The ABCDs of Obesity

Transcription

1 The ABCDs of Obesity Adipose Based Chronic Disease Michael A. Bush, M.D. Clinical Chief, Division of Endocrinology Cedars-Sinai Medical Center Clinical Associate Professor, Geffen School of Medicine, UCLA President, CA-AACE

2 Classification of Weight by BMI with co-morbidities (Must A, et al. JAMA. (1999) 282: ) (NIH. Obes Res. 1998) (World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation presented at: the World Health Organization; June 3-5, 1997; Geneva, Switzerland. Publication WHO/NUT/NCD/98.1) 2

3 CALCULATING BODY MASS INDEX Wt (kg) / Ht (m) 2 MULTIPLY WEIGHT IN POUNDS BY 705 DIVIDE BY HEIGHT IN INCHES DIVIDE BY HEIGHT IN INCHES AGAIN 3

4 Do You Know Your Own BMI? Height Weight (lbs) 4

5 OBESITY IN THE UNITED STATES A Growing Epidemic N/A <10% 10-15% >15% 5

6 Compared with Caucasians, Asians have Higher Levels of Body Fat vs BMI SUBJECTS: Hong Kong Chinese, Indonesians (Malays and Chinese), Singaporean (Chinese, Malays and Indians) Generally, for the same BMI, Asians Body Fat was 3-5% higher compared to Caucasians. Results can be partly explained by differences in body build, i.e. trunk-to-leg-length ratio and slenderness. Differences in muscularity may also contribute. 6 Obesity Reviews (2002), 3:

7 Compared with Caucasians, South Asian Indians have Lower Insulin Sensitivity vs Body Fat South Asians have Lower Insulin Sensitivity for Any Degree of Body Fat Chandalia M, et sl. JCEM (1999)

8 Abdominal Obesity 8

9 Measurement of Body Fat Distribution ASIAN SUBJECTS Women >30 Men >35 9

10 Visceral Fat Distribution Normal vs Type 2 Diabetes Normal Type 2 Diabetes Courtesy of Wilfred Y. Fujimoto, MD. 10

11 Obesity is a Chronic and Multifaceted disease

12 The Natural History of the Development of Obesity in a Cohort of Young U.S. Adults between 1981 and 1998 ( National Longitudinal Study of Youth ) Born in 1964 Born in 1957 McTigue et al. Annals Int Med (2002) 136:

13 OBESE SUBJECTS HAVE DIFFERENT INTESTINAL FLORA 13

14 OBESE SUBJECTS HAVE DIFFERENT INTESTINAL FLORA 14

15 Obesity Evaluation: Take Obesity Seriously Take the time and make it a priority Deal with it as you would other Diseases Adipose-Based Chronic Disease

16 Obesity Meets AMA Criteria for a Disease Impairment of Normal Function Physical impairments Altered physiologic function (inflammation, insulin resistance, dyslipidemia, etc) Altered regulation of satiety in the hypothalamus Characteristic Signs or Symptoms Increased body fat mass Joint pain Impaired mobility Low self-esteem Sleep apnea Altered metabolism Harm or Morbidity Cardiovascular disease Type 2 diabetes Metabolic syndrome Cancer Death AMA, American Medical Association. Mechanick JI, et al. Endocr Pract. 2012;18:

17 Percent of Patients Receiving PCP Advice by Obesity Classification Simkin-Silverman LR et al. Prev Med 2005;40:71-82.

18 The Office Environment An Appropriate Setting for Overweight Patients

19 EVALUATE BMI and COMPLICATIONS Treatment is Complications-Centric 19

20 Take a Disease-focused Medical, Social, and Emotional History MEDICAL CAUSES OF OBESITY Hypothyroidism, Cushing s Syndrome, Depression, Medications MEDICAL/MECHANICAL/EMOTIONAL COMPLICATIONS OF OBESITY SOCIAL AND FAMILIAL FACTORS Clustering, genetics, availability of resources EMOTIONAL FACTORS Psych history, binge eating, comfort eating, eating disorder HISTORY OF OBESITY TREATMENT

21 X YOUR DIET DISCUSS LOTS OF OPTIONS FOR WEIGHT CONTROL DIETITIAN DIET DELIVERED DIET WW/JENNY DIET VLCD DIET MEDICATIONS, LONG-TERM: (Brand:) Qsymia, Belviq, Contrave, Saxenda BARIATRIC SURGERY: Gastric Band, Bypass, Reversals, J-I, Devices 21

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23 TREATMENT OF OBESITY Failure of Diet Therapy My doctor told me I was really in trouble, so I gave up smoking, stopped drinking and started a really good diet... and in 2 weeks I lost 14 days. 23

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25 LOW CARB vs. LOW FAT DIETS IN SEVERELY OBESE SUBJECTS (Avg. BMI 42) Samaha: N Engl J Med (2003), 348:

