Long term Weight Management in Obese Diabetic Patients Osama Hamdy, MD, PhD, FACE

Long term Weight Management in Obese Diabetic Patients Osama Hamdy, MD, PhD, FACE Medical Director, Obesity Clinical Program, Director of Inpatient Diabetes Management, Joslin Diabetes Center Assistant Professor of Medicine Harvard Medical School Boston, Massachusetts, USA

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Obesity and Diabetes: the Twin Epidemics Rates of diabetes and obesity are dramatically high worldwide, with an average of 17% of people suffering from obesity 7% of people with diabetes Obesity prevalence rates (2009) Diabetes prevalence rates (2010) % % OECD (2011), Overweight and obesity among adults, in Health at a Glance 2011: OECD Indicators, OECD Publishing. http://dx.doi.org/10.1787/health_glance-2011-18-en OECD (2011), Diabetes prevalence and incidence, in Health at a Glance 2011: OECD Indicators, OECD Publishing. http://dx.doi.org/10.1787/health_glance-2011-13-en 3

90.0 Number of US Individuals with Obesity 80.0 Number in Millions 70.0 60.0 50.0 40.0 30.0 20.0 40.6 37.5 Women Men 10.0 7 0.0 5.5 Age >20 ys Age 2-19 4 CDC/NCHS, National Health and Nutrition Examination Survey, 2009 2010

Objectives 1 Can long term weight loss be achieved? 2 What are the keys for long term maintenance of weight loss? 3 Is non surgical weight reduction cost effective? 5

Type of Intervention Short term Weight Loss (< 1 year) Advice to change lifestyle.. +/ 5 lbs (2%) Lifestyle intervention program 5 10 lbs (2 5%) Intensive lifestyle intervention program 10 20 lbs (5 7%) Optimal intensive lifestyle intervention program 20 30 lbs (10 15%) Long term Weight Loss (4 8 years) Intensive lifestyle intervention program 4.7% Optimal intensive lifestyle intervention program 6.3% 6

Weight Losses in ILI were Significantly Greater Than in DSE and Sustained Over a 4 year Period (Look AHEAD Study) Time (years) Weight change from baseline (%) *P <0.001 * * * * 7 Look Ahead Research Group. Arch Intern Med. 2010;170(17):1566 1575.

Weight Loss Through Year 8 (Look AHEAD study) Percent Reduction in Initial Weight 0-2 -4-6 -8 DSE P<.001 for comparisons at all years -10 0 1 2 3 4 5 6 7 8 ILI -2.1% -4.7% Years 8 Adapted with permission from Wadden TA, et al. Obesity. 2011;19:1987.

Four Year Weight Loss Trajectories of 887 ILI Participants Who Had Lost 10% Initial Weight at Year 1 Percentage Weight Loss +4 +2 0 2 4 6 8 10 12 14 16 18 Gained 0-5% 5-6.9% 7-10% 10% Wadden TA et al. Obesity 2011;19:1987 1 2 3 4 Years N=88 (9.9%) N=174 (19.6%) N=99 (11.2%) N=152 (17.1%) N=374 (42.2%) 9

0 Long term Reduction in Body Weight after Optimal Lifestyle Intervention in Clinical Practice -5 Weight Loss in Pounds -10-15 -20-15.6 (-6.3%) -25-30 0 12 W 3 M 6 M 9 M 12 M 15 M 18 M 21 M 24 M 27 M 30 M 33 M 36 M 39 M 42 M 45 M 48 M Total 0-24.2-23.9-23.5-19.9-17.9-17.3-15.95-14.3-14.99-13.6-14.65-14.4-14.5-14.4-14.85-14.7-15.6 N= 120 10 Hamdy O. et al. ADA, Philadelphia, 2012

0-5 Long term Reduction in Body Weight after Optimal Lifestyle Intervention in Clinical Practice Weight Regain (52% of Participants) -8.0 (-3.3%) Weight Loss in Pounds -10-15 -20-25 -30-35 -40 * * ** ** *** ********* 0 12 W 3 M 6 M 9 M 12 M 15 M 18 M 21 M 24 M 27 M 30 M 33 M 36 M 39 M 42 M 45 M 48 M Group A 0-29.2-31.98-34.3-32.8-31.5-29.4-27.1-26.6-23.9-22.8-23.98-22.4-23.5-23.8-24.6-23.8-24.1 Group B 0-19.6-16.66-13.88-8.2-5.59-6.4-5.9-3.3-6.9-5.3-6.2-7.3-6.3-5.9-5.99-6.4-8 Total 0-24.2-23.9-23.5-19.9-17.9-17.3-15.95-14.3-14.99-13.6-14.65-14.4-14.5-14.4-14.85-14.7-15.6 ** Total Group -15.6 (-6.3%) Weight Maintenance (48% of Participants) * ** * ** ** ** -24.1 (-9.5%) N= 120 (Group A 57, Group B 63) A versus B * p<0.05, ** P<0.01, *** P<0.001 Hamdy O. et al. ADA, Philadelphia, 2012 11

