CURRENT STRATEGIES FOR TREATING OBESITY Robert B. Baron MD MS Professor of Medicine Associate Dean for GME and CME Founding Director, UCSF Weight Management Program Declaration of full disclosure: No conflict of interest UCSF Acknowledgments l Michelle Guy MD l Jonathan Carter MD 1
Prevalence of Obesity 2011-2012 Obesity prevalence: Adults 34.9% Youth 16.9% No change since 2003-2004 Ogden Cl, JAMA 2014 Obesity Disparities: Example: BMI >35 Women, 40-59: 19.1% White: 16.9%, Black: 30.4%, Asian 4.6%, Hispanic 25.5% Men, 40-59: 12.2% White: 12.8%, Black: 15.7%, Asian 0, Hispanic 8.7% Ogden, JAMA 2014 2
Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2013 WA CA OR NV ID UT MT WY CO ND SD NE KS MN WI IA IL MO IN MI KY OH PA WV VA NY VT ME NH MA RI CT NJ DE MD DC AZ NM OK AR TN SC NC AK TX LA MS AL GA FL HI GUAM PR 15% <20% 20% <25% 25% <30% 30% <35% 35% For a 40 yo woman, with normal BP, lipids, and FBS which BMI is associated with the lowest allcause mortality? 1. 18 2. 24 3. 28 4. 34 5. 38 3
CLASSIFICATION OF OVERWEIGHT AND OBESITY BY BMI Obesity Class BMI (kg/m 2 ) Underweight <18.5 Normal 18.5 24.9 Overweight 25.0 29.9 Obesity I 30.0 34.9 II 35.0 39.9 Extreme Obesity III >40 BMI AND MORTALITY: Overall Combined NHANES I, II, and III data set BMI 25-59 y 60-69 y 70 y <18.5 1.38 2.30 1.69 18.5-<25 1.00 1.00 1.00 25 to <30 0.83 0.95 0.91 30 to <35 1.20 1.13 1.03 35 1.83 1.63 1.17 Flegal, JAMA, 2005 4
MORTALITY AND OBESITY Meta-analysis of 97 studies of 2.8M people, 270,000 deaths BMI HR Below 25 (Normal) 1.0 25-30 (Overweight) 0.94 Above 30 (Obese) 1.18 *** 30-35 (Grade 1 Obesity) 0.95 Above 35 (Grade 2/3 Obesity) 1.29 Flegal, JAMA, 2013 For a 40 yo woman, with normal BP, lipids, and FBS which BMI is associated with the lowest allcause mortality? 1. 18 2. 24 3. 28 4. 34 5. 38 5
Epidemic of Inactivity 60% US adults don t exercise regularly 25% are sedentary EXERCISE FOR OBESITY Meta-analysis of 43 RCTs: 3476 participants Exercise plus diet vs diet alone -1.1 kg Increased intensity of exercise -1.5 kg Exercise without weight loss Reduced: BP, triglycerides, blood sugar Shaw, Cochrane, 2006 6
FITNESS AND MORTALITY Aerobics Center Longitudinal Study 25,714 men, 44 years old, 14 year observational study CV death (RR) normal overweight obese Fit 1.0 1.5 1.6 Not fit 3.1 4.5 5.0 Total death (RR) normal overweight obese Fit 1.0 1.1 1.1 Not fit 2.2 2.5 3.1 Wei, JAMA 1999 7
COMPARISON OF WEIGHT LOSS DIETS WITH DIFFERENT MACRONUTRIENTS RCT of 811 patients, 4 diets: fat/protein/carbs 20/15/65; 20/25/55; 40/15/45; 40/25/35 6 months: 6kg, 7% weight; at 2 years: completers lost 4kg; 15% lost 10% of weight Results similar for: 15% pro v. 25% pro 20% fat v. 40% fat 35% carbs v. 65% carbs Attendance highly correlated with weight loss; satiety, hunger, lipids, insulin all equal Sacks, NEJM, 2009 Heterogeneity of Response to Weight Loss Diets: Insulin Resistance Insulin sensitive: low carb and high carb both effective for weight loss Insulin resistant: low carb more effective 8
Very Low Calorie Diets (VLCD) vs Low Calorie Diets (LCD): Meta-analysis of 6 RCTs Trials with direct comparisons Short-term: mean 12.7 weeks Long-term: mean 1.9 years Weight loss (as % of initial weight): short-term long-term LCDs 9.7 5.0 VLCDs 16.1 6.3 (p) (0.001) (0.2) WEIGHT LOSS DIET BOTTOM LINE The type of diet does not really matter for weight loss. Sticking to the diet does matter Calories trump macronutrients But, select healthy, nutrient rich foods 9
40 yo woman, BMI 36. Much to your surprise (and satisfaction), she has lost 35 pounds. In order to maintain her new weight, her lifelong daily calorie intake should be: 1. 2000 kcals 2 1800 kcals 3 1600 kcals 4. 1400 kcals 5. 1200 kcals 10
