Overview of the Pharmacologic & Surgical Treatment for Obesity

Transcription

1 Overview of the Pharmacologic & Surgical Treatment for Obesity Christopher D. Still, DO, FACN, FACP. FTOS Medical Director, Center for Nutrition & Weight Management Director, Geisinger Obesity Research Institute Geisinger Health Care System Danville, Pennsylvania May 25, 2018 Components of an Effective Obesity Management Program Surgery or Medications Behavior Modification Physical Activity Diet Wadden TA, Foster GD. Behavioral treatment of obesity. Med Clin North Am. 2000;84: Stumbo, PH, et. al. Dietary and medical therapy of obesity. Surg Clin N Am 85(2005) Currently Available Treatments: Risks and Efficacy Lower risk Diets VLCD Pharma Lower efficacy Devices* Lap band Sleeve Roux en Y bypass BPD DS Higher efficacy Higher risk *Gastric sleeve and vagal stimulator under phase 3 study. SVLCD: very low calorie diet Jensen. MD, Ryan DH, et al. J Am Coll Cardiol. 2013;pii:S (13) Accessed May 12,

2 DIET INDIVIDUAL INFLUENCES Genetic/Epigenetic Expenditure Intake Metabolism ETOH Activity Fat Stable TEF Carb Protein Basal Metabolic Rate ETOH = ethyl alcohol; TEF = thermic effect of food Which Diet is Best? Low Calorie Low Glycemic Low Fat Low CHO 6 2

3 What is the Relationship Between Macronutrient Proportion and Body Weight in Adults? There is strong and consistent evidence that when calorie intake is controlled, macronutrient proportion of the diet is NOT related to losing weight No optimal macronutrient proportion was identified for enhancing weight loss or weight maintenance Weight and Metabolic Outcomes After 2 Years on a Low CHO vs Low-Fat Diet A Randomized Trial Predicted absolute mean change in body weight for participants in the low-fat and low-carbohydrate diet groups, based on a random-effects linear model. Error bars represent 95% CIs. Foster, GD, et al. Ann Intern Med. 2010;153(3): doi: / Meta Analysis: Comparison of Weight Loss Among Diet Programs in Overweight and Obese Adults 48 randomized trials; N=7,286 overweight or obese persons 25 of the studies examined weight loss at one year; n=5,000 Low-fat diets Ornish, Rosemary Conley ~ 60 kcal CHO / 10-15% kcal PRO / 20% kcal FAT Low-carb diets Atkins, South Beach, Zone 40% kcal CHO / 30% kcal PRO / 30-55% kcal FAT 6 Months 12 Months 7.99 kg 7.27 kg 8.73 kg 7.25 kg CONCLUSION Weight loss differences between individual diets were small Any diet a patient will adhere to in order to lose weight is best 9 Johnston BC, et a. JAMA. 2014;312(9):

4 Effects of Low-Carbohydrate and Low-Fat Diets Randomized trial, 119 completers, 12 months Conclusion: n= 60/82; low-fat group Low carbohydrate <30% fat daily (<7% diet was sat fat) more 55% effective from carbs for weight loss and cardiovascular risk factor reduction n=59/79; than low-carb the low fat group diet <40 gm/day 1.8 kg 3.5 kg P= kg Total HDL Cholesterol Ratio % Fat Mass Triglyceride Level P= % P= mmol/l ( 14.1 mg/dl) P= Bazzano LA, et al. Ann Intern Med. 2014;161(5): *P< 0.05 for between-group difference Rule of Thumb for Calculating Current Caloric Needs 8 calories per pound for women, no correction for exercise 250 lb. women = ~2000 kcal/day upon presentation Recommend 1500 kcal/day meal plan 10 calories per pound for men, no correction for exercise 300 lb. man = ~3000 kcal/day upon presentation Recommend 2500 kcal meal plan Most Popular Commercial Programs With an Evidence Base to Evaluate Weight Watchers Two diet options, expanded from classic points program Low cost (as little as $12 per week) Choose between webbased and group setting Lay counseling Nutrisystem Provides food and telephone counseling ~$280-$370 per month Shelf-stable dry or frozen foods with supplemental fruits and vegetables Jenny Craig Provides food and in-person or telephone counseling ~$500-$650 per month Shelf-stable dry or frozen foods with supplemental fruits and vegetables 4

