Prediabetes Management 1 AACE Prediabetes Consensus Statement Summary

Prediabetes Management 1

AACE Prediabetes Consensus Statement: Summary • Untreated individuals with prediabetes are at increased risk for diabetes as well as for micro- and macrovascular complications • Treatment goals are to prevent deterioration in glucose levels and modify other risk factors such as obesity, hypertension, and dyslipidemia – The same blood pressure and lipid goals are suggested for prediabetes and diabetes • Intensive lifestyle management is the cornerstone of all prevention efforts; pharmacotherapy targeted at glucose may be considered in high-risk patients Handelsman YH, et al. Endocr Pract. 2015; 21(suppl 1): 1 -87. Garber AJ, et al. Endocr Pract. 2008; 14: 933 -946. 2

Prediabetes • Epidemiologic evidence suggests that the complications of T 2 D begin early in the progression from NGT to frank diabetes • Prediabetes and diabetes are conditions in which early detection is appropriate, because – Duration of hyperglycemia is a predictor of adverse outcomes – There are effective interventions to prevent disease progression and to reduce complications NGT, normal glucose tolerance ; T 2 D, type 2 diabetes. Garber AJ, et al. Endocr Pract. 2008; 14: 933 -946. 3

Policy Paradigm Shifts Needed to Stem Global Tide of T 2 D • Integrating primary and secondary prevention along a clinical continuum • Early detection of prediabetes and undiagnosed diabetes • Implementing cost-effective prevention and control by integrating community and clinical expertise and resources within affordable service delivery systems • Sharing and adopting evidence-based policies at the global level T 2 D, type 2 diabetes. Narayan KM, et al. Health Aff (Millwood). 2012; 31: 84 -92. 4

Feasibility of Preventing Type 2 Diabetes • There is a long period of glucose intolerance that precedes the development of diabetes • Screening tests can identify persons at high risk • There are safe, potentially effective interventions that can address modifiable risk factors: – – Obesity Body fat distribution Physical inactivity High blood glucose Garber AJ, et al. Endocr Pract. 2008; 14: 933 -946. 7

Interventions to Reduce Risks Associated With Prediabetes • Therapeutic lifestyle management is the cornerstone of all prevention efforts • No pharmacologic agents are currently approved for the management of prediabetes – Pharmacotherapy targeted at glucose may be considered in high-risk patients after individual risk-benefit analysis Garber AJ, et al. Endocr Pract. 2008; 14: 933 -946. 8

Lifestyle Intervention in Prediabetes • Persons with prediabetes should reduce weight by 5% to 10%, with long-term maintenance at this level – A program of regular moderate-intensity physical activity for 30 -60 minutes daily, at least 5 days a week, is recommended – A diet that includes caloric restriction, increased fiber intake, and (in some cases) carbohydrate intake limitations is advised Garber AJ, et al. Endocr Pract. 2008; 14: 933 -946. Garber AL, et al. Endocr Pract. 2018; 24: 91 -120. 9

Primary Care-Based Counseling for T 2 D Prevention: ADAPT System for Behavior-Change Counseling Behavior-Change Principles Persuasive Psychology • • Patient-selected behavior-change goals Behavior-change props Implementation-intentions exercise Behavior-change prescription Social comparisons Behavior-change samples Testimonials Technology • Electronic record–based goalsetting tool with facilitated order entry and documentation • • Website-based tailored reminders Frequent feedback about progress via email ADAPT, Avoiding Diabetes Thru Action Plan Targeting; T 2 D, type 2 diabetes. Mann DM, Lin JJ. Implement Sci. 2012; 23: 6. 10

Self-Reported Risk Reduction Activities in Patients With Prediabetes National Health and Nutrition Examination Survey 100% 90% 80% 70% 68% 60% Patients 60% 55% 50% 42% 40% 30% 20% 10% 0% Tried to lose or control weight Reduced dietary fat Increased physical or calories activity or exercise CDC. MMWR Morb Mortal Wkly Rep. 2008; 57: 1203 -1205. All 3 11

