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Leveraging Weight Loss in the Treatment of Type 2 Diabetes

This article discusses the benefits of intentional weight loss in reducing mortality rates and improving cardiovascular health in individuals with Type 2 Diabetes. It also explores the challenges of weight loss in diabetic patients compared to non-diabetic individuals.

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Leveraging Weight Loss in the Treatment of Type 2 Diabetes

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  1. Leveraging Weight Loss in the Treatment of Type 2 Diabetes Part 2 of 4

  2. Intentional Weight Loss Reduces Mortality All Causes CVD + Diabetes 50 45.6 • Intentional loss resulted in a Relative Risk Reduction† of: • 22% ↓ all-cause death • 24% ↓ death from CVD + diabetes 40.3 40 33.6 31.4 31.8 30 26.1 Age-Adjusted Death Rate* 20 10 0 No Change UnintendedGain IntentionalLoss *Mortality rates are directly age-standardized to the age distribution of the cohort and expressed per 1000 person-years. †Adjusted for age, sex, initial BMI. Williamson DF, et al. Diabetes Care. 2000;23:1499-1504.

  3. Obese Individuals With Diabetes Have Difficulty Losing Weight Compared With Obese Nondiabetic Individuals With Behavioral Weight Control Program 0 Diabetic Individuals Nondiabetic Individuals -5 -10 Change of Ideal Weight (%) P<.01 -15 -20 -25 Baseline 5 10 15 20 Week Wing RR, et al. Diabetes Care. 1987;10:563-566.

  4. Body Weight Over 2 Years of Lifestyle Intervention Control Diet + Exercise 100 96 92 Weight (kg) 88 84 0 6 12 18 24 Months Wing RR, et al. Diabetes Care. 1998;21:350-359.

  5. Look AHEAD: Study Objective and Design Objective: Examine the long-term effects of an Intensive Lifestyle Intervention (ILI)on the incidence of major cardiovascular disease events Intensive Lifestyle Intervention (ILI) • Toolbox approach • Diet modification and caloric restriction • Increased physical activity • Weekly followed by bimonthlygroup meetings • Monthly one-on-one counseling sessions 2-Week Prerandomization N=5145 Age 45-74 Yearswith type 2 diabetes and BMI >25 kg/m2 • Self-monitoring of diet and physical activity • 1 diabetes education session Diabetes Support and Education (DSE) • Access to 3 additional group education sessions • No weigh-in at meetings and no behavioral strategy counseling The Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383.

  6. ILI DSE Look AHEAD: Changes in Weight and A1C Insulin Users Non-Users A1C Weight 0 0 -0.14 -0.7 -0.64* -2 -2 -4 -4 Change (%) Percent Weight Change (%) -6 -6 -7.6 -8 -8 -8.7† -8.6* -10 -10 *P<.001. †P=.002. Data % Mean ± SD. The Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383.

  7. Look AHEAD: Changes in Risk Factors Triglycerides Systolic BP LDL HDL 5 0 1.4 3.4* -2.8 -5 -5.2 -5.7† -6.8* -10 Change (%) -15 -14.6 -20 -25 -30 DSE ILI -30.3* *P<.001. †P=.49. Data % Mean ± SD. The Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383.

  8. ILI DSE Look AHEAD: Change in Percent Reaching Goal 30 26.4* 25 20 15.1* 15 Change (%) 12.8* 10 8.0 7.0 6.7† 6.5 5.4 5 0 BP(<130/80 mm Hg) All 3 Goals A1C (<7%) LDL(<100 mg/dL) *P<.001; †P=.34; Data % Mean ± SD. The Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383.

