@article {Mingronegutjnl-2020-323608, author = {Geltrude Mingrone and Annieke CG van Baar and Jacques Devi{\`e}re and David Hopkins and Eduardo Moura and Cintia Cercato and Harith Rajagopalan and Juan Carlos Lopez-Talavera and Kelly White and Vijeta Bhambhani and Guido Costamagna and Rehan Haidry and Eduardo Grecco and Manoel Galvao Neto and Guruprasad Aithal and Alessandro Repici and Bu{\textquoteright}Hussain Hayee and Amyn Haji and A John Morris and Raf Bisschops and Manil D Chouhan and Naomi S Sakai and Deepak L Bhatt and Arun J Sanyal and J J G H M Bergman}, editor = {, and , and Grecco, Eduardo and Santomauro, Ana Teresa and Bergman, Jacques and Nieuwdorp, Max and Morris, John and Drummond, Russell and Carty, David and Devi{\`e}re, Jacques and Crenier, Laurent and Moura, Eduardo and Cercato, Cintia and Repici, Alessandro and Lania, Andrea and Betella, Nazerena and Hopkins, David and Hayee, Bu and Haji, Amyn and Ragunath, Krish and Idris, Iskander and Chee, Carolyn and Mingrone, Geltrude and Costamagna, Guido and Guidone, Caterina and Haidry, Rehan and Batterham, Rachel and Bisschops, Raf and Mertens, Ann}, title = {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}, elocation-id = {gutjnl-2020-323608}, year = {2021}, doi = {10.1136/gutjnl-2020-323608}, publisher = {BMJ Publishing Group}, abstract = {Objective Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D).Design Eligible patients (haemoglobin A1c (HbA1c) 59{\textendash}86 mmol/mol, body mass index>=24 and <=40 kg/m2, fasting insulin \>48.6 pmol/L, >=1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks.Results Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF \>5\% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)\% in DMR group versus -2.9 (6.2)\% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was {\textendash}6.6 mmol/mol (17.5 mmol/mol) versus {\textendash}3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was {\textendash}5.4\% (6.1\%) versus {\textendash}2.2\% (4.3\%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)>=10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient.Conclusions DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG.Trial registration number NCT02879383}, issn = {0017-5749}, URL = {https://gut.bmj.com/content/early/2021/03/02/gutjnl-2020-323608}, eprint = {https://gut.bmj.com/content/early/2021/03/02/gutjnl-2020-323608.full.pdf}, journal = {Gut} }