Prediabetes Management PREVENTION OF DIABETES: LIFESTYLE STUDIES 12

Prevention of T 2 D: Selected Lifestyle Modification Trials Study Country N Baseline BMI (kg/m 2) Intervention period (years) RRR (%) NNT Diabetes Prevention Program USA 3234 34. 0 2. 8 58 21 Diabetes Prevention Study Finland 523 31 4 39 22 Da Qing China 577 25. 8 6 51 30 NNT, number needed to treat; RRR, relative risk reduction; T 2 D, type 2 diabetes. DPP Research Group. N Engl J Med. 2002; 346: 393 -403. Eriksson J, et al. Diabetologia. 1999; 42: 793 -801. Li G, et al. Lancet. 2008; 371: 1783 -1789. Lindstrom J, et al. Lancet. 2006; 368: 1673 -1679. 13

Intensive Lifestyle Intervention Effectively Prevents Progression From IGT to T 2 D Diabetes Prevention Program (N=3234) Diabetes Incidence per 100 Person-Years 12 11 10 8 6 31% 7, 8 58% 4, 8 4 2 0 Intensive lifestyle intervention* (n=1079) Metformin 850 mg BID (n=1073) Placebo (n=1082) *Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥ 150 min/week moderate intensity exercise. IGT, impaired glucose tolerance; T 2 D, type 2 diabetes. DPP Research Group. N Engl J Med. 2002; 346: 393 -403. 14

Lifestyle Intervention More Effectively Prevents Diabetes as Populations Age Diabetes Prevention Program (N=3234) Diabetes Incidence per 100 Person-Years 14 12 11, 6 10, 8 9, 6 10 8 6, 7 48% 6, 2 6 7, 6 Placebo 59% 71% 4, 7 3, 1 4 Metformin Lifestyle 2 0 25 -44 45 -59 Age (years) ≥ 60 *Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥ 150 min/week moderate intensity exercise. DPP Research Group. N Engl J Med. 2002; 346: 393 -403. 15

Effectiveness of Lifestyle Intervention for Diabetes Prevention Wanes as Weight Increases Diabetes Prevention Program (N=3234) Diabetes Incidence per 100 Person-Years 16 14, 3 14 12 10 9 51% 8, 9 8, 8 7, 6 8 7, 0 7, 3 Placebo 6 65% 61% Metformin 3, 7 Lifestyle 4 3, 3 2 0 22 to <30 30 to <35 BMI (kg/m 2) ≥ 35 *Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥ 150 min/week moderate intensity exercise. DPP Research Group. N Engl J Med. 2002; 346: 393 -403. 16

Maintenance of Long-Term Weight Loss DPP Outcomes Study (N=2766) 0 1 2 3 4 5 6 7 8 9 10 Years DPP, Diabetes Prevention Program; T 2 D, type 2 diabetes. DPP Research Group. Lancet. 2009; 374: 1677 -1686. 17

10 -Year Incidence of T 2 D DPP Outcomes Study (N=2766) Placebo Metformin Lifestyle 0 1 2 3 4 5 6 Years 7 8 9 10 DPP, Diabetes Prevention Program; T 2 D, type 2 diabetes. DPP Research Group. Lancet. 2009; 374: 1677 -1686. 18

10 -Year Incidence of Type 2 Diabetes DPP Outcomes Study DPP, Diabetes Prevention Program; DPPOS, Diabetes Prevention Program Outcomes Study; T 2 D, type 2 diabetes. DPP Research Group. Lancet. 2009; 374: 1677 -1686. 19

T 2 D Prevention in Women With a History of GDM • Findings from the DPP – Progression to diabetes is more common in women with a history of GDM vs those without, despite equivalent degrees of IGT at baseline • Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM DPP, Diabetes Prevention Program; GDM, gestational diabetes mellitus; IGT, impaired glucose tolerance; T 2 D, type 2 diabetes. Ratner RE, et al. J Clin Endocrinol Metab. 2008; 93: 4774 -4779. 20

Effect of Lifestyle Modification on Weight and Blood Pressure The Finnish Diabetes Prevention Study Control (n=250) Weight (kg) Waist (cm) Diet intervention (n=256) SBP (mm Hg) DBP (mm Hg) Change from baseline 0 -1 -2 -3 -4 -5 P<0. 001 -6 P<0. 001 P=0. 007 P=0. 02 DBP, diastolic blood pressure; SBP, systolic blood pressure. Tuomilehto J, et al. N Engl J Med. 2001; 344: 1343 -1350. 21

Effect of Lifestyle Modification on Glucose in Patients with IGT The Finnish Diabetes Prevention Study Control (n=250) Diet intervention (n=256) Change from baseline 10 0 -10 P<0. 001 P=0. 003 -20 -30 P=0. 001 -40 FPG (mg/d. L) 2 -h PG (mg/d. L) Fasting insulin (mg/m. L) 2 -h insulin ( g/m. L) IGT, impaired glucose tolerance. Tuomilehto J, et al. N Engl J Med. 2001; 344: 1343 -1350. 22

