How to Achieve Medical Weight Loss in 2012 Gary D. Foster, Ph.D. Laure H. Carnell Professor of Medicine, Public Health, and Psychology Director, Center for Obesity Research and Education Temple University Overview Rationale and Barriers Behavioral Treatment Dietary Treatment Pharmacological Treatment Patient Expectations
Rationale For Treating Obesity Many OSA patients are obese Reductions in weight are associated with improvements in SDB Reductions in weight improve many comorbidty conditions that obesity and OSA share Barriers Fatigue One more thing to do Multiple behavior changes
Obesity Treatment Guidelines The Practical Guide can be found at: NHLBI web site: www.nhlbi.nih.gov The Obesity Society web site: www.obesity.org Guide for Selecting Obesity Treatment BMI Category (kg/m 2 ) Treatment 25-26.9 27-29.9 30-34.9 35-39.9 >40 Diet, Exercise, Behavior Tx Pharmacotherapy Surgery + + + + + With comorbidities + + + With comorbidities + The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub. No.00-4084
Antecedent Behavior Consequence A Sample Behavior Chain Buy Cookies Leave Cookies on Counter Home on Saturday Afternoon Tired and Bored Eat While Watching TV Take Cookies to TV Room Go to Kitchen Urge to Eat Eat Rapidly Until Full Feel Guilty/ Like a Failure Restraint Weakens Further More Eating Brownell KD. The LEARN Program for Weight Control. 7th ed. American Health Publishing Co; 2003.
Self-Monitoring Food Intake Types of foods Portion sizes Calories (reduce by 500 kcal/d) Times, places, and activities Thoughts and moods Brownell: Learn Program for Weight Control, 1998
The Dieter s Dilemma Weight Loss with a Low-Carbohydrate, Mediterranean, or Low Fat Diet Sample description N=322 277 Male, 45 Female Age 52+7 BMI 30.9+3.6 Randomly assigned to 1 of 3 conditions Low-fat, restricted calorie Mediterranean, restricted calorie Low-carbohydrate, non-restricted calorie Shai et al. NEJM, 2008
Low-fat, restricted calorie (n=104) 1500 kcal/day for women; 1800 kcal/day men Diet based on American Heart Association guidelines 30% of calories from fats, 10% calories from saturated fats, 300 mg of cholesterol/day Mediterranean, restricted calorie (n=109) 1500 kcal/day for women; 1800 kcal/day men Diet rich in vegetables, low in red meat (replaced with fish or poultry) >35% of calories from fat Main source of added fats were 30 to 45 g of olive oil and a handful of nuts Low-carbohydrate, non restricted calorie (n=109) 20g of carbohydrates/day for induction phase with a gradual increase to a max of 120 g/day Diet based on the Atkins diet Diet Plans Shai et al. NEJM, 2008 Weight Changes during 2 Years According to Diet Group Shai et al. NEJM, 2008
Comparison of Low-Carbohydrate and Low-Fat Diets for Obesity: A Two-Year, Multi-Center Randomized Trial 317 Participants (208 women, 99 men) 45.5 ± 9.7 years old 36.1 ± 3.5kg/m 2 BMI 74.9% European American Participants were randomly assigned to either: Low-carbohydrate diet: Limited carbohydrate intake with unrestricted consumption of fat and protein. Low-fat diet: Limiting energy intake to 1200 to 1500 kcal/d for women and 1500 to 1800 kcal/d for men, with approximately 55 percent of calories from carbohydrate, 30 percent from fat, and 15 percent from protein. All participants received group behavior treatment for 2 years. Foster et al. Ann Intern Med, 2010 Weight Loss 0 Change in Weight (kg) -2-4 -6-8 -10-12 -14 Low-fat Low-carbohydrate 3 6 12 24 Month Foster et al. Ann Intern Med, 2010
Lipid Changes * * * * * Foster et al. Ann Intern Med, 2010 Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates Sample description (N=811) 515 female, 296 male Age 51.9 ± 9 years old BMI 33 ± 4.0kg/m 2 Weight 93 ±16 kg All participants were offered group and individual instructional sessions for 2 years. Sacks et al. NEJM, 2008
POUNDS LOST: Diets Diet Protein Fat Carbohydrate Orange 25% 40% 35% Green 15% 40% 45% Pink 25% 20% 55% Blue 15% 20% 65% Sacks et al. NEJM, 2008 POUNDS LOST: Body weight Over 2 Yrs, ITT 0-1 -2-3 -4-5 Diet Composition Carbohydrate/Protein/Fa t (% energy) 65/15/20 55/25/20 45/15/40 35/25/40-6 -7 0 6 12 18 24 Months Sacks et al. NEJM, 2008
