Highlight
The ENDO trial, a large multicenter double-blind randomized sham-controlled study, showed that the EndoBarrier duodenal-jejunal bypass liner (DJBL) significantly reduced HbA1c by 1.1% at 12 months compared to a minimal reduction of 0.28% in the sham group. The device also facilitated clinically meaningful weight loss (7.7% total weight loss vs 2.1% in