Cumulative Incidence of Diabetes Over 4 Years The Finnish Diabetes Prevention Study Control (n=250) Incidence of diabetes (cases/1000 person-years) 80 Diet intervention (n=256) 78 60 58% 40 32 20 0 DBP, diastolic blood pressure; SBP, systolic blood pressure. Tuomilehto J, et al. N Engl J Med. 2001; 344: 1343 -1350. 23

Cumulative Incidence of Diabetes in Asian Patients with IGT Da Qing Diabetes Prevention Study (N=577) Patients with T 2 D at Year 6 (%) Total 100 90 80 70 60 50 40 30 20 10 0 65, 9 Lean Overweight 72, 3 60 48 47, 1 38, 2 51, 2 44, 2 52, 5 44, 6 34, 8 26, 3 Control Diet Exercise Diet + Exercise IGT, impaired glucose tolerance; T 2 D, type 2 diabetes. Pan XR, et al. Diabetes Care. 1997; 20: 537 -544. 24

20 -Year Cumulative T 2 D Incidence in Asian Patients with IGT Da Qing Diabetes Prevention Study IGT, impaired glucose tolerance; T 2 D, type 2 diabetes. Li G, et al. Lancet. 2008; 371: 1783 -1789. 25

23 -Year All-Cause Mortality in Asian Patients with IGT Da Qing Diabetes Prevention Study IGT, impaired glucose tolerance. Li G, et al. Lancet Diabetes Endocrinol. 2014; 2: 474 -478. 26

23 -Year Cardiovascular Mortality in Asian Patients with IGT Da Qing Diabetes Prevention Study IGT, impaired glucose tolerance. Li G, et al. Lancet Diabetes Endocrinol. 2014; 2: 474 -478. 27

23 -Year Incidence of T 2 D in Asian Patients with IGT Da Qing Diabetes Prevention Study IGT, impaired glucose tolerance; T 2 D, type 2 diabetes. Li G, et al. Lancet Diabetes Endocrinol. 2014; 2: 474 -478. 28

Group Lifestyle Balance Program Intervention University of Pittsburgh Primary Care Practice and Diabetes Prevention Support Center Weight Loss > 3. 5% Weight Loss >7% • DPP lifestyle intervention adapted to a 12 -session groupbased program • Implemented in a community setting in 2 phases using a nonrandomized prospective design • Significant decreases in weight, waist circumference, and BMI noted in both phases vs baseline • Average combined weight loss for both groups over the 3 month intervention 70 Patients (%) 60 50 40 30 20 10 0 Phase 1 Post (n=51) Phase 2 Completers Phase 2 Post Both 6 mo (n=42) phases (n=67) Phase 2 12 mo • 7. 4 pounds (3. 5% relative loss, P<0. 001) DPP, Diabetes Prevention Program. Kramer MK, et al. Am J Prev Med. 2009; 37: 505 -511. 29

Translating the DPP Into Community Intervention The DEPLOY Pilot Study Total Cholesterol Total Weight (%) (mg/d. L) (N=92) 0 -2 -4 -6 -8 -1, 8 -2, 0 -6, 0 P=0. 008 P<0. 001 Standard 20 10 -6, 0 DPP 11, 8 6, 0 0 -10 -20 -13, 5 -21, 6 -30 P<0. 001 4 -6 months P=0. 002 12 -14 months DEPLOY, Diabetes Education & Prevention with a Lifestyle Intervention Offered at the YMCA; DPP, Diabetes Prevention Program; YMCA, Young Men’s Christian Association. Ackermann RT, et al. Am J Prev Med. 2008; 35: 357 -363. 30

Structured Programs Foster Adherence Montana Diabetes Control Program 16 -session program based on DPP-style intervention (N=355) 99 Mean weight (kg) 98 350 300 97 250 96 200 95 94 150 93 100 92 50 91 90 1 2 3 4 5 6 7 9 8 Week 10 11 12 13 14 15 16 Exercise per week (min) Mean weight Physical activity 7% weight loss goal 100 0 DPP, Diabetes Prevention Program. Amundson HA, et al. Diabetes Educ. 2009; 35: 209 -223. 31