SUCCESSFUL WEIGHT LOSS MAINTENANCE High levels of physical activity Women 2545 kcal/week, men 3293 kcal per week 1-hour moderate intensity per day Only 9% report no physical activity Diet low in calories 1381 kcal day 4.87 meals or snacks/day Fast food 0.74/week Regular self-monitoring of weight 44% weigh once per day; 31% once per week 40 yo woman, BMI 36. Much to your surprise, she has lost 35 pounds. In order to maintain her new weight, her lifelong daily calorie intake should be: 1. 2000 kcals 2 1800 kcals 3 1600 kcals 4. 1400 kcals 5. 1200 kcals 11
In the last year, I have prescribed a medication for weight loss. 1. Yes 2 No 12
The medication I have most commonly prescribed for weight loss is: 1. Phentermine 2. Orlistat (Xenical, Alli ) 3. Locaserin (Belviq ) 4. Phentermine/topiramate (Qsymia ) 5. Buproprion/naltrexone (Contrave ) 4. Liraglutide (Saxenda ) 5. Other The Neuroendocrinology of Energy Balance 13
Weight Loss With Weight Loss Medications Weight loss (% of initial) in excess of placebo: Phentermine-fenfuramine 11.0% Sibutramine 5.0% Phentermine 8.1% Orlistat 3.4% Lorcaserin (2012) 3.0% Phentermine/topiramate (2012) 7.8-9.3% Buproprion/naltrexone (2014) 2-4% Liraglutide (2014) 3.7-4.5% SIBUTRAMINE AND CARDIOVASCULAR OUTCOMES (SCOUT) 9804 patients, over 55, with CV disease or diabetes Sibutramine vs. placebo, 3.4 year f/u Outcomes MI, stroke, cardiac arrest, CV death Results Weight: -1.7 kg BP: 1.2 vs 1.4 mm Hg Combined outcome: 11.4% vs. 10.0% (HR 1.16, p = 0.02) Nonfatal MI: 4.1% vs. 3.1% (HR 1.28; p = 0.02) Nonfatal Stroke: 2.6% vs 1.9% (HR 1.36; p = 0.03) Death: No differences James, NEJM 2010 14
Phentermine/Topiramate (Qsymia ) Side Effects Paraesthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth Fetal harm: cleft lip, cleft palate Mood disorders: anxiety and depression Suicidal thoughts or behavior Acute angle glaucoma Cognitive dysfunction: concentration memory, language Metabolic acidosis and renal failure Hypoglycemia (in association with diabetes meds) Interactions with alcohol and sedatives PRINCIPLES OF DRUG THERAPY NIH: BMI > 30 kg/m 2 or 27 kg/m 2 with comorbidity (but in my practice almost never) Motivated to begin structured exercise and low calorie diet Begin medications at completion of one month successful diet and exercise Continue medications only if additional weight loss achieved in first month with meds 15
Wouldn t It Be Easier Just To Have Surgery? INDICATIONS FOR BARIATRIC SURGERY Definition BMI Normal < 25 Overweight 25-29.9 Obese, class 1 30-34.9 Obese, class 2 35-39.9 Obese, class 3 40+ Superobese 60+ with co-morbidity SURGERY 16
Restrictive Types of Surgery Horizontal Gastroplasties Vertical Banded Gastroplasty (VGB) Silastic Ring Vertical Gastroplasty (SRVG) Adjustable Gastric Banding Sleeve Gastrectomy Malabsorptive Jejunoileal Bypass (JIB) Biliopancreatic Diversion (BPD) Duodenal Switch Long Limb Gastric Bypass Restrictive with Malabsorptive Component Roux-en-Y Gastric Bypass (RYGPB) Surgical considerations Surgeon s Experience Restrictive vs Malabsorptive Open vs Closed 17
Lap Band Sleeve Gastrectomy Gastric Bypass Laparoscopic Adjustable Gastric Banding (LAGB) Restrictive Only Ideal Candidate BMI 35-40 kg/m2 Wants to lose 50-100 pounds Benefits Fewer early risks than other procedures One hour procedure Fully Reversible/Removable Lowest risk of vitamin deficiencies Considerations/Risks Excess Weight Loss (EWL) 50% 10-year removal or reoperation rate is >25% Slower weight loss (1-2lbs/week) compared to other surgeries Appetite suppression may be difficult to achieve Least effective for resolving diabetes 18
