Metabolic Interventions and the GI Tract: Issues

Transcription

1 Metabolic Interventions and the GI Tract: Issues Michael L. Kochman, M.D., AGAF Wilmott Family Professor of Medicine Vice-Chair of Medicine for Clinical Affairs University of Pennsylvania Health System

2 PCOI Olympus Boston Scientific Cook Medical Dark Canyon Laboratory Merck

3 Objectives Understand the scope of obesity and clinical goals of bariatric interventions Review some potential endoscopic approaches to bariatric interventions Understand current clinical issues

4 Obesity Impacts Metabolic Diabetes HTN Lipid profile Steatosis Other impacts CAD, CVA, OSA, Joint disease Design (cars, clothes, furniture, etc..) CDC NCHS Brief 2012

5 Self-Reported Obesity Among U.S. Adults in 2011 Definitions Obesity: Body Mass Index (BMI) of 30 or higher. Body Mass Index (BMI): A measure of an adult s weight in relation to his or her height, calculated using the adult s weight in kilograms divided by the square of his or her height in meters. CDC NCHS Brief 2012

6 Obesity in US CDC NCHS Brief 2012

7 US Obesity Trend CDC NCHS Brief 2012

8 Prevalence of Self-Reported Obesity Among U.S. Adults 15% <20% 20% <25% 25% <30% 30% <35% 35% BRFSS, 2011

9 Take-home points Threat to our health and healthcare system 2/3 of US population overweight 1.7 billion worldwide Most obese patients fail medical weight loss A modest reduction (10%) of excess weight will reduce co-morbidities Estimated 50 million eligible (BMI >30)

10 Endoscopic Interventions PROCEDURE CATEGORY Early Intervention Bridge to Surgery Metabolic Primary Revision PROCEDURE AIM Providing weight loss or stabilization in early-stage obese patients who do not yet qualify for traditional surgery Reducing the obesity-related operative risk for various bariatric and non-bariatric surgeries Primarily addressing co-morbid illness (e.g. diabetes) Endoscopic option for the traditional surgical population, with outcomes and risk profiles similar to those of current surgeries Repairing failed bariatric surgical procedures Ryou et al, GICNA, 2011

11 FDA Approved Devices PMA Lap-Band (Allergan) Realize Gastric Band (Ethicon) Garren-Edwards Gastric Bubble withdrawn from market

12 Bariatric Surgery (Medicare) AHRQ, 2012

13 Band Anatomy Stellato, GIE, 2003

14 Gastric Sleeve Anatomy

15 Gastric-bypass Anatomy

16 Weight Reduction Buchwald, JAMA, 2004

17 Diabetes Outcomes Buchwald, JAMA, 2004

18 Buchwald, JAMA, 2004

19 Surgical Outcomes Buchwald, JAMA, 2004

20 Weight Loss Duration Sjostrom, NEJM, 2004

21 Morbidity and Mortality AHRQ, 2012

22 Endoluminal Therapy Goals Endoscopic procedures without general anesthesia Less morbidity and cost Efficacious weight reduction and metabolic improvement Diabetes improvement may be viable target Weight loss may be less than surgery Therapy may either be durable, repetitive interval therapy, or single application for limited duration

23 Diabetes Bypass of small bowel appears to improve Type 2 Diabetes May be independent of weight loss or decreased food intake Intestinal diversions appears to improve glucose metabolism by gut hormone modulation

24 Endoscopic Modalities Restrictive Procedures Space Occupying Evacuation PEG Sleeve Bypass Gastric-jejunal Duodenal-jejunal Endoscopic or TV Sleeve Pacers/neuromodulators

25 Bypass Sleeve (DJ) EndoBarrier (GI Dynamics) Duodenojejunal (60 cm) Malabsorptive barrier Blocks nutrients Prevents mixing with bile and pancreatic secretions

26 EndoBarrier Rodriguez et al, Surg Obs, patients, BMI maintained (2 poor placement) 12 week EWL 23.6% 4/4 diabetics off meds Tarnoff et al, Surg Endo, patients 20 maintained 3 bled, 1 migration, 1 obstruction 12 week EWL 22%

27 EndoBarrier Escalona, et al, Surg Obs, 2010 Modified sleeve with an additional restrictor (8 dilated) 10 patients with 12 week EWL 40% Schouten et al, Ann Surg, patients prior to surgery (4 not placed) 22 patients with 12 week EWL 19% 7/8 with diabetes overall decrease in glucose levels

28 Sleeve Gersin et al, GIE, 2010 Prospective randomized controlled trial Pre-bypass placement 21 patients (26 sham controls) 13 (24) patients at 12 weeks AEs > 10% EWL 62% (17%) TWL 8.2 kg (2.1 kg) 3 bled, 2 pain, 2 N/V, 1 other

29 Bypass Sleeve (EJ) ValenTx Esophagojejunal Sleeve (120 cm) Malabsorptive barrier Blocks nutrients Prevents mixing

30 ValenTx Sandler et al, Surg Endo, patients, BMI 42 (implanted in 22) 17/22 indwelling for 12 weeks 12 week EWL 39.7% 7 patients off meds with normalization of glucose 4 others with abnormal AIC improved

31 New FDA Paradigm (brief) Benefit-risk paradigm for clinical trial design of obesity devices: FDA proposal Lerner et al. Surgical Endoscopy, in press

32 TBL in place of EWL for primary endpoint EWL likely needed for secondary endpoints

33 Gradated Benefit and Risk Increase risk with resulting requirements for increased efficacy and greater durability

34 Barriers FDA Safety and Efficacy Paradigm shift: can diabetes be a primary end-point? Insurers Less cost Efficacy and durability Hospitals/Physicians ROI, support services

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