Slide 1: Disclosure of Conflicts of Interest
Disclosure of Conflicts of Interest I herewith declare the following paid or unpaid consultancies, business interests or sources of honoraria payments for the past three years, and anything else which could potentially be viewed as a conflict of interest: Unrestricted study grant provided by Fractyl
Slide 2: Duodenal mucosal resurfacing combined with GLP-1RA may eliminate insulin treatment in type 2 diabetes
Duodenal mucosal resurfacing combined with GLP-1RA may eliminate insulin treatment in type 2 diabetes while improving glycaemic control and metabolic health S. Meiring1 , A.C.G. van Baar1, P. Smeele1, T. Vriend2, F. Holleman3, M.R. Soeters3, J.G.P. Tijssen4, M. Nieuwdorp5, J.J.G.H.M. Bergman1 1Gastr
Slide 3: Target the duodenum for treatment of T2D
Target the duodenum for treatment of T2D Bypassing duodenum improves insulin resistance
Slide 4: How does DMR work? Revita Duodenal Mucosal Resurfacing Procedure
‘Aten How does OR work? Revita™ Duodenal Mucosal Resurfacing Procedure Dewees. The ideo behind Duodenal Mucosal Resurfacing, or DMR isto cause regeneration ofthe duodenal mucosa and restore the disturbed enteroendocrine signaling - Stet death gy SiMe rte aging erin ego knee omer [At the distal tip o
Slide 5: How does DMR work?
How does DMR work? • Improves insulin sensitivity (hallmark of T2D and metabolic syndrome) • First-in-human study in Chile (n=39) • Multicentre study in Europe (n=46) • In T2D patients on oral medication • HbA1c decrease of 10 mmol/mol (≈comparable to 1 oral drug)1 • Sustained at 24 months UEGW 2020
Slide 6: INSPIRE study
INSPIRE study • Single arm, single center, open-label • Intervention triangle: • Amsterdam Universitair Medisch Centrum • 16 patients 1. DMR procedure • Insuline stopped at day of DMR • 2 weeks post-procedural diet • Inclusioncriteria: 2. GLP-1 (Victoza, liraglutide) • Type 2 diabetes 1. Start 2 wee
Slide 7: INSPIRE study
INSPIRE study Follow-up: Every 4-12 weeks • Lifestyle counseling • Blood collection: • HbA1c ≤ 58 mmol/mol => Continue GLP-1RA • HbA1c > 58 mmol/mol => Stop GLP-1RA and restart insulin • Primary endpoint: • % of patients off insulin at 6 months with adequate glycaemic control (HbA1c ≤ 58 mmol/mol) •
Slide 8: Baseline characteristics
Patient characteristics (N=16) Age [years] 61 Baseline Male gender, n (%) 10 (63%) characteristics Duration of T2D [years] 11 Weight [kg] 87.5 BMI [kg/m2] 29.2 HbA1c [mmol/mol] 58 Fasting plasma glucose [mmol/l] 10.1 C-peptide [nmol/l] 0.70 HOMA-IR 8.1 Antidiabetic medication Mean number of daily un
Slide 9: Primary endpoint
Primary endpoint; Responders : HbA1c < 59 mmol/mol UEGW 2020
Slide 10: Despite elimination of insulin, improved glycaemic parameters
Despite elimination of insulin, improved glycaemic parameters Responders 6 months ( n=12) 12 months (n=9) Baseline 6 months p-value 12 months p-value HbA1c [%] 7.4 (7.1-7.6) 6.7 (6.6-7.3) 0.009 6.7 (6.5-7.2) 0.024 HOMA-IR 8.9 (4.5-13.3) 2.6 (1.4-4.1) 0.004 7.1 (6.7-7.7) 0.008 FPG [mmol/l] 10.5 (9.2-
Slide 11: Improved metabolic parameters
Improved metabolic parameters Responders 6 months ( n=12) 12 months (n=9) BMI [kg/m2] 29.8 (26.5-34.2) 27.2 (23.4-31.9) 0.002 25.5 (22.1-29.5) 0.008 Liver fat [%] 8.1 (5.1-13.2) 4.6 (2.4-11.0) 0.016 6.0 (2.7-10.9) 0.208 Complete study population 6 months(N=16) 12 months(n=16) BMI [kg/m2] 29.2 (26.5-
Slide 12: Conclusion
Conclusion • Single endoscopic DMR, combined with GLP-1 and lifestyle counseling, can eliminate insulin therapy in a subset of T2D patients… • …while improving parameters of glycaemia • …while improving overall metabolic health • The effect slightly fades after 12 months, but majority is off insulin
Slide 13: Limitations
Limitations • Uncontrolled pilot study with limited sample size • Contribution of each of the individual treatment components unknown • Data must be confirmed by new multicenter RCT • Mechanism of DMR not yet completely clear • Results of mechanistic studies will follow soon UEGW 2020