LONG-TERM OUTCOMES OF LAP BAND 151 patients, single center, 12 year f/u; 54.3% included (82/151) Operative mortality: 0 Mean weight loss: 20.75 kg (BMI from 41.6 to 33.8) 60% of patients satisfied; overall quality of life unchanged 39% major complications; 60% required re-operation Conclusion: Lap band results in poor long-term outcomes LABS Consortium, NEJM, 2009 Sleeve Gastrectomy (Ver=cal Gastrectomy) Restriction and Resection Ideal Candidate BMI 35-55 kg/m2 Wants to lose 80-150 lbs Benefits Excess Weight Loss 70-90% 1-2 hour procedure Recovery ranges from days to weeks Patients report early and lasting fullness Intestines stay intact No malabsorption May cure diabetes Considerations/ Risks Removal of a portion of the stomach is permanent The remaining pouch may expand over time 19
UCSF Sleeve Gastrectomy Indications Very high risk of co-morbidities BMI >60 Possible non-compliance with meds (less risk of micronutrient deficiencies) IBD, IBS, abdominal pain, SBO, adhesions, other GI morbidities Roux en Y Gastric Bypass (RNY or Bypass) Restrictive and Malabsorptive Most common procedure performed Ideal Candidate BMI 35-55 kg/m2 Wants to lose 100-150 + lbs May have severe or prolonged medical conditions Benefits Excess Weight Loss 70-90% 2 hour procedure Recovery of days to weeks Very effective for diabetes Approximately 100-200 calories per day lost through malabsorption Procedure is reversible Considerations/Risks Greater risk for vitamin deficiencies Dumping syndrome Smoking, EtOH, NSAIDS use may lead to ulcers 20
Duodenal Switch Restriction, Resection and Malabsortion Ideal Candidate BMI > 60 kg/m2 Poorly controlled diabetic Benefits Has the highest cure rate for diabetes Excess Weight Loss 80-90%. 3-4 hour procedure 200-400 cal lost from malabsorption Considerations/Risks Not offered by most surgeons Stomach removal is permanent but bypass may be reversed Highest risk for vitamin and protein deficiencies, diarrhea and intestinal blockages Contraindications to Bariatric Surgery Severe cardiac disease with high risk for anesthesia Severe coagulopathy Untreated major depression or psychosis Binge-eating disorders Current drug or alcohol abuse Inability to comply with post op diet and supplementations 21
Pre-op Evaluation Complete H and P Routine labs Nutrient screening ( Fe, Ferritin,TIBC, Vit D, Folate, Mg, Phos Cardio-pulmonary (sleep, ECG, CXR, Echo) GI (H pylori, GB, EGD) Endo (A1C, TSH, androgens, Cushings Psych social evaluation Diet evaluation Health Care Maintenance Bariatric Surgery: Weight Change Years 22
Resolution of Comorbidities Bariatric Surgery A Systematic Review and Meta-analysis Buchwald H. et al. JAMA. 2004; 292(14):1724-37 100 90 % Resolution Comorbidity 80 70 60 50 40 30 Band VBG GBP D Switch 20 10 0 Diabetes Hyperlipidemia HTN Sleep apnea ADA Practice Guidelines Bariatric Surgery for Diabetes l Bariatric Surgery may be considered for adults with BMI > 35 and type 2 DM, especially if diabetes and comorbidities are difficult to control with lifestyle and meds l Although small trials have shown glycemic benefit with BMI 30-35 and DM, there is currently insufficient evidence to recommend surgery ADA, Diabetes Care 2015 23
BARIATRIC SURGERY ADVERSE OUTCOMES Ten sites, 4776 patients. 3/4 roux-en-y (87% lap); 1/4 lap band 30 Day overall mortality: 0.3% -lap band 0.0% -roux-en-y (lap) 0.2% -roux-en-y (open) 2.1% Composite (death, DVT, reintervention, 30 + days in hosp): 4.1% -lap band 1.0% -roux-en-y (lap) 4.8% -roux-en-y (open) 7.8% LABS Consortium, NEJM, 2009 Mortality After Surgery Community Medicare Data: 55-64 year old 30 days 90 days 1 Year 2.0% 2.7% 5.2% 24
Post-operative Complications Gastric Banding Band Slippage Band Erosion Port infection Injury to adjacent organs Death within 30 days (<0.5% of patients) Sleeve Gastrectomy Leakage Bleeding Abdominal pain Poor wound healing Narrowing/ Stenosis Reflux Death within 30 days (<1% of patients) Bypass Surgery Leakage Bleeding Stoma obstruction Small bowel obstruction DVT Protein-calorie malnutrition Death within 30 days (<1% of patients) Additional Post-Operative Complications Mood Changes Excessive Vomiting Gas Dumping Syndrome Hair loss Eustachian Tube Dysfunction 25