  9. Weight Loss Is Important in the Management of Type 2 Diabetes • Moderate weight loss improves glycemic control and reducescardiovascular disease risk in individuals with type 2 diabetes1 • 12-Year American Cancer Society Mortality Study:Prospective 12-year ACS mortality and weight loss substudy of 4970 diabetic individuals2 • Intentional weight loss ► 25% reduced mortality risk • 10% to 15% or 20 to 29 lb loss ► 33% reduced mortality risk • Meta-analysis:Multiple weight loss and mortality studies in ~2800 diabetic individuals3 • Intentional weight loss ► 25% reduced mortality risk 1. Klein S. Am J Clin Nutr. 2004;80:257-263.2. Williamson DF, et al. Diabetes Care. 2000;23:1499-1504. 3. Poobalan AS, et al. Obes Rev. 2007;8(6):503-513.

  10. Side Effects of Oral Agents: Weight Gain Oral Antidiabetic Agent* Weight Change (kg) -3.8 - 0.5 Metformin1-3 -0.2 - 4.3 Sulfonylureas1-4 0.9 - 4.6 Thiazolidinedimes4-6 0.3 - 3.0 Meglitinides4,7,8 -0.3 - 1.9 Metformin + Sulfonylurea1-3 0.8 - 2.1 Metformin + Thiazolidinedimes4-6 Sitagliptin10 No increase from baseline - 5 - 4 - 3 - 2 - 1 0 1 2 3 4 5 *Data are not from head-to-head studies. 1. Bristol-Myers Squibb. Metformin HCI Full Prescribing Information. 2006. 2. Bristol-Myers Squibb. Glyburide/Metformin HCI Full Prescribing Information. 2006. 3. Bristol-Myers Squibb. Glipizide/Metformin HCI Full Prescribing Information. 2007. 4. Malone M. Ann Pharmacother. 2005;39:2046-2055. 5. Takeda. Pioglitazone HCI Full Prescribing Information. 2007. 6. GlaxoSmithKline. Rosiglitazone maleate Full Prescribing Information. 2008. 7. Novartis. Nateglinide Full Prescribing Information. 2006. 8. Novo Nordisk. RepaglinideFull Prescribing Information. 2006. 9. GlaxoSmithKline. Rosiglitazone maleate/Metformin HCI Full Prescribing Information. 2007.10. Merck & Co., Inc. Sitagliptin Full Prescribing Information. 2007. -

  11. 11 10 9 8 7 -2.2% -2.1% -0.8% -1.4% -1.3% -2.1% -2.1% 6 5 +19.2 lb 20 16 +12.6 lb +10.4 lb +10.1 lb 12 +8.6 lb +6.2 lb +6.6 lb 8 +4.2 lb 4 0 Yki-Jarvinen et al2 Henry et al4 Riddleet al1 Holman et al3 Holman et al3 Holman et al3 Yki-Jarvinen et al2 Riddle et al1 All Insulin Regimens Improve Glycemic Control, but Often With Weight Gain Landmark Insulin Studies in Which Exenatide Was Not a Comparator -2.6% A1C (%) ADA GOAL Intensive Insulin Biphasic Insulin Prandial Insulin BID Insulin BASAL Insulin ∆ Weight (lb) 1. Riddle MC, et al. Diabetes Care. 2003;26:3080-3086. 2. Yki-Jarvinen H, et al. Ann Intern Med. 1999;130:389-396. 3. Holman RR. N Engl J Med. 2007;357:1716-1730. 4. Henry RR, et al. Diabetes Care. 1993;16:21-31.

  12. 5 Insulin-naive Previously insulin-treated 4 3 2 1 0 Combination Therapy With Insulin: Weight Gain Weight Gain (kg/1% decrease in A1C) GLIT MET SU MET SU SU+MET GLIT = glitazone; MET = metformin; SU = sulfonylurea. Yki-Jarvinen H. Diabetes Care. 2001;24:758-767.

  13. Potential Causes of Weight Gain With Treatment of Type 2 Diabetes • Improved glycemic control • Fear of, or treatment for, hypoglycemia • Increased appetite • Catch-up from weight-loss pretreatment • Weight gain with insulin treatment • Correlates with insulin dose • Mean weight gain 3.2 - 4.4 kg per 1% reduction in A1C • About ⅔ adipose tissue and ⅓ lean body mass Westphal SA, et al. Insulin. 2007;2:31-36.

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