Distribution of Levels of Weight Maintenance at 1 Year and 2 Year Follow up Assessments by Method of Initial Weight Loss Lost >5.0 Kg Maintain +4.9 Kg Gain >5 Kg Lost >5.0 Kg Maintain +4.9 Kg Gain >5 Kg Year 1 Year 2 NWCR registry: Weight loss >13.6 and maintaining 13.6 kg for a year Average weight loss 56 kg and maintenance of >13.6 kg for 5.5 years Bond DS et al. Int J Obes. 2009 Jan;33(1):173-80. 12

Keys to Optimal Lifestyle Intervention for Long term Weight Reduction 1. Aim for meaningful weight loss goal (5 10%) 2. Gradual and balanced and individualized physical activity 1. Duration of exercise 2. Type of exercise 3. Exercise records 3. Structured dietary intervention & modified macronutrient composition 1. Relatively higher protein, LGI & higher fibers 2. Provided menus 3. Food records 4. Diabetes specific meal replacement (GTSN) 4. Medication adjustment and frequent BG monitoring 5. Counseling and cognitive behavioral change 6. Group intervention and frequent participant contact 7. Daily weighing 13

1 Aim for Modest Weight Loss through Defining a SMART Goal Effect of weight loss on insulin sensitivity * Change From Baseline (%) * * * Weight BMI W/H Insulin Sensitivity BMI = body mass index; W/H = waist-to-hip-ratio. *P<0.001 Hamdy O, et al. Diabetes Care. 2003;26:2119-2125 14

2 Gradual, balanced and individualized physical activity Duration of exercise Type of exercise Short versus long bouts of exercise Exercise records/exercise monitor Visceral Fat The benefits of Exercise and or Increased Physical Activity include BP & lipids Metabolic Control Physical Fitness & QOL Maintenance of Weight Loss Vascular Resistance 15

Diabetes, a Common Comorbidity, Significantly Accelerates Loss of Muscle Mass, Strength and Quality Loss of Muscle Mass (gm/year) * * Loss of Total Muscle Mass [g/ year] p<0.05* Park SW, et al. Diabetes Care 2009;32:1993-1997. 16

Exercise Preserves Muscle Mass During Weight Reduction *P<0.05 Loss of Muscle Mass (As % of Total Weight Loss) Men Women Diet Diet + Exercise 17 Ballor DL and Poehlman ET. Int J Obes Relat Metab Disord. 1994;18(1):35-40.

Balanced Exercise Model Flexibility Aerobic Strength Stretching Yoga Walking Swimming Biking Dancing Resistance tubing Weight lifting Yoga Strength exercise is particularly important during weight reduction 18

Gradual and balanced exercise intervention* Independent Exercise Progression Week Frequency of Exercise* Duration of Exercise Type of Exercise 1 4 4 days /wk 20 40 min AEX + STCH + CST + CT 5 8 5 days /wk 40 45 min AEX + CT+ IT + STCH + Y + CSE 9 12 6 days /wk 50 60 min IT + CT + CSE +SS + Y + STCH AEX Aerobic Exercise SS Superset Training IT Interval Training CSE Core Stability Exercise CT Circuit Training STCH Stretching Exercise CST Cross Training Y Yoga (Vinyasa flow) * Model used in the Why WAIT program 19 Shahar J et al, ADA 2009

Changes in % Body Fat, Fat Mass & Lean/Fat Ratio after 12 Weeks of Balanced Exercise Plan Fat Mass (lbs) Body Fat (%) Lean/Fat Ratio * Body Fat Mass in lbs *** *** n = 85 * p <0.05 ** p <0.01 *** p <0.001 Hamdy O et al Obesity Management J. 2008; 4(4):176-183 20

Percent Weight Loss for Categories of 24 month Physical Activity (N = 170) 21 Jakicic JM et alarch Intern Med. 2008; 168(14): 1550 1560

Effect of Long vs. Short Bouts of Exercise on Adherence and Weight Loss 10 Activity (min/week) 8 6 4 2 Weight Loss (kg) Long Bouts Short Bouts Long Bouts Short Bouts 0 Long bout = one 40-min session. Short bout = four 10-min sessions. 22 Jakicic et al. J Obes Relat Metab Disord 1995;19:893.

