Duodenal mucosal intervention in the management of MASLD and type 2 diabetes

BACKGROUND: The pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) is rooted in the gut-liver axis dysfunction. To enhance glycemic control and liver fat level, new duodenal mucosal ablation procedures, such as duodenal mucosal resurfacing (DMR), recellularization via electroporation therapy (ReCET), and photodynamic therapy, seek to reset duodenal signaling in a less invasive manner. METHODS: A systematic review (2016-2024) was carried out. Both observational studies and randomized controlled trials (RCTs) assessing duodenal mucosal treatments in adult patients with T2DM and/or MASLD were included. Changes in liver fat, insulin resistance, fasting plasma glucose (FPG), HbA1c, and safety profiles were key outcomes of interest. RESULTS: The sham-controlled REVITA-2 RCT showed that DMR is safe and produces clinically significant metabolic benefits: at 12 weeks, liver fat (MRI-PDFF) decreased by 5.4% versus 2.2% (p = 0.035) and HbA1c reduced by 6.6 mmol/mol vesus 3.3 mmol/mol in the sham group(p = 0.033) among European participants. Without significant safety concerns, duodenal mucosal ablation procedures were found to lower HbA1c, FPG, and liver fat in 15 studies (n = 317), including seven DMR and two ReCET reports. These techniques also lead to insulin cessation in 86% of patients. CONCLUSION: Duodenal mucosal treatments, in particular DMR, appear to be viable minimally invasive approaches to treat the dual metabolic loads of T2DM and MASLD. Although long-term studies with histologic outcomes in MASLD are warranted to validate the efficacy and refine patient selection criteria, these methods seem safe and beneficial.