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
PCOI Olympus Boston Scientific Cook Medical Dark Canyon Laboratory Merck
Objectives Understand the scope of obesity and clinical goals of bariatric interventions Review some potential endoscopic approaches to bariatric interventions Understand current clinical issues
Obesity Impacts Metabolic Diabetes HTN Lipid profile Steatosis Other impacts CAD, CVA, OSA, Joint disease Design (cars, clothes, furniture, etc..) CDC NCHS Brief 2012
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
Obesity in US CDC NCHS Brief 2012
US Obesity Trend CDC NCHS Brief 2012
Prevalence of Self-Reported Obesity Among U.S. Adults 15% <20% 20% <25% 25% <30% 30% <35% 35% BRFSS, 2011
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)
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
FDA Approved Devices PMA Lap-Band (Allergan) Realize Gastric Band (Ethicon) Garren-Edwards Gastric Bubble withdrawn from market
Bariatric Surgery (Medicare) AHRQ, 2012
Band Anatomy Stellato, GIE, 2003
Gastric Sleeve Anatomy
Gastric-bypass Anatomy
Weight Reduction Buchwald, JAMA, 2004
Diabetes Outcomes Buchwald, JAMA, 2004
Buchwald, JAMA, 2004
Surgical Outcomes Buchwald, JAMA, 2004
Weight Loss Duration Sjostrom, NEJM, 2004
Morbidity and Mortality AHRQ, 2012
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
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
Endoscopic Modalities Restrictive Procedures Space Occupying Evacuation PEG Sleeve Bypass Gastric-jejunal Duodenal-jejunal Endoscopic or TV Sleeve Pacers/neuromodulators
Bypass Sleeve (DJ) EndoBarrier (GI Dynamics) Duodenojejunal (60 cm) Malabsorptive barrier Blocks nutrients Prevents mixing with bile and pancreatic secretions
EndoBarrier Rodriguez et al, Surg Obs, 2008 12 patients, BMI 43 10 maintained (2 poor placement) 12 week EWL 23.6% 4/4 diabetics off meds Tarnoff et al, Surg Endo, 2009 25 patients 20 maintained 3 bled, 1 migration, 1 obstruction 12 week EWL 22%
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, 2010 30 patients prior to surgery (4 not placed) 22 patients with 12 week EWL 19% 7/8 with diabetes overall decrease in glucose levels
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
Bypass Sleeve (EJ) ValenTx Esophagojejunal Sleeve (120 cm) Malabsorptive barrier Blocks nutrients Prevents mixing
ValenTx Sandler et al, Surg Endo, 2010 24 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
New FDA Paradigm (brief) Benefit-risk paradigm for clinical trial design of obesity devices: FDA proposal Lerner et al. Surgical Endoscopy, in press
TBL in place of EWL for primary endpoint EWL likely needed for secondary endpoints
Gradated Benefit and Risk Increase risk with resulting requirements for increased efficacy and greater durability
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