5 Online Programs INTERNET-DELIVERED PROGRAMS Most successful internet programs, that provide weekly feedback to participants, will induce weight losses of ~ 2/3 the size of those achieved by traditional on-site behavioral programs Wadden TA, et al. Circulation. 2012;125(9): Bottom-line on Diets Reduce Calories by ~ 500 kcal/day Stick with it!! Goal weight loss: 5-10% Increments goals 5

6 Visceral Adipose Tissue: Associated with Cardiometabolic Risk Subcutaneous Adipose Tissue Subcutaneous Adipose Tissue Visceral Adipose Tissue VAT 10% Weight Loss = 30% VAT Loss Visceral Adipose Tissue VAT Deterioration Lipid profile Improvement Impaired Insulin sensitivity Blood insulin Blood glucose Risk markers for thrombosis Inflammatory markers Improved Abdominal obesity Increased waist circumference Impaired Endothelial function Improved Increased Risk Low After weight loss Reduced waist circumference Adapted from: Després J, et al. BMJ. 2001;322: The Power of Monitoring and Accountability 18 Self-monitoring Frequent Weigh-Ins 6

7 Water Intake AVOIDANCE OF Regular sodas Fruit juices Caloric beverages Activity Intake ETOH Fat INDIVIDUAL INFLUENCES Genetic/Epigenetic Stable Expenditure Metabolism Activity TEF Carb Protein Basal Metabolic Rate 7

8 The Lifestyle Approach 10 Noon-time jog Sedentary Exercise Lifestyle Activity Walk to bus stop After-dinner walk Time (hours) Blair SN, et al. Med Exerc Nutr Health. 1992;1: Tracking Physical Activity Nike FUEL JawBone Accelerometer Fitbug BodyMedia Fitbit PHARMACOTHERAPY 24 8

9 Criteria for Using FDA Approved Medications BMI: < >35 >40 Underweight Normal Overweight Obesity I Obesity II Obesity III BMI >27 kg/m 2 with 1 comorbidity BMI >30 kg/m 2 with no comorbidities 25 FDA Approved Pharmacotherapy Options for the Treatment of Obesity Phentermine (and other noradrenergic agents) Orlistat (Xenical/Alli) Phentermine/topiramate ER (Qsymia) Lorcaserin (Belviq) Bupropion SR/Naltrexone SR (Contrave) Liraglutide 3.0mg (Saxenda) Phentermine Sympathomimetic amine, NE release Blunts appetite Approved in 1959 for short term use, schedule IV Dosing: mg qam; use lowest effective dose Contraindications: pregnancy, nursing, MAOIs, glaucoma, drug abuse history, hyperthyroidism Relative contraindications: uncontrolled HTN, tachycardia, history of CAD, CHF, stroke, arrhythmia Phentermine [package insert]. Cranford, NJ: Alpex Pharma SA : Munro JF, et al. Br Med J. 1968;1(5588):

