1 / 44

Comprehensive Approaches to Intervention for Weight Loss

This article explores various strategies for weight loss, including lifestyle changes, diet, exercise, and pharmacotherapy. It discusses the benefits of weight loss and its impact on diabetes, cholelithiasis, hypertension, and coronary heart disease.

knutter
Download Presentation

Comprehensive Approaches to Intervention for Weight Loss

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Comprehensive Approaches to Intervention George A. Bray, MD, MACE Pennington Biomedical Research Center Louisiana State University Baton Rouge, Louisiana

  2. Key Points • Weight loss is beneficial • Several strategies will produce weight loss • Lifestyle changes • Diet • Exercise • Pharmacotherapy • Summary

  3. BMI Has Biggest Effect on Diabetes Men Women 6 6 5 5 Relative Risk Relative Risk 4 4 3 3 2 2 1 1 22 23 29 30 <21 24 25 26 27 28 <21 22 23 29 30 24 25 26 27 28 0 0 BMI (kg/m2) BMI (kg/m2) Type 2 diabetes Cholelithiasis Hypertension Coronary heart disease BMI, body mass index. Willett WC et al. N Engl J Med. 1999;341(6):427–434.

  4. Small Weight Loss Reduces Risk of Diabetes in the DPP Placebo Reduces Risk of Diabetes by 58% Lifestyle Weight Change in DPP (kg) 0 6 12 18 24 30 36 42 48 Months in Study DPP, Diabetes Prevention Program. Knowler WC et al. N Engl J Med. 2002;346(6):393–403.

  5. How Much Weight Loss Is Needed to Prevent Type 2 Diabetes? 20 15 Incidence Rate per 100 Person-Years 10 5 0 -10 -5 0 +5 Change in Weight From Baseline (kg) Redrawn from: HammanRF et al. Diabetes Care. 2006;29(9):2102–2107.

  6. Key Points • Weight loss is beneficial • Several strategies will produce weight loss • Lifestyle changes • Diet • Exercise • Pharmacotherapy • Summary

  7. Components of Behavior Therapy for Obesity Problem solving Self-monitoring Cognitive restructuring Contingency management Obesity Social support Stimulus control Stress management Wadden TA, Foster GD. Med Clin North Am. 2000:84(2):441–461.

  8. 4-Year Weight Loss in the Look AHEAD Trial Weight Change From Baseline (%) DSE ILI Year Repeated measures adjusted for clinic and baseline level. P value for average effect across all visits: P < 0.0001. DSE, diabetes support and education; ILI , intensive lifestyle intervention. Look AHEAD Research Group, Wing RR. Arch Intern Med. 2010;170(17):1566–1575.

  9. Lifestyle Intervention Was Clinically Effective in All Subsets of an Ethnically and Demographically Diverse Population Non-Hispanic White Other/Mixed African American Hispanic 0.0 2.0 Male Female 4.0 Reduction (%) in Initial Weightin ILI Participants 6.0 8.0 10.0 12.0 Wadden TA et al. Obesity (Silver Spring). 2009;17(4):713–722.

  10. Correlates of Weight Loss: Look AHEAD Rank Order of Importance • Self-reported physical activity • Diet and physical activity counseling sessions attended • Consumption of meal replacements • At 1 year, ILI participants lost more weight if: • Attended more treatment sessions • Exercised more • Consumed more meal replacement products

  11. Key Points • Weight loss is beneficial • Several strategies will produce weight loss • Lifestyle changes • Diet • Exercise • Pharmacotherapy • Summary

  12. ARS: Which intervention was most effective in reducing the risk of diabetes among those at risk in the DPP? ? • Diet and exercise • Metformin

  13. DPP Results: 3.2-Year Progressionfrom IGT to T2DM 58% reduction IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.Knowler WC et al. N Engl J Med. 2002;346(6):393–403.

  14. ARS: A reduced-calorie diet emphasizing which of the following is associated with the greatest weight loss? ? Carbohydrate Fat Protein No difference

  15. POUNDS LOST: Weight Loss (ITT) Diet Composition Carbohydrate/Protein/Fat 0 –1 65/15/20 55/25/20 45/15/40 35/25/40 –2 –3 Weight Loss (kg) –4 –5 –6 –7 0 6 12 18 24 Months ITT, intent to treat.Sacks FM et al. N Engl J Med. 2009;360(9):859–873.

  16. POUNDS LOST: Weight Change and Attendance: High Protein, High Fat 30 20 10 0 –10 Weight Change (kg) –20 –30 –40 –50 0 10 20 30 40 50 60 N = 168 Slope = –0.217 P < 0.001 Number of Sessions Attended Sacks FM et al. N Engl J Med. 2008;360(9):859–873.