3 Structured dietary intervention & modified macronutrient composition Relatively higher protein, LGI & higher fibers Provide structure menus Calorie replacements Food records Calorie intake Carbs to 40-45% Natural food (dinner menus and snacks) and Calorie Replacement Glycemic index Protein intake to 30% Fiber MUFA Saturated fat and sodium 23

Diets with High or Low Protein Content and Glycemic Index for Weight Loss Maintenance (26 weeks) n= 773 Initial weight loss >8% Larsen TM et al. N Engl J Med 2010;363:2102-13. 13% protein (LGI/HGI) versus 25% protein (LGI/HGI) 24

The Metabolic Effect of Different Protein/Carbohydrates Ratios in Type 2 DM Protein to carbohydrate to fat: 30:40:30 Versus 15:55:30-0.3% -0.8% Total glycated hemoglobin response of subjects to the control (15% protein) and high-protein (30% protein) diets over the 5-wk study period. *Significantly different from the control diet, P < 0.05 The rate of decline was also significantly greater after the high-protein diet, P < 0.001 Adapted from Gannon MC et al. Amer J Clin Nutr 2003;78:734-741 25

Strong Correlation Between Calorie Replacement and Weight Loss (Look AHEAD Study) Number in the bar is mean number of MRs used in that quartile Reduction in Initial Weight in ill participants (%) MRs 117 277 406 608 MRs = meal replacements. Reproduced with permission from Wadden TA et al. Obesitiy 2009; 17:713-722 26

4 Adjusting medications that affect the body weight Diabetes medications Antidepressants Weight loss medications Avoid weight promoting medications 27

Diabetes Medications and Body Weight List A List B 1 Identify Weight Gain Weight Neutral Weight Loss Significant Modest 2 Plan Pioglitazone SUs Glyburide Glipizide Insulin NPH Glargine Regular Aspart Lispro Glulisine SUs Glimepiride Glipizide XL Glinides Repaglinide Nateglinide Insulin Detemir Glulisine (PP) Metformin DPP 4 Inhibitors Sitagliptin Saxaglipitin Linagliptin glucosidase Inhibitors Acarbose Miglitol Colesevelam GLP 1 Analoges Exenatide Exenatide ER Liraglutide Pramlintide Bromocriptine 3 Change Stop, Reduce or Switch Continue Add

Results of Optimal Intensive Lifestyle Intervention (OILI) Changes in Metabolic & CV Outcomes 7.5 HbA1c (%) * 6.6 n = 115 * P<0.001 Before After Hamdy O, et al. Curr Diab Rep. 2008;8(5):413 420 29

Cost effectiveness of non surgical and surgical weight management Health Care Cost and Diabetes Related Cost Cost utilization (Hospitalization, Clinic visits) 30

Cost effectiveness of Intensive Lifestyle Intervention A 10 year analysis of the Diabetes Prevention Program trial showed lifestyle intervention was cost effective compared with placebo in prevention of diabetes in high risk adults From a payer perspective, investment in lifestyle management for diabetes prevention provides good value 31 The Diabetes Prevention Program Research Group. Diabetes Care. 2012;35:723-730.

Economic Impact of Non Surgical Weight Loss in One Year in Patients With Diabetes Cost Saving (1% wt loss) Estimated Saving with (7% wt loss) Cost saving per year (-3.6%) 1* (-5.8%) 2* (-44%) (-27%) Health Care Cost Diabetes Related Cost 1) p<0.5 2) p<001 YU AP et al. Curr Med Res Opin. 2007;23(9):2157-69 32

Impact of Bariatric Surgery on Healthcare Utilization & Costs in Patients with DM over 6 Years 7,806 patients with diabetes who received bariatric surgery Odds of Hospitalization Ratio of Counts of PCP Visits Ratio of Counts of Specialist Conclusion In the six years following bariatric surgery, individuals with type 2 diabetes did not have lower healthcare costs than before surgery. 33 Bleich SN et al. Med Care. 2012, 50(1):58-65

In Conclusion 1 2 3 4 5 Long-term weight reduction can be achieved through nonsurgical weight management Exercise type and duration significantly impact long-term weight maintenance Changing macronutrient compositions, providing structured meal plan plus adding calorie replacements are effective dietary intervention Adjusting diabetes medications is important for effective long-term weight reduction in patients with diabetes Long-term weight reduction is costeffective for prevention and treatment of diabetes 34