10 Lorcaserin Selective 5HT 2c receptor agonist; stimulates α MSH production from POMC neurons, activating MC4R Increases satiety Approved in 2012 for long term use, schedule IV Single dose: 20 mg XR qday; discontinue if less than 5% weight loss after 12 weeks of use Contraindications: pregnancy Warnings: co administration with serotonergic or antidopaminergic agents, valvular heart disease, psychiatric disorders (euphoria, suicidal thoughts, depression), priapism, risk of hypoglycemia with some diabetes medications BELVIQ [Prescribing Information]. Woodcliff Lake, NJ: Eisai Inc; Phentermine/Topiramate ER Phentermine: sympathomimetic amine; blunts appetite Topiramate: increases GABA activity, carbonic anhydrase inhibitor, other actions; prolongs satiety Approved in 2012 for long term use; schedule IV Treatment ( recommended dose): 7.5/46 mg qam; max dose: 15/92 mg Contraindications: pregnancy, glaucoma, MAOIs, hyperthyroidism Warnings: fetal toxicity, increased HR, suicidal thoughts, mood disorders, sleep disorders, cognitive impairment, metabolic acidosis, creatinine elevations, hypoglycemia with some diabetic medications Phentermine and topiramate extended-release [package insert]. Mountain View, CA : Vivus; Bupropion SR/Naltrexone SR Approved by FDA September 10, 2014 Bupropion: dopamine/noradrenaline reuptake inhibitor; activates POMC neurons in the hypothalamus, leading to decreased appetite Naltrexone: opioid receptor antagonist; blocks autoinhibition of POMC neurons and amplifies the effect of bupropion Dosing: Week 1: 1 tab (8mg/90mg) in AM Week 2: 1 tab BID Week 3: 2 tabs in AM; 1 in PM Week 4+: 2 tabs BID Consider discontinuation if <5% weight loss after 12 weeks Greenway, et al. Obesity. 2009;17:

11 Liraglutide 3.0 mg Glucagon like peptide 1 (GLP 1) receptor agonist Multiple actions; effect on weight is primarily via POMC neurons FDA approved 3.0 mg/day for primary indication of obesity Baggio LL, et al. J Clin Invest. 2014;24(10): ; Secher A, et al. J Ciin Invest. 2014;124(10): Choosing Between Options 100% 75% 50% 25% 0% >5% BWL >10% BWL Contraindications & Cautions Clinical scenario Elevated seizure risk h/o recurrent kidney stones h/o glaucoma Uncontrolled hypertension Coronary artery disease Moderate severe renal impairment Moderate severe hepatic impairment SSRI use Avoid/caution Naltrexone SR/bupropion SR Phentermine/Topiramate ER, orlistat Phentermine/Topiramate ER Naltrexone SR/bupropion SR Phentermine Do not exceed half dose: Phentermine/Topiramate ER, Naltrexone SR/bupropion SR Caution: liraglutide 3.0 mg, lorcaserin Do not exceed half dose: Phentermine/Topiramate ER Do not exceed ¼ dose: Naltrexone SR/bupropion SR Caution: liraglutide 3.0 mg, lorcaserin Caution: lorcaserin See package inserts 11

12 Dual Benefits Obesity and Smoking Depression Migraines Diabetes Chronic constipation Elevated LDL Consider, but not explicitly approved Naltrexone SR/bupropion SR Naltrexone SR/bupropion SR Phentermine/Topiramate ER Liraglutide 3.0 mg Orlistat Orlistat Slide courtesy of S. Kahan Thoughts on Pharmacotherapy Treatment of obesity with pharmacotherapy as an adjunct to lifestyle modification is a valuable option for obesity treatment Several options are available and FDA approved Understand potential benefits and risks of agents when planning treatment Different patients respond to different medications If one option doesn t work well, consider others REALISTIC EXPECTATIONS Bariatric Surgery Criteria BMI: < >35 >40 With 1 severe obesityassociated comorbidity (e.g., diabetes or OSA) With no comorbidities 12

13 Most Common Bariatric Procedures Sleeve Gastrectomy Roux-en-Y Gastric Bypass Biliopancreatic Diversion with Switch 260,000 procedures annually, 95% laparoscopic Madsbad S, Dirksen C, Holst JJ. Lancet Diabetes Endocrinol. 2014; 2: Sleeve Gastrectomy 38 Bariatric procedure originally as part of BPDDS, now used as a first stage or stand alone if patient loses enough weight Remove part of stomach, creating a sleeve from esophagus to antrum A 36Fr bougie is used to size the sleeve Now a covered benefit in US -- CMS Roux-en-Y gastric bypass (RYGB) Ghrelin GLP-1 PYY Insulin Excess Weight Loss is ~65-70%* 13

