Obesity: Pharmacologic and Surgical Management

Transcription

1 Obesity: Pharmacologic and Surgical Management ADRIENNE YOUDIM, MD, FACP ASSOCIATE PROFESSOR OF MEDICINE, UCLA ASSISTANT PROFESSOR OF MEDICINE, CEDARS SINAI MEDICAL CENTER JANUARY 2018

2 Defining Obesity Classification BMI (kg/m 2 ) Underweight <18.5 Normal Overweight Obese Morbidly obese >40 Super obese >50

3 Medical Complications of Obesity Pulmonary disease asthma obstructive sleep apnea hypoventilation syndrome Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Gall bladder disease Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis Skin Gout Idiopathic intracranial hypertension Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Phlebitis venous stasis

4 Complexity of Energy Homeostasis

5 Weight Loss Effect on Ghrelin Sumithran P. NEJM 2011;365(17):1597.

6 Hunger and Desire to Eat Following Weight Loss Sumithran P. NEJM 2011;365(17):1597

7 1996 FDA Draft Guidelines for the New Drug Development in Obesity Primary Efficacy Endpoints: At least 5% difference in mean % body weight between drug and placebo At least 35% of treated subjects lose at least 5% base line body weight compared to placebo Secondary Efficacy Endpoints: Blood pressure and pulse Lipoprotein lipid levels Fasting glucose and insulin HbA1c Waist Circumference

8 Impact of Weight Loss on Risk Factors HbA1c Blood Pressure Total Cholesterol HDL Cholesterol Triglycerides ~5% Weight Loss %-10% Weight Loss Wing RR et al. Arch Intern Med. 1987;147: Mertens IL, Van Gaal LF. Obes Res. 2000;8: Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S. 4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:

9 Orlistat-Mechanism of Action Intestinal Lumen Mucosal Cell Orlistat TG MG FA Micelle

10 Sympathomimetics Block Neuronal Monoamine Reuptake (Phentermine) XS = Monoamine S = Sympathomimetic

11 Phentermine Adult dosage: mg Mean weight loss: 6.3 kg ( kg) Adverse reaction: elevated BP/HR, insomnia, Anxiety/irritability Contraindicated: CAD, angina, hyperthyroid, glaucoma, uncontrolled hypertension, substance abuse Drug-Drug reactions: MAOIs, tricyclics, SSRI, Inhaled anesthetics Schedule Class IV Drug Approved for short-term use (3 months)

12 BP/HR as a function of Weight Loss in Subjects on Phentermine Hendricks. Obesity 2011.

13 Phentermine/Topiramate Combination of controlled release phentermine and topiramate Dosage: 3.75/23 mg x 14 days 7.5/46 mg Use for 3 months Must achieve 3% weight loss achieved in 12 weeks otherwise discontinue or escalate dose 15/92 mg if 5% weight loss not achieved discontinue

14 Phentermine/Topiramate Contraindicated: CAD, pregnancy, glaucoma, MAOI use, Side Effect Profile: paraesthesia, dizziness, insomnia, constipation, and dry mouth, birth defects, metabolic acidosis Monitoring: **baseline and monthly BHCG, baseline and periodic lytes/cr Online training recommended

15 Conquer: Combination therapy with Phentermine/Topiramate.Lancet ;377(9774):

16 Subjects Achieving 5-20% Weight Loss Garvey et al. Am J Clin Nutr

17 Gadde KM. Lancet 2011;377:1341

18 GLP1 Physiology Drucker et al. Lancet 2006

19 Liraglutide Dosage: 0.6 mg Titration increase by 0.6 mg to full dose of 3.0 mg over 4 weeks Discontinue if >4% weight loss not achieved by 16 weeks Contraindicated: personal or family history of medullary thyroid carcinoma or MEN2 Warnings: thyroid ca, acute pancreatitis, GB disease, hypoglycemia, increase in HR, ARF, suicidal ideation Adverse reactions: nausea, hypoglycemia, diarrhea, constipation, vomiting, dry mouth, headache, fatigue, dizziness, abdominal pain, dyspepsia.

20 Wadden et al. Int Jour of Obes

21 Combination Stimulatory of POMC and Antagonism of Opiod R (bupropion/naltrexone) Billes et al. Pharmacol Res. 2014

22 Bupropion and Naltrexone Dosage: 16/180 mg (2 tablets) bid Titration starting at 8/90 mg once daily to max dose over 4 weeks Discontinue if 5% weight loss not achieved by 12 weeks Contraindicated: uncontrolled HTN, seizure d/o, bulimia, anorexia, opioid or opioid antagonist use, abrupt etoh discontinuation, MAOI Adverse reactions: nausea, headache, constipation, vomiting, dry mouth Warnings/Precautions: SI, seizures, elevations in blood pressure and HR, angle closure glaucoma, hepatotoxicity Drug interactions: MAOI, Opioids, Drugs metabolized by CYP2D6

23 Combination Pharmacotherapy with Bupropion and Naltrexone Apovian. Obesity 2013(21):935.

24 Serotonergic Agonist (Lorcaserin)

25 Lorcaserin Dosage: 10 mg bid Discontinue if 5% weight loss not achieved by 12 weeks Contraindicated: pregnant and nursing mothers Warnings and Precautions: NMS, valvular disease, phtn, psychiatric d/o, hypoglycemia in diabetics Adverse reactions: priapism, attention or memory disturbance, headache, dizziness, dry mouth Drug interactions: Serotonergic drugs: SSRIs, monoamine oxidase inhibitors (MAOIs), triptans, bupropion, dextromethorphan, St. John s Wort

26 Bloom: Weight Loss with Lorcaserin 2.2 kg= kg=12.7 Smith et al. NEJM 2010;363(3):245-56

27 Comparison of Efficacy and AE of Pharmacological Treatments for Obesity Khera Jama 315(22):2016;

28 Gastric Bypass

29 Changes in Ghrelin following RYGB MWL Obese controls RYGB Cummings. NEJM. 2002:346(21)

30 Changes in GLP-1 post RYGB Borg. British Journal of Surgery (2) Morinigo. Journal of Clinical Endocrinology and Metabolism. 2006:91(5)

31 Sleeve Gastrectomy

32 Insulin Sensitivity following Weight Loss Surgery Peterli R. Ann Surg. 2009; 250:

33 Weight Loss following Bariatric Surgery Adams et al. NEJM. 2017;377(12):1143.

34 Mortality and Bariatric Surgery Adams. NEJM 2007;357:

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