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

Abstract

ObjectiveHydrothermal 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).DesignEligible patients (haemoglobin A1c (HbA1c) 59–86 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.ResultsOverall 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 –6.6 mmol/mol (17.5 mmol/mol) versus –3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was –5.4% (6.1%) versus –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.ConclusionsDMR 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 numberNCT02879383

Endoscopic duodenal mucosal resurfacing for nonalcoholic steatohepatitis (NASH): a pilot study

“…Our study population differs from the recent published RE-VITA-2 randomized clinical trial (RCT) [19] in which DMR was shown to be associated with improvement in metabolic factors. First, a greater reduction in HbA1c was reported in patients with high baseline FPG (≥ 180 mg/d) which contrasts with the demographic data for our study population.…”

Non-alcoholic fatty liver disease: A patient guideline

“…Besides surgery, other techniques, such as endoscopic techniques, are under evaluation with the aim of reducing weight and/or improving metabolism (particularly diabetes). 226 Further studies are needed to confirm the efficacy of these techniques and to determine their role in combatting NAFLD.…”

“…The place of other treatment modalities, such as endoscopic 226 or surgical weight-reducing interventions, 208 is not clear and probably should follow the same principles as those for drug treatment. Of course, if such a procedure is indicated for an associated problem such as obesity and T2D, your liver could also benefit from this procedure, but liver disease cannot be considered the standalone reason to perform such a procedure.…”

Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases

“…Metabolic diseases can further be treated by duodenal mucosal resurfacing (DMR), an endoscopic technique to ablate the duodenal mucosa and thereby improve glycemic and weight control ( 180 ). As studies have further reported an improvement of glucose homeostasis and transaminase levels, a possible improvement of NASH is also assumed.…”