Prediabetes Management PREVENTION OF DIABETES: PHARMACOTHERAPY AND SURGICAL STUDIES 32

Medical and Surgical Interventions Shown to Delay or Prevent T 2 D Follow-up Period Reduction in Risk of T 2 D (P value vs placebo) Metformin 1 2. 8 years 31% (P<0. 001) Acarbose 2 3. 3 years 25% (P=0. 0015) Pioglitazone 3 2. 4 years 72% (P<0. 001) Rosiglitazone 4 3. 0 years 60% (P<0. 0001) Orlistat 5 4 years 37% (P=0. 0032) Phentermine/topiramate 6 2 years 79% (P<0. 05) Bariatric surgery 7 10 years 75% (P<0. 001) Intervention Antihyperglycemic agents Weight loss interventions T 2 D, type 2 diabetes. 1. DPP Research Group. N Engl J Med. 2002; 346: 393 -403. 2. STOP-NIDDM Trial Research Group. Lancet. 2002; 359: 2072 -2077. 3. Defronzo RA, et al. N Engl J Med. 2011; 364: 1104 -15. 4. DREAM Trial Investigators. Lancet. 2006; 368: 1096 -1105. 5. Torgerson JS, et al. Diabetes Care. 2004; 27: 155 -161. 6. Garvey WT, et al. Diabetes Care. 2014; 37: 912 -921. 7. Sjostrom L, et al. N Engl J Med. 2004; 351: 2683 -2693. 33

The Effect of Metformin on the Progression of IGT to Diabetes Mellitus Incidence of Diabetes (%/yr) The Chinese Prevention Study (N=321) 65% Control Metformin IGT, impaired glucose tolerance; RRR, relative risk reduction. Yang W, et al. Chin J Endocrinol Metab. 2001; 17: 131 -136. 34

Effect of Lifestyle Modification and Metformin on Cumulative Diabetes Incidence 3 -y Cumulative Incidence (%) The Indian DPP (N=531) 29% Control (n=136) 26% 28% P=0. 02 P=0. 03 P=0. 02 Lifestyle Modification (n=133) Metformin (n=133) Lifestyle Modification + Metformin (n=129) DPP, Diabetes Prevention Program; LSM, lifestyle modification; MET, metformin; RRR, relative risk reduction. Ramachandran A, et al. Diabetologia. 2006; 49: 289 -297. 35

Effect of Acarbose on Reversion of IGT to NGT STOP-NIDDM P<0. 0001 40 35 35, 3 30, 9 Patients (%) 30 25 20 15 10 5 0 Placebo (n=715) Acarbose (n=714) IGT, impaired glucose tolerance; NGT, normal glucose tolerance; STOP-NIDDM, Study to Prevent Non-Insulin Dependent Diabetes Mellitus. Chiasson JL, et al. Lancet. 2002; 359: 2072 -2077. 36

Effect of Rosiglitazone on New-Onset Diabetes or Death in Patients with Prediabetes DREAM 0. 6 Placebo Cumulative hazard rate 0. 5 0. 4 60% 0. 3 0. 2 Rosiglitazone 0. 1 0. 0 0 1 2 3 4 1148 1310 177 217 Follow-up (years) No. at risk Placebo Rosiglitazone 2634 2635 2470 2538 2150 2414 DREAM, Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication. DREAM Trial Investigators. Lancet. 2006; 368: 1096 -1105. 37

Effect of Pioglitazone on Development of T 2 D in Patients with IGT ACT NOW Kaplan-Meier plot of Hazard Ratios for Time to Development of T 2 D ACT NOW, Actos Now for the Prevention of Diabetes; IGT, impaired glucose tolerance; T 2 D, type 2 diabetes. Defronzo RA, et al. N Engl J Med. 2011; 364: 1104 -1115. 38

Special Considerations for Thiazolidinedione Use in Patients With Prediabetes • Because of the known adverse effects of the TZDs, these agents should be considered only for patients at the greatest risk of developing future diabetes and those failing more conventional therapies Garber AL, et al. Endocr Pract. 2018; 24: 91 -120. 39