Bariatric Surgery and Mortality Swedish Obese Subjects Study 4047 subjects, surgery vs. matched control. 10.9 years Max weight loss % Final weight loss % Control 2 Gastric bypass 32 25 Vertical banded Gastroplasty 25 16 Banding 20 14 Sjostrom, NEJM, 2007 Bariatric Surgery and Mortality Swedish Obese Subjects Study Deaths HR Rate MI deaths Cancer deaths Control 129 0.063 25 47 Surgery 101 0.76 0.050 13 29 (p = 0.04) NNT 77 over 11 years (approx 850 per year) Sjostrom, NEJM, 2007 26
Diet and Exercise After Surgery Days 1-14 Days 15-30 Day 31 and beyond Thin fluids only No solid food 32-60 oz fluids per day 400-600 calories per day 50-70 grams of protein Walk 5-10 minutes every hour Wake and walk after 8 hours Start thick liquids and soft foods 32-60 oz fluids 600 calories per day 50-70 grams of protein Minimal carbs and fats Start cardio exercises and light weight lifting Regular foods as tolerated Meats and other foods should be tender, cut and chewed well and eaten slowly 60+ oz fluids 600 calories per day 50-70 grams of protein Increase physical activity Keys to Success DO THIS Protein first, Goal 60+ g/day Eat 3 meals per day, Goal 600 cal/day Chew Chew Chew Drink water between meals Drink 64 oz fluids per day Measure and track all intake Exercise 30 to 60 minutes daily Weigh weekly Take your vitamins DON T DO THIS Eat sweets or excessive carbohydrates Overeat or graze Drink within 30 minutes of eating Drink carbonated beverages Drink through a straw Drink caffeine and alcohol Eat soft or high calorie foods Exceed calorie limits per day 27
Recommended Follow-Up Labs Basic labs CBC Electrolytes BUN and creatinine Liver panel Lipid panel Glucose and A1C Deficiencies Folate Iron, ferritin, and TIBC B-12 Calcium Vitamin D Also consider Magnesium Phosphorus B6 Thiamine (B1) Zinc Copper Vitamin A 55 Medication Issues After Surgery Diuretics are discontinued in the hospital Attempt to use immediate-release, crushed, liquid or chewable preparations Patient are often discharged from the hospital off HTN and DM meds If meds are needed in diabetics use immediate release Metformin and/or sliding scale insulin Avoid delayed, enteric-coated and extended-release preparations after malabsorption procedures Some meds require gastric acidity for dissolution Avoid NSAIDS, EtOH and smoking cessation to prevent ulcers 28
Pregnancy and Weight-Loss Surgery Fertility is enhanced after surgery Delay pregnancy for 12 to 18 months after surgery Use non-oral forms of birth control Avoid oral glucose challenge after gastric bypass Managing Excess Skin 29
SUMMARY l Environmental and public health changes work. l Diets work, but not for long in most people (but they do for some). l Exercise improves health independent of weight change and aid in weight maintenance. l Continuation of conditions that promote weight loss promotes weight maintenance (no matter what the intervention). SUMMARY l Provision of meals and meal replacement products promote greater weight loss (but mostly in the short term, except for a few). l Medications can help achieve small amounts weight loss for as long as agents can be used (but little is known about long term outcomes). l Surgery results in long term weight loss and reductions of diabetes and mortality (but with complications in some/many and a high number needed to treat). 30
GOALS OF MANAGEMENT l Be as fit as possible at current weight l Prevent further weight gain l If successful at 1 and 2, begin weight loss The Magic Formula 31