  17. Dietary Components That Predict 4-Year Changes in Body Weight Weight effects, lb Whole grains Vegetables Fruits Nuts Yogurt Fried foods home Trans fat Processed meats Red meats Sugared beverage Potato fries Potato chips Mozafferian D et al. N Engl J Med. 2011;364(25):2392–2404.

  18. Key Points • Weight loss is beneficial • Several strategies will produce weight loss • Lifestyle changes • Diet • Exercise • Pharmacotherapy • Summary

  19. Non-Exercise Exercise 8 18 Treatment (weeks) Follow-up (months) Effect of Exercise on Initial Rate of Weight Loss and on Subsequent Weight Status Pavlou KN et al. Am J Clin Nutr. 1989;49(5 suppl):1110–1114.

  20. High Activity Needed for Weight Loss Maintenance P Values Group effect <0.001 Time effect <0.001 Group X time effect <0.02 0 –2 –4 –6 Percent Weight Loss (%) –8 –10 –12 –14 Change in Weight (kg) –16 0 6 12 18 24 Months <150 min/wk (N = 86) 150–249 min/wk (N = 19) 250–299 min/wk (N = 21) ≥300 min/wk (N = 44) *P<0.05. Jakicic JM et al. Arch Intern Med. 2008;168(14):1550–1560.

  21. Key Points • Weight loss is beneficial • Several strategies will produce weight loss • Lifestyle changes • Diet • Exercise • Pharmacotherapy • Summary

  22. Pharmacotherapy • For obesity without comorbidities • For obesity with diabetes mellitus • Drugs in limbo

  23. Drugs Approved by the FDA for Treatment of Obesity FDA, Food and Drug Administration; DEA, Drug Enforcement Administration. • Sympathomimetics • Diethylpropion (DEA Schedule IV) • Phentermine (DEA Schedule IV) • Benzphetamine (DEA Schedule III) • Phendimetrazine (DEA Schedule III) • Orlistat

  24. Effect of Long-term Treatment With Orlistat (The XENDOS Study) 0 –3 Placebo + Lifestyle P<0.001 –6 Change in Body Weight (kg) Orlistat + Lifestyle –9 –12 0 52 104 156 208 Weeks of Treatment Torgerson JS et al. Diabetes Care. 2004;27(1):155–161.

  25. Pharmacotherapy • For obesity without comorbidities • For obesity with diabetes mellitus • Drugs in limbo

  26. ARS: Which of the following classes of drugs for patients with diabetes is associated with weight loss? ? DPP-4 inhibitors GLP-1 agonists Insulin Sulfonylureas Thiazolidinediones DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1.

  27. Slide Unavailable Bray, Circulation in press

  28. DPP: Metformin and Lifestyle Over Time 2 0 –2 Change in Weight (kg) –4 Placebo Metformin Lifestyle –6 –8 0 1 2 3 4 5 6 7 8 9 10 Year Since DPP Randomization DPP Research Group. Lancet. 2009;374(9702):1677–1686.

  29. Pramlintide Produced Weight Loss: % Change in Weight (ITT Populations, Observed Data) Placebo 120 µg Pramlintide 240 µg Pramlintide 360 µg Pramlintide BID Regimen TID Regimen Evaluable ITT-LOCF Evaluable ITT-LOCF 1 1 Double-blind study Single-blind extension Double-blind study Single-blind extension 0 0 -1 -1 -2 -2 -3 -3 -4 -4 Mean (±SE) Change in Body Weight (kg) -5 -5 Mean (±SE) Change in Body Weight (kg) * -6 -6 * ** * * ** ** * -7 -7 * ** -8 -8 ** -9 -9 -10 -10 -11 -11 0 4 8 12 12 0 4 8 12 12 Time (mo) Time (mo) Number of Subjects Placebo 36 120 µg BID 38 240 µg BID 32 360 µg BID 39 Number of Subjects Placebo 36 120 µg BID 38 240 µg BID 45 360 µg BID 42 36 17 38 24 32 17 39 21 17 25 16 21 17 24 17 21 27 28 25 32 36 17 38 25 45 23 42 18 17 25 23 18 17 25 23 17 27 29 30 38 *P < 0.05 and **P < 0.01 for each pramlintide treatment group versus placebo. Smith SR et al. Diabetes Care. 2008;31(9):1816–1823.