Portion-Controlled Meals Provide fixed-portion and calorie amounts Reduce choices and contact with problem foods Are convenient to use Satisfy appetite (monotony and sensory specific satiety) Facilitate dietary adherence Meal Replacements Enhance Initial and Long-term Weight Loss Percentage Weight Loss 0 5 10 15 Phase 1* CF MR-2 Phase 2 MR-1 0 2 4 6 8 10 12 18 24 30 36 45 51 *1200 1500 kcal/d diet prescription. Time (mo) CF=conventional foods. MR-2=replacements for 2 meals, 2 snacks daily. MR-1=replacements for 1 meal, 1 snack daily. Ditschuneit et al.,am J Clin Nutr, 1999 Fletcher-Mors et al., Obes Res, 2000
Meta-Analysis of Partial Meal Replacements (PMR) vs. Reduced Calorie Diets (RCD) Mean Weight Losses for Completers Weight Loss (in kg) 4 2 0-2 -4-6 -8-10 *p<.001 *p<.001-4 -4.4-6.5-7 3 months 12 months RCD PMR Heymsfeld et al. IJO, 2003
Antiobesity Agents: How They Work Agents Releasing Agent Reuptake Inhibitor Selective Lipase Inhibitor 5-HT NE DA 5-HT NE DA Dexamphetamine +++ +++ Phentermine Sibutramine +++ +++ +++ +++ + Orlistat +++ 5-HT = serotonin; NE = noradrenaline; DA = dopamine 1 Bray, Ann Intern Med., 1993., 2 Beales, Kopelman PharmacoEconomics. 1994., 3 Buckett et al. Prog Neuropsychopharmacol Biol Psychiatry. 1988., 4 Drent et al. In J Obes Relat Metab Disord., 1995., 5 Heal et al. Psychopharmacology (Berl), 1992. Drugs Approved by FDA for Treating Obesity Status Generic Name Trade Name Rx Orlistat Xenical OTC (Approved 2/07) Orlistat60mg alli Rx (Withdrawn) Sibutramine Meridia Not approved in U.S. (Withdrawn in Europe) Rimonabant Acomplia/Zimulti
Orlistat: Weight Loss and Maintenance Over 2 Years Change in Body Weight (%) 0 1 2 3 4 5 6 7 8 9 10 11 12 Placebo Orlistat P<0.001 vs placebo at 1 and 2 years 10 0 10 20 30 40 50 60 70 80 90 100 110 Week SB DB DB SB = single blind; DB = double blind Slightly hypocaloric diet Weight maintenance (eucaloric) diet Adapted with permission from Sjöström L et al. Lancet, 1998
Orlistat: Safety Adverse Events (AEs) at 1 Year 40 30 31% Placebo, n=340 Orlistat, n=343 % 20 20% 18% 10 0 5% Fatty/Oily Stool 7% Increased Defecation 1% Oily Spotting There is concern about fat-soluble vitamin absorption 3% 10% Fecal Urgency 0% 7% Fecal Incontinence Sjöström L et al. Lancet, 1998 Treatment Guidelines Orlistat Prescribe 120 mg tid, with meals containing fat Patients should be on a nutritionally balanced, reduced-calorie diet Diet should contain approximately 30% of calories from fat Distribute fat among three meals a day Use a multivitamin daily Encourage patients to enroll in XeniCare, the orlistat patient support group
alli vs. Xenical alli Xenical Use OTC Rx Dosage 60 mg 120 mg Target Pop Overweight BMI > 27kg/m 2 or > 30 kg/m 2 (w/co-morbidities) or (without) Indication Weight loss Weight loss & Maintenance Age Range 18+ 12+ GI AEs (withdrawal rates) Behavioral Support Program 3.2 5.4 Myalliplan.com Xenicare Drug development timelines 1997 sibutramine 1999 orlistat OTC Orlistat Lorcaserin Phen/ Topiramate Bupropion + Naltrexone Bupropion + Zonisamide GLP-1 analogs Leptin + Pramlintide Rimonabant Taranabant Obipinabant
Defined Weights Dream Weight A weight you would choose if you could weigh whatever you wanted. Happy Weight This weight is not as ideal as the first one. It is a weight, however, that you would be happy to achieve. Acceptable Weight A weight that you would not be particularly happy with, but one that you could accept, since it is less than your current weight. Disappointed Weight A weight that is less than your current weight, but one that you could not view as successful in any way. You would be disappointed if this were your final weight after the program. Foster et al, J Consult Clin Psychol, 1997 Defined Weights % Reduction 1 % Reduction 2 Dream 38% 38.4% Happy 31% 30.9% Acceptable 25% 24.9% Disappointed 17% 15.7% 1 Foster et al. JCCP 65(1) 79-85 1997 2 Foster et al Arch Int Med. 161 2133-2139 2001
% Achieving Defined Weights at Week 48 (N=45, Weight loss: 16.3 + 7.2 kg) Acceptable 24% 9% Happy Dream = 0% 20% Disappointed 47% Did not reach Disappointed Weight Foster et al, J Consult Clin Psychol, 1997
Helping Patients Accept More Modest Weight Losses Be clear about what treatment can do and what it cannot do Discuss biological limits Focus on nonweight outcomes Be empathic about dissatisfaction with weight/shape