Duodenum presents key target for type 2 diabetes therapy
Adults who underwent duodenal mucosal resurfacing had improved glucose response and insulin sensitivity that suggest positive effects of the procedure on beta-cell function and the liver, according to data accepted for presentation at the Endocrine Society Annual Meeting and delivered in a virtual press conference.
“We’ve come to learn over the years from the initial working on bariatric surgery [that] the duodenum mucosa, the cell lining that faces the lumen of the duodenum, is a very metabolically active and endocrine center and has a key role in the main regulation of insulin action,” David Hopkins, BSc(Hons), MBChB, MRCP, FRCP, a consultant in general medicine at King’s Health Partners in London, said during his presentation.
Revita DMR (Fractyl) is an outpatient procedure that takes about 45 minutes and involves inserting a catheter endoscopically along the wall of the duodenum, separating the mucosal lining. Hot water is then passed through the balloon of the catheter to ablate the lining.
“This results in immediate changes in the mucosa of the duodenum, which lead to it regressing to a less hypertrophied form over a very short time, over days,” Hopkins said.
In a substudy of Revita-2, a sham-controlled, double-blind, prospective multicenter study of the effects of the procedure on type 2 diabetes, Hopkins and colleagues performed duodenal resurfacing (n = 35) or a sham procedure (n = 35) on adults with diabetes (HbA1c 7.5%-10%; BMI 24 kg/m2-40 kg/m2) prescribed at least one diabetes medication; 57% and 54%, respectively, had fasting plasma glucose of at least 180 mg/dL at baseline.
At 24 weeks, the researchers noted significant reductions in HbA1c and liver fat on MRI “similar or better than had been seen in specific studies of tentative agents for management of fatty liver disease,” Hopkins said.
After mixed-meal tolerance tests at 12 weeks, FPG was reduced by –41 mg/dL from baseline for the duodenal resurfacing group vs. –15 mg/dL for the sham group (P = .009), driving a –36.38 mg/dL median reduction in area under the curve for glucose for the resurfacing group vs. –4.94 mg/dL for the sham group (P = .009).
In subgroup analyses of participants with baseline FPG of at least 180 mg/dL, those in the resurfacing group had a median AUC glucose reduction of –63.03 mg/dL vs. –20.31 for the sham group (P = .007). Similarly, those in the resurfacing group had an increased median postprandial C-peptide excursion (0.41 ng/mL) vs. the sham group (0.02 ng/mL; P = .012) and decreased postprandial glucagon: –8.03 pg/mL for the resurfacing group vs. 2.13 pg/mL for the sham group (P = .027).
“This is important because this series of data demonstrate improvements in insulin sensitivity with improvements in insulin secretion and reduction in glucagon, which is another key driver of a glucose dysregulation in diabetes,” Hopkins said.
In follow-up questions, Harith Rajagopalan, co-founder and CEO of Fractyl, developer of the Revita DMR procedure, told Healio that earlier studies did not suggest a relationship between baseline BMI and glucose or liver benefits, but that future studies would evaluate that question. – by Jill Rollet
Reference:
Hopkins D, et al. OR30-07. The Endocrine Society Annual Meeting; 2020 (conference canceled/virtual meeting).
Disclosures: Hopkins reports he has received honoraria for consultancy or speakers fees from AstraZeneca, Fractyl Laboratories, Novo Nordisk, Roche, Sanofi and Sunovion. Rajagopalan reports he is co-founder and CEO of Fractyl.