  30. Combination of Pramlintide and Phentermine on Body Weight 0 Placebo Pramlintide –5 Weight Loss (kg) –10 Pram + Phen –15 0 10 20 30 Weeks of Treatment Aronne L et al. Obesity (Silver Spring). 2010;18(9):1739–1746.

  31. Exenatide:* An Anti-diabetic Drug That Produces Weight Loss 0.5 0 -0.3 ± 0.3 kg -0.5 ** -1.0 ** -1.5 -1.6 ± 0.4 kg † Change in body weight (kg) ** -2.0 -2.5 † Placebo -2.8 ± 0.5 kg † -3.0 5 g Exenatide † 10 g Exenatide -3.5 † -4.0 0 5 10 15 20 25 30 Weeks *Not approved for treatment of obesity **P≤.05 vs placebo; †P≤.001 vs placebo. Defronzo RA, et al. Diabetes Care. 2005;28:1092-1100.

  32. Liraglutide,* an Antidiabetic Drug, and Orlistat Produce Weight Loss 0 Placebo 1.2 mg/day 1.8 mg/day 2.4 mg/day 3.0 mg/day Orlistat –2 –4 Weight Loss (kg) Screening Randomization –6 –8 –10 –5 0 5 10 15 20 Weeks From Randomization *Not approved for treatment of obesity. Astrup A et al. Lancet. 2009;374(9701):1606–1616.

  33. Pharmacotherapy • For obesity without comorbidities • For obesity with diabetes mellitus • Drugs in limbo • Topiramate/phentermine • Bupropion/naltrexone • Lorcaserin

  34. Topiramate/Phentermine* Produces Weight Loss (Completers) 0 -2 -4 Placebo Phentermine 7.5 mg plus topiramate 46.0 mg Phentermine 15.0 mg plus topiramate 92.0 mg * * -6 * Weight change (kg) * -8 * * * * * -10 * * * -12 * * -14 0 8 16 24 32 40 48 56 Weeks of Treatment Study completers Placebo Phentermine 7.5 mg plus topiramate 46.0 mg Phentermine 15.0 mg plus topiramate 92.0 mg 979 488 981 851 437 843 744 403 775 670 387 747 623 369 712 589 356 686 573 350 660 557 338 625 *Investigational Gadde KM et al. Lancet. 2011;377(9774):1341–1352.

  35. Naltrexone-Bupropion* Produces Weight Loss (Completers) 0 Placebo N = 507 –2 –4 Weight Change from Baseline (kg) –6 NB 16 mg (N = 467) –8 NB 32 mg (N = 467) –10 Bupropion 360 mg/day Dropouts ̴ 50% 0 8 16 24 32 40 48 56 Weeks of Treatment *Investigational Greenway FL et al. Lancet.2010;376(9741):595–605.

  36. Lorcaserin* Produces Weight Loss (Completers) 0 –2 Placebo Crossover –4 Continuous Weight Loss (kg) –6 –8 –10 –12 0 8 16 24 32 40 48 56 64 72 80 88 96 104 Weeks of Treatment *Investigational Placebo N = 684 Crossover N = 275 Continuous N = 564 Smith SR et al. N Engl J Med. 2010; 363(3):245–256.

  37. Key Points • Weight loss is beneficial • Several strategies will produce weight loss • Lifestyle changes • Diet • Exercise • Pharmacotherapy • Summary

  38. Summary and Recapitulation • Weight loss is beneficial, particularly if disease risk is present • Several strategies will produce weight loss • Lifestyle changes/diet/exercise • Pharmacotherapy • Surgery • Summary

  39. 2010 Was A Momentous & Disappointing Year for Obesity With 5 FDA Panels July 15, 2010 – Combination of topiramate/ phentermine reviewed by FDA - 10 for 6 against Sept 15, 2010 – Continued marketing of sibutramine in light of SCOUT study was reviewed by FDA panel - 8 for and 8 against continued marketing Sept 16, 2010 – Lorcaserin new drug application reviewed by FDA Panel – 9 for and 5 against Oct 8, 2010 – Sibutramine withdrawn Dec 7, 2011 – BMI lowered for some surgical operations Dec 15, 2010 – Combination of buproprion/ naltrexone recommended 13/7 for approval. FDA is requiring an outcomes trial before approval

  40. Unintended Consequences of Drug Treatment for Obesity in the 20th Century Bray GA Battle of the Bulge, Dorrance Publishing 2007 p. 59

  41. Lesson for Today Osler W. Science 1891;17:170-171 • “A desire to take medicine is, perhaps, the great feature which distinguishes man from other animals”

More Related