Effects of Exenatide and Lifestyle Modification on Body Weight and Glucose Tolerance in Obese Patients With and Without Prediabetes • Patients – N=152, weight 108. 6 +/- 23. 0 kg, BMI 39. 6 +/- 7. 0 kg/m 2 (IGT or IFG 25%) • Design – 24 -week randomized controlled trial: exenatide or placebo plus lifestyle intervention • Results: – Exenatide-treated patients lost 5. 1 kg from baseline vs 1. 6 kg with placebo (P<0. 001) – Both groups reduced their daily caloric intake – IGT or IFG normalized at end point in 77% and 56% of exenatide and placebo subjects, respectively BMI, body mass index; IFG, impaired fasting glucose; IGT, impaired glucose tolerance. Rosenstock J, et al. Diabetes Care. 2010; 33: 1173 -1175. 40

Effect of Lorcaserin on Body Weight in Obese Adults Over 2 Years BLOOM Study Smith SR, et al. N Engl J Med. 2010; 363: 245 -256. 41

Effect of Lorcaserin on Progression to T 2 D Proportion of BLOOM and BLOSSOM Patients With Newly Diagnosed Diabetes After 52 Weeks of Treatment Patients with A 1 C ≥ 6. 5% (%) 5 4 P=0. 003 3 2 1 0 Placebo Lorcaserin T 2 D, type 2 diabetes. Lorcaserin hydrochloride briefing document for FDA Advisory Committee. Woodcliff Lake, NJ: Eisai Inc. ; 2012. Available at: http: //www. fda. gov/downloads/Advisory. Committees/Committees. Meeting. Materials/Drugs/Endocrinologicand. Metabolic. Drugs. Advisory. C ommittee/UCM 303200. pdf. 42

Effect of Lorcaserin on Cardiometabolic Risk Markers BLOOM Study Risk Factors (Mean % Weight Loss) Lorcaserin 10 mg (5. 8%) Systolic BP, mm. Hg -1. 4 0. 04 Diastolic BP, mm. Hg -1. 1 0. 01 Triglycerides, % -6. 15 <0. 001 Total cholesterol, % -0. 90 0. 001 LDL-C, % 2. 87 0. 049 HDL-C, % 0. 05 NS hs. CRP, mg/L -1. 19 <0. 001 Fibrinogen, mg/d. L -21. 5 0. 001 P value* *P values represent comparisons to placebo. Intent to treat, last observation carried forward analysis for total study population. Smith SR, et al. N Engl J Med. 2010; 363: 245 -256. 43

Effect of Phentermine/Topiramate ER on Weight Loss in Obese Adults Over 2 Years SEQUEL Study (Completer Analysis) Placebo LS mean weight loss (%) 0 Phen/TPM ER 7. 5/46 Phen/TPM ER 15/92 -2 -4 -6 -8 -10 -12 -14 -16 CONQUER Trial 0 12 Placebo n: 227 Phen/TPM 7. 5/46 n: 153 Phen/TPM 15/92 n: 295 20 28 36 227 152 295 SEQUEL Extension 44 52 227 153 295 60 68 Weeks 76 84 208 137 268 92 100 108 LOCF 197 129 248 227 153 295 Data are shown with mean (95% CI). Phen/TPM ER, phentermine/topiramate extended release. Garvey WT, et al. Am J Clin Nutr. 2012; 95: 297 -308. 44

Effects of Phentermine/Topiramate ER on Glucose, Insulin, and Progression to T 2 D SEQUEL Study (N=675) Glucose and Insulin Fasting 2 -h OGTT 0 -5 -3, 6 -5, 4 * -15 -7, 2 -18 -39 -10, 8 * -25 0 -100 -200 -300 -400 3, 7 4 -18 * -37 -157 -264 * Placebo Progressors per year (%) Insulin (pmol/L) Glucose (mg/d. L) 5 Annualized Incidence of T 2 D 3, 5 54% 3 P=NS 76% 1, 7 P=0. 008 2, 5 2 1, 5 0, 9 1 0, 5 0 -327 Placebo * Phen/TPM ER 7. 5/46 mg Phen/TPM CR 7. 5/46 mg 15/92 mg Phen/TPM ER 15/92 mg *P≤ 0. 005 vs placebo. NS, not significant; Phen/TPM ER, phentermine/topiramate extended release; T 2 D, type 2 diabetes. Garvey WT, et al. Am J Clin Nutr. 2012; 95: 297 -308. 45