26 LOW CARB vs. LOW FAT DIET A 1 year Trial with Minimal Professional Contact Foster: N Engl J Med (2003), 348:

27 LOW CARB vs. LOW FAT DIET A 1 year Trial with Minimal Professional Contact Triglycerides HDL Cholesterol Foster: N Engl J Med (2003), 348:

28 LOW CARB vs. LOW FAT DIET A 1 year Trial with Minimal Professional Contact Total Cholesterol LDL Cholesterol Foster: N Engl J Med (2003), 348:

29 Dietary Treatment of Obesity 160 participants were randomly assigned to Atkins, Zone, Weight Watchers, or Ornish diet groups. After 2 months of maximum effort, participants selected their own levels of dietary adherence. Self-rated Adherance Level approximately 25% of participants in each diet group sustained a mean adherence level of at least 6 of 10 Dansinger: JAMA, Volume 293(1).January 5, : 29

30 Dietary Treatment of Obesity Conclusion: future research should be directed to understanding which diets work better for which patients. Dansinger: JAMA, Volume 293(1).January 5, : 30

31 V(ery L(ow) C(alorie) D(iets). 31

32 TREATMENT OF OBESITY Diet with Behavior Modification Wadden: Ann Int Med (1989) 119:

33 MEDICATIONS FOR THE TREATMENT OF OBESITY HISTORICAL PERSPECTIVE s s-90s 1990s 1990s 2000 s 2010s Future approved for chronic Thyroid Hormone weight management Dinitrophenol & Amphetamines Norepinephrine analogues (phentermine) Serotonin effectors (fenfluramine) Dexfenfluramine Serotonin/Norepinephrine (sibutramine) Lipase inhibitor (orlistat) [Wellbutrin, Topomax, Glucophage, GLP1 RAs] [SGLT2i s]; Phentermine/Topiramate ER; Lorcaserin; Bupropion ER/Naltrexone ER; Liraglutide CCK; B3 Agonists; Gene Therapy; PYY 33

34 Phentermine Use Persists in the Marketplace 34

35 MEDICATIONS FOR OBESITY Orlistat Mechanism of Action 35

36 ORLISTAT DOSE RESPONSE CURVE (Based on 100 Grams of Dietary Fat) % Fecal Fat Excretion Data on file. (Ref ) Orlistat Dose (mg) tid 36

37 % change from initial weight MEDICATIONS FOR OBESITY Orlistat: Body Weight Change After 2 Years 0-2 Year 1: Hypocaloric diet Year 2: Eucaloric diet Placebo/Placebo 120/Placebo 120/60 120/ JAMA, Jan 20, 1999 Week 37

38 MEDICATIONS FOR OBESITY Orlistat: Effect on LDL Cholesterol mmol/l LDL-cholesterol 0-2 % Weight loss Orlistat 120 mg tid Placebo p= Week Week Lancet (1998) 352:167 Mildly hypocaloric diet Eucaloric diet 38

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40 MEDICATIONS FOR OBESITY Orlistat: Adverse Effects Adverse Effect Oily spotting Flatus with discharge Fecal urgency Fatty/oily stool Oily evacuation Increased defecation Fecal incontinence Percentage of Patients With Adverse Effects Overall Incidence One Episode Two Episodes Three or More Episodes Data on file, Roche Laboratories, Inc. 40

41 NEWER MEDICATIONS FOR WEIGHT LOSS COMBINATION PHENTERMINE/TOPIRAMATE

42 from the PI Indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m 2 or greater or 27 kg/m 2 or greater in the presence of at least one weightrelated comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia If <3% weight loss after 12 weeks on usual dose, either discontinue medication or advance to maximum dose If <5% weight loss after 12 weeks on maximum dose, then discontinue the medication (to discontinue take every other day for one week) 42

43 Phentermine/Topiramate ) CONQUER Study: Weight Loss at 1 Year Lancet (2011). 377:

44 Weight Loss with Phentermine/Topiramate ER Delays the Progression to Diabetes Subjects with Pre-Diabetes or Metabolic Syndrome 44

45 Phentermine/Topiramate ER ) Adverse Effects Increase in heart rate or blood pressure Dry mouth, dysgeusia, constipation Insomnia, irritability, anxiety Disturbances in attention, lack of concentration CONTRA-INDICATIONS Pregnancy Glaucoma 45

46 PHENTERMINE/TOPIRAMATE ER Initiating Treatment

47 LORCASERIN FOR WEIGHT LOSS Lorcaserin (Belviq) is a selective 5-HT 2C (Serotonin) Receptor Agonist. 5-HT 2C receptors are located almost exclusively in the brain in many sites, including the hypothalamus. Clinical Use Schedule IV Controlled Substance 10 mg twice daily (Belviq XR is 20mg once a day) Discontinue if 5% weight loss is not achieved within 12 weeks 47