14 Duodenal Switch Combination Operation Sleeve Biliopancreatic Diversion Neurohormonal decreased Ghrelin and increased GLP1 Highest Remission rate for Type 2 Diabetes Excess Weight Loss is ~85% Significant risk of malabsorption of nutrients Usually performed on patients with a BMI>60kg/m2 STAMPEDE Trial Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently 218 Patients Screened A1c >7.0% BMI: kg/m 2 Age: years 150 Randomized 50 Intensive Medical Therapy Alone 8 withdrew consent 2 lost to follow-up 50 Medical Therapy + Gastric Bypass 2 lost to follow-up 50 Medical Therapy + Sleeve Gastrectomy 1 withdrew consent prior to surgery Year 3 Population % Retention Kashyap SR, et al. Diabetes Obes Metab. 2010;12:

15 STAMPEDE Trial: Change in A1c 0.0 Change in A1c (%) Sleeve Medical P <0.001 Gastric Bypass P < Value at Visit Baseline Month 6 Month 12 Month 24 Month 36 Medical 9.0 (8.5) 7.1 (6.8) 7.5 (6.9) 7.7 (7.3) 8.4 (7.6) Gastric Bypass 9.3 (9.2) 6.3 (6.2) 6.3 (6.1) 6.5 (6.4) 6.7 (6.6) Sleeve 9.5 (8.9) 6.7 (6.4) 6.6 (6.4) 6.8 (6.8) 7.0 (6.6) Kashyap SR, et al. Diabetes Obes Metab. 2010;12: STAMPEDE Trial: Change in BMI Change in BMI (kg/m 2 ) Medical Sleeve P <0.001 Gastric Bypass P < P=0.006 Value at Visit Baseline Month 6 Month 12 Month 24 Month 36 Medical Gastric Bypass Sleeve Kashyap SR, et al. Diabetes Obes Metab. 2010;12: Weight Change After Bypass and Sleeve vs Medical Tx In Patients with Type 2 DM Five-year data of patients with T2DM and BMI of 27 to 43 Medical Therapy Sleeve Gastrectomy -5.3 kg kg Gastric Bypass kg Mean BMI Value at Visit Schauer PR, et al. N Engl J Med Feb 16;376(7):

16 Five-year Outcomes for Bariatric Surgery vs. Intensive Medical Therapy for Diabetes Schauer PR, et al. N Engl J Med Feb 16;376(7): Routine Vitamin and Mineral Supplementation for RYGB Patients Supplement Multivitamin-mineral / Prenatal Calcium citrate w/ vitamin D Elemental iron Vitamin B12 Dosage 1 to 2 daily 1200 to 2000 mg/day U/day Vitamin D 40 to 65 mg/day 5000 ug/day orally OR 1000 ug/mo IM OR 500 ug weekly intranasal RYGB = Roux-en-Y gastric bypass. Bariatric Surgery Low Mortality 5.0% Mortality Rate (%) 4.0% 3.30% 3.0% 2.0% 1.0% 0.93% 0.52% 0.0% 0.13% Bariatric Surgery Lap Chole Hip Replacement CABG When performed at a Bariatric Surgery Center of Excellence 16

17 Reduction of Premature Death 89% Reduction in Risk of Death Over 5 Years MORTALITY 10.0% 9.0% 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% 0.68% Bariatric* 6.17% Controls * Includes perioperative (30 day) mortality of 0.4% P= Currently Available Treatments: Risks and Efficacy Lower risk Diets VLCD Pharma Lower efficacy Devices* Lap band Sleeve Roux en Y bypass BPD DS Higher efficacy Higher risk *Gastric sleeve and vagal stimulator under phase 3 study. SVLCD: very low calorie diet Jensen. MD, Ryan DH, et al. J Am Coll Cardiol. 2013;pii:S (13) Accessed May 12,