Slide 1: Duodenal Mucosal Resurfacing: A New Procedural Therapy for Type 2 Diabetes
Duodenal Mucosal Resurfacing A New Procedural Therapy for Type 2 Diabetes Safety and Proof-of-Principle First In Human Clinical Study IFSO 2014 Authors: Manoel Galvao Neto MD, Leonardo Rodriguez MD, Patricia Rodriguez RN, Pablo Becerra MD, Paolina Vignolo MD C.C.O – Clinica de Control de la Obesidad
Slide 2: Disclosure
Disclosure Manoel Galvao Neto MD, Leonardo Rodriguez MD, Patricia Rodriguez RN, Pablo Becerra MD, Paolina Vignolo MD This study was funded by Fractyl Laboratories Inc., Waltham, MA 2
Slide 3: Nutrient stimulation of duodenum worsens glucose homeostasis in diabetics post-RYGB
Nutrient stimulation of duodenum worsens glucose homeostasis in diabetics post-RYGB G-tube G-tube PO PO Dirksen et al 2010 What does this mean about mechanisms of RYGB-associated T2DM improvement? • Glucose improvement not primarily due to diet, weight loss, or caloric restriction • Must be mediated
Slide 4: Human duodenal biopsies and animal models show diabetic duodenal mucosal changes
Human duodenal biopsies and animal models show diabetic duodenal mucosal changes Duodenal biopsies from humans Duodenal samples from diabetic rats Theodorakis et al Gniuli et al
Slide 5: A model for Type 2 diabetes pathogenesis – intestinal hormonal changes may drive insulin resistance
A model for Type 2 diabetes pathogenesis – intestinal hormonal changes may drive insulin resistance Mucosal End-organ hypertrophy/ Decompensation Fat effects hyperplasia of pancreatic Hyperglycemia Sugar on muscle, change gut beta-cells liver, etc hormones
Slide 6: Duodenal mucosal abrasion can improve glucose tolerance in diabetic rats
Duodenal mucosal abrasion can improve glucose tolerance in diabetic rats 34% improvement in the OGTT after abrasion compared to sham treated rats Unpublished
Slide 7: Revita FIH Clinical Trial
Revita FIH Clinical Trial Trial Methodology: Procedural steps: Open label first-in-human › Duodenal sizing safety, feasibility, and proof- of-principle cohort study › Avoidance of papilla Dosimetric escalation (dose › Circumferential saline defined as axial length of expansion of submucosa circumfer
Slide 8: Revita FIH Patient Characteristics
Revita FIH Patient Characteristics Enrollment criteria: Characteristic Value T2DM < 10 yrs Age 28-75 Number 30 HbA1c 7.5-12% Female sex - N (%) 8 (38%) BMI 24-40 Age - yr 53.7 +/- 8.2 No previous bariatric surgery BMI 31.3 +/- 3.5 Preserved Baseline HbA1c (%) 9.3 +/- 1.4 pancreatic function Duration
Slide 9: DMR Procedural Video
DMR Procedural Video Revita is investigational and not yet approved for sale
Slide 10: Revita FIH Results
Revita FIH Results Baseline 1 month 3 months HbA1c Long segment 9.20 8.11 7.02 Short segment 9.19 9.10 9.66 Fasting glucose Long segment 186.5 -63.5 -67.2 change Short segment 193.3 -17.4 -16.4 Weight change Long segment 85.0 -4.3 -5.6 Short segment 86.6 -2.3 -0.6
Slide 11: Revita FIH Results
Revita FIH Results 19 patients @ 1 month 10 patients @ 3 months
Slide 12: Revita FIH Results
Revita FIH Results 19 patients @ 1 month 10 patients @ 3 months
Slide 13: Revita FIH Results / Up-to-Date Data
Revita FIH Results / Up-to-Date Data 30 patients @ 1 month 24 patients @ 3 months 8 patients @ 6 months
Slide 14: Revita FIH Results / Up-to-Date Data
Revita FIH Results / Up-to-Date Data
Slide 15: Adverse Events
Adverse Events Adverse Events (all Number 1 patient experienced transient) a duodenal stenosis Abdominal bloating 5 that was easily dilated Sore throat 2 Asymptomatic Duodenitis 2 with TTS CRE balloon. Abdominal muscle pain 2 Now doing well Right hip pain 1 No bleeding, Diarrhea 1 pancreatitis, duod
Slide 16: Conclusions
Conclusions Intriguing early data to support concept of duodenal mucosal resurfacing as a treatment for Type 2 Diabetes Safety profile is remarkably good Additional studies are warranted