48 Lorcaserin Adverse Events Event occurring in 5% of patients and more frequently than with placebo, % Lorcaserin 10 mg BID (N=3195) Placebo (N=3185) Headache Upper respiratory tract infection Nasopharyngitis Dizziness Nausea Fatigue Urinary tract infection Diarrhea Back pain Constipation Dry mouth Belviq (lorcaserin HCl) prescribing information. Woodcliff Lake, NJ: Eisai Inc.;

49 Lorcaserin Treatment in Obese or Overweight Subjects % Subjects with 5% or 10% Weight Loss 49

50 Combined Lorcaserin + Phentermine Treatment for Weight Loss NOT FDA APPROVED! 50

51 Patients with A1C 6.5% (%) Effect of Lorcaserin on Progression to T2DM Proportion of BLOOM and BLOSSOM Patients With Newly Diagnosed Diabetes After 52 Weeks of Treatment P=0.003 Lorcaserin hydrochloride briefing document for FDA Advisory Committee. Woodcliff Lake, NJ: Eisai Inc.; Available at: ommittee/ucm pdf. 51

52 Bupropion/Naltrexone ER (Contrave) Bupropion: stimulates POMC neurons Has been used for binge activities, smoking cessation Naltrexone: Blocks POMC auto-inhibition Presumably works at the hedonistic centers of the brain Adverse Effects: -- nausea, constipation -- headache, paresthesias -- dry mouth

53 Bupropion/Naltrexone ER (Contrave) 5%, 10%, and 15% Weight Loss LOCF COMPLETERS Greenway FL, Fujioka K, Plodkowski RA et al. Lancet. 2010; 376:

54 Early Weight Loss (week 16) Predicts Weight Loss Success at 1 year Plodkowski RA, Walsh B, Berhanu, P et al. Presentated at Cleveland Clinic Obesity Summit 10/2/2015.

55 VICTOZA AND SAXENDA What s the Difference? VICTOZA Liraglutide Indicated for Type 2 DM Doses range from 0.6 (starter dose) to 1.2 to 1.8 mg Pen contains 3 ml, 6 mg/ml 2 Pens/month for 1.2 daily, 3 Pens/month for 1.8 daily. Slows stomach emptying, reduces appetite, improves pancreatic function May cause nausea SAXENDA Liraglutide Indicated for Obesity Doses range from 0.6 (starter dose) to 1.2, 1.8, 2.4, & 3.0 mg Pen contains 3 ml, 6 mg/ml 5 Pens/month for 3.0 daily. Slows stomach emptying, reduces appetite May cause nausea 55

56 Weight Loss with Liraglutide (Saxenda) 5% and 10% Weight Loss Pi-Sunyer X, Astrup A, Fujioka K et al. NEJM.2015; 373(1):11-22.

57 Liraglutide After Successful Low Calorie Diet -5.8% -5.6% -5.4% The SCALE Maintenance randomized study. Int J Obesity Nov;37(11):

58 MEDICATIONS FOR CHRONIC WEIGHT MANAGEMENT Composite of Completer Data Plodkowski RA, McGarvey ME, Nguyen QT et al. Federal Practitioner. In press Jan 2015.

59 Weight Loss at 1 Year with High-Intensity Lifestyle or Pharmacotherapy Combined with Low Level Counseling. Heymsfield SB, Wadden TA. N Engl J Med 2017;376:

60 Obesity Drugs Mechanisms of Action Kim et al., Clin. Pharm. Ther 2013

61 Unrealistic Goals: Average Fashion Model vs Average Woman* Height Weight BMI Average Fashion Model 5' 9" 110 lb 16.3 Average Woman 5' 4" 142 lb 24.3 BMI = body mass index. *Written communication from TA Wadden, PhD, July

62 Benefits of Modest Weight Loss in Patients With Hypertension, Hyperlipidemia and Diabetes Each kg of weight loss lowers blood pressure by 2.5/1.7 mm Hg lowers total cholesterol by 1.93 mg/dl lowers LDL cholesterol by 0.77 mg/dl lowers triglycerides by 1.33 mg/dl increases survival in Type 2 diabetes by 3-4 months Schotte et al. Arch Intern Med. 1990;150: Dattilo et al. Am J Clin Nutr. 1992;56: Seim et al. Fam Pract Res J. 1992;12: Lean et al. Diabet Med. 1989;7: Wing et al. Arch Intern Med. 1987;147:

63 GOAL WEIGHT IN THE TREATMENT OF OBESITY 63

64 TREATING OBESITY IN YOUR PRACTICE With the increase in obesity and co-morbid conditions, obese patients need access to quality care Small differences in approach and attitude related to weight and weight loss can have a huge impact The treatment of obesity can be easily integrated into any primary care setting. Increase your communication with patients who are obese and take aggressive steps to treat this serious disease.