive Services Task Force. Ann • 5‐10% weight loss may improve both metabolic and fat mass disease Intern Med 2011; 155:434. • 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report • Bariatric surgery can have significant improvement on weight and of the American College of Cardiology/American Heart Association Task Force on Practice obesity related conditions for those patients who are good candidates Guidelines and The Obesity Society. J Am Coll Cardiol 2013 Nov 7