Effects of Phentermine/Topiramate ER in Patients at High Risk of Developing T 2 D SEQUEL Prediabetes/Metabolic Syndrome Cohort (N=475) Placebo* Phen/TPM ER 7. 5/46 mg* Annualized incidence rate of T 2 D 7 Phen/TPM ER 15/92 mg* 6, 4 6 5 4 3 3, 5 49% P=NS 89% 1, 8 P=0. 013 2 1 0 77% 80% P=0. 009 P<0. 001 1, 5 1, 3 0, 4 Prediabetes (n=316) Metabolic syndrome (n=451) *All groups had lifestyle intervention. NS, not significant; Phen/TPM ER, phentermine/topiramate extended release; T 2 D, type 2 diabetes. Garvey WT, et al. Diabetes Care. 2014; 37: 912 -921. 46

Relationship Between Weight Loss and Prevention of Type 2 Diabetes SEQUEL Prediabetes/Metabolic Syndrome Cohort (N=475) ITT-LOCF Analysis Annualized incidence rate of T 2 D 8 7 6 5 4 3 2 1 0 <5 ≥ 5 to <10 ≥ 10 to <15 ≥ 15 Magnitude of Weight Loss (%) ITT, intent to treat; LOCF, last observation carried forward. Garvey WT, et al. Diabetes Care. 2014; 37: 912 -921. 47

Effect of Phentermine/Topiramate ER on Cardiometabolic Risk Markers CONQUER Study Risk Factors (Mean % Weight Loss) Phentermine/ Topiramate ER 7. 5/46 mg (8. 4%) P value* Phentermine/ Topiramate ER 15/92 mg (10. 4%) P value* Systolic BP, mm. Hg -4. 7 0. 0008 -5. 6 <0. 0001 Diastolic BP, mm. Hg -3. 4 NS -3. 8 0. 0031 Triglycerides, % -8. 6 <0. 0001 -10. 6 <0. 0001 Total cholesterol, % -4. 9 0. 0345 -6. 3 <0. 0001 LDL-C, % -3. 7 NS -6. 9 0. 0069 HDL-C, % 5. 2 <0. 0001 6. 8 <0. 0001 hs. CRP, mg/L -2. 49 <0. 0001 Adiponectin, g/m. L 1. 40 <0. 0001 2. 08 <0. 0001 *P values represent comparisons to placebo. Intent to treat, last observation carried forward analysis for total study population. Gadde KM, et al. Lancet. 2011; 377: 1341 -1352. 48

Effects of Liraglutide in Obese Patients SCALE Obesity (N=3731) Weight (%) Weight Change After 56 Weeks 4 2 0 -2 -4 -6 -8 -10 -12 -14 -16 Pi-Sunyer X, et al. N Engl J Med. 2015; 373: 11 -22. Liraglutide (n=2437) Placebo (n=1225) -2, 6 -8 P<0. 001 49

Effects of Liraglutide in Obese Patients with Prediabetes SCALE Obesity and Prediabetes (N=3731) Patients with Prediabetes After 56 Weeks Weight Change After 56 Weeks Liraglutide 3 mg Placebo -2 -2, 8 -4 -6 -8 -10 -8, 4 * Patients (%) Weight (kg) 0 80 70 60 50 40 30 20 10 0 67, 3 * 30, 8 * 20, 7 7, 2 Normoglycemia at screening Prediabetes at screening *P<0. 001 vs placebo. Pi-Sunyer X, et al. N Engl J Med. 2015; 373: 11 -22. 50

Effect of Bariatric Surgery on Incidence of Type 2 Diabetes Swedish Obesity Study Carlsson LM, et al. N Engl J Med. 2012; 367: 695 -704. 51

Effect of Different Bariatric Surgeries on Weight-Related Comorbidities at 1 Year ACS Bariatric Surgery Center Network Prospective Observational Study (N=28, 616) Patients with resolution or improvement of condition (%) LAGB 90 83 † 68 80 ‡ 55 70 60 50 44 LSG* LRYGB 79 † 62 66 44 40 33 ‡ 35 66 64 70 ‡ 50 38 30 20 10 0 Diabetes Hypertension Hyperlipidemia Sleep apnea GERD *Small numbers of patients with 1 year of follow-up for all comorbidities (n≤ 38). †P<0. 05 vs LAGB; ‡P<0. 05 vs LRYGB. ACS, American College of Surgeons; BMI, body mass index; GERD, gastroesophageal reflux disease; LAGB, laparoscopic adjustable gastric band; LSG, laparoscopic sleeve gastrectomy; LRYGB, laparoscopic Roux-en-Y gastric bypass. Hutter MM, et al. Ann Surg. 2011; 254: 410 -420. 52