1. Simon Dexter Leeds Teaching Hospitals Trust

2. YearBand InsertionsRemovals 2006-0771511 2007-081,04445 2008-091,38246 2009-101,63882 2010-11 1,555125 2011-121,316124 YearNo. of gastric bypasses 2006-07858 2007-081,312 2008-092,533 2009-103,745 2010-114,722 2011-125,407 Health and Social Care Information Centre

9.  Mechanism of action

10. Obesity In utero programming Food choiceGenetics Physical activity Metabolic factors Macronutrient balance Appetite control mechnisms Endocrine causes Dietary factors Psychological factors

11. Obesity In utero programming Food choiceGenetics Physical activity Metabolic factors Macronutrient balance Appetite control mechnisms Endocrine causes Dietary factors Psychological factors

13.  Volume restriction  Malabsorption  Gut hormone changes  Vagal activation  Dumping  Altered taste & food cravings  Emotional wellbeing  Physical ability  Set point theory

15.  Metabolic surgery

16. Sjostrom et al (2004) NEJM

21.  Foregut Ghrelin, duodenal exclusion  Hindgut GLP-1, PYY release

25.  Novel procedures

26. SURGICAL PLACEMENT  Gastric electrical stimulation ENDOSCOPIC PLACEMENT  Endobarrier  Intragastric balloon  POSE

27.  6 months maximum  Weight loss 2 – 4 stone

30. The EndoBarrier System Anchor Nitinol Large proximal opening Barbs in each direction Retrieval drawstrings Liner Impermeable fluoropolymer 60 cm length Delivery System –Pre-loaded with implant –Sterile, single use Retrieval System –Endoscopic grasper, hood –Sterile, single use

32. 4 Long-term T2DM improvement with weight loss Delayed T2DM rebound post- removal Safety Second generation device Immediate T2DM improvement >500 Subjects 13 Studies Post-Marketing/Registry Experience

33.  Non-randomized, single arm  Single Center University of Sao Paulo (Sao Paulo, Brazil)  Planned duration - 52 weeks  Enrollment 22 subjects BMI=30-65 HbA1c=6-11.5%  1 week liquid diet followed by institution’s Bariatric standard of care diet

34. 12 Month Diabetes Study Reduction in HbA1c (n=13 completers) -1.9 Baseline HbA1c = 8.9% -2.3 1 Year Data 11/13 subjects HbA1c < 7% 6/11 subjects HbA1c < 7%

35. 12 Month Diabetes Study Improvement in Cardiovascular Risk Factors (n=13 completers) Baseline52 weeksp value Weight (kg)121.8 ± 7.6101.6 ± 5.7<.0001 BMI (kg/m 2 )45.3 ± 2.437.8 ± 1.8<.0001 Waist circumference (cm)131.6 ± 5.1119.9 ± 5.1<.0001 Total cholesterol (mg/dl) HDL LDL Triglycerides 205.4 ± 10.9 44.1 ± 3.7 121.8 ± 9.7 214.2 ± 27.2 177.3 ± 8.9 43.1 ± 4.4 104.4 ± 7.3 151.8 ± 14.2 0.0003 0.65 0.005 Glucose (mg/dl)174.9 ± 13.7137.8 ± 13.10.009 Insulin (uU/mg)21.1 ± 4.911.0 ± 1.50.034 HOMA IR8.6 ± 1.93.7 ± 0.60.023 HbA1c (%)8.9± 0.56.6 ± 0.3<.0001 Data presented as mean ± SE Compelling Impact on Key Risk Factors 1 Year Data

36. 12 Month Diabetes Study Reduction in HbA1c (n=13 completers) 1 Year Data 8.9% 6.6% 1 Year Data Mean Implant duration for all 22 subjects

37.  Non-randomized, single arm  Single Center Catolica University (Santiago, Chile)  Planned duration - 52 weeks  Treated 43 subjects BMI: 35.4-58.4  1 week liquid diet followed by institution’s Bariatric standard of care diet

38. 1 Year Data Baseline BMI = 45.2

39. Baseline52 weeksp value Weight (kg)112.4 ± 2.489.8 ± 3.2<.0001 BMI (kg/m 2 )45.3 ± 0.836.1 ± 1.1<.0001 Blood pressure (mmHg) Systolic Diastolic 134.0 ± 2.7 85.7 ± 1.3 124.7 ± 2.3 71.8 ± 1.8 0.003 <.0001 Total cholesterol (mg/dl) HDL LDL Triglycerides 195.1 ± 7.0 44.3 ± 1.7 119.9 ± 5.7 155.4 ± 14.2 159.6 ± 7.4 43.5 ± 1.5 93.9 ± 6.1 111.5 ± 10.0 <.0001 0.55 <.0001 0.001 Data presented as mean ± SE Compelling Impact on Key Risk Factors 1 Year Data 12 Month Obesity Study Improvement in Cardiovascular Risk Factors (n=27 completers)

40.  All devices removed endoscopically  Common Events Nausea, vomiting, abdominal pain  Rare Adverse Events GI hemorrhage, dehydration, constipation, diarrhea, hypoglycemia, vitamin or mineral deficiencies, liner obstruction

41.  Gastric neuromodulation Abiliti, Transcend - IGS  Gastric contractility modulation Diamond (Tantalus)  Vagal stimulation Vbloc

42.  Diamond (Tantalus) Gastric contractility modulation

44.  Induces satiety signalling via CNS  DM2 study HbA1c at baseline 7.8%  -1.0 @ 1 year  -1.1 @ 18/12 %EWL 24.6% @ 18/12

45. Consumption - ExpenditureWt Change = Gastric Stimulation Creates early sensation of satiety Reduces desire to eat between meals Reduced meal volume Patient Support System Tracks & reports eating events Tracks & reports exercise trends Useful diagnostic for sleep disorders Supports behavior modification Low Impact Excellent safety profile Minimal lifestyle changes No special diets No vitamin supplements IntraPace: Abiliti™

46. GSA102 Analyzer P102 Programmer W102 Programmer Wand LGS102 Stimulator LGL102 Lead IntraPace: abiliti™

47. Unpublished data Study Population Number of Subjects 30 Gender 25 Females / 5 Males Age (years) Mean, range 40 (20 to 60) Weight (lb) Mean, range 284.6 (213.4 to 370) Excess weight (lb) 124.6 (72.9 to 177.5) BMI Mean, range 43.8 (32.5 to 55)

48. Abiliti™: Weight Loss Unpublished data

49.  Bariatric surgery increasing  Better understanding of mechanisms of action  Metabolic role of surgery  Development of novel procedures