Duodenal mucosal resurfacing (DMR) is safe and provides beneficial disease-modifying metabolic effects in patients with type 2 diabetes (T2D) with or without nonalcoholic fatty liver disease (NAFLD), according to a study in Gut.
The double-blind, multicenter, randomized controlled trial assessed the efficacy and safety of DMR in patients with T2D with or without NAFLD compared with a sham endoscopic procedure. The study was conducted from September 11, 2017, to December 15, 2018, in Europe and Brazil. DMR was performed with the single catheter Revitasystem (Revita DMR; Fractyl Laboratories).
The primary efficacy endpoints were the absolute change in hemoglobin A1c (HbA1c) from baseline to 24 weeks and absolute change from baseline to 12 weeks in liver magnetic resonance imaging proton density fat fraction (MRI-PDFF).
A total of 109 patients were randomly assigned 1:1 to DMR (n=56; mean age, 58.0 years; 69.6% men; 66.1% White) or to the sham procedure (n=52; mean age, 58.5 years; 69.2% men; 65.4% White); 75 patients were from Europe (39 DMR, 36 sham procedure), and 33 were from Brazil (17 DMR, 16 sham procedure); 1 patient did not receive treatment.
The median change in HbA1c from baseline to 24 weeks postprocedure was -10.4 mmol/mol in the DMR group vs -7.1 mmol/mol in the sham group (P =.147; treatment difference, -3.3 mmol/mol). In patients with baseline liver MRI-PDFF >5% (DMR, n=48; sham, n=43), the median absolute change in liver MRI-PDFF from baseline to 12 weeks was -5.4% in the DMR group vs -2.9% in the sham group (P =.096; treatment difference, -2.5%).
In interaction testing by region, heterogeneity was observed between patients in Europe (DMR, n=39; sham, n=36) and those in Brazil (DMR, n=17; sham, n=16) regarding HbA1c outcome (P =.063).
In the European patients, the median change in HbA1c from baseline to 24 weeks was -6.6 mmol/mol in the DMR group vs -3.3 mmol/mol in the sham group (P =.033; treatment difference, -3.3mmol/mol). In patients with baseline liver MRI-PDFF >5%, the median absolute change from baseline to 12 weeks was a decrease in liver fat content by 5.4% in the DMR group vs 2.2% in the sham group (P =.035; treatment difference, -3.2%).
In the Brazilian cohort, the change from baseline in HbA1c levels was not significantly different between the DMR group and the sham group in the primary analysis, but it was significantly lower in the prespecified sensitivity mixed-model repeated measures analysis (P =.104 and P =.034, respectively). No significant difference was observed between treatment groups in liver MRI-PDFF in the Brazilian cohort.
Post-hoc analysis of pooled data from the overall per-protocol population showed that among patients with fasting plasma glucose (FPG) ≥10 mmol/L, the median decrease in HbA1c at week 24 post-procedure was -14.2 mmol/mol post-DMR vs -4.4 mmol/mol in the sham group (P =.002). Among patients with FPG <10 mmol/L, the median decrease in HbA1c was comparable between the groups (P =.148).
In the safety analysis, about 33% of patients in the DMR group had a device-related or procedure-related adverse event of special interest (AESI) vs 27% in the sham group. Abdominal pain and hypoglycemia were the most frequently occurring (in ≥5% of patients) device-related or procedure-related AESIs at ≤30 days postprocedure.
Study limitations include the relatively small patient population and heterogeneity between European and Brazilian populations. Additionally, data on race were not obtained in the majority of the European patient population.
“These data provide insight into a potential therapeutic opportunity for duodenal mucosal resurfacing to favourably impact both type 2 diabetes and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in a manner that can modify the natural history of these chronic and progressive diseases,” the researchers commented.
Disclosure: This study was funded by Fractyl. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Mingrone G, van Baar ACG, Devière J, et al. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial. Gut. 2022;71(2):254-264. doi: 10.1136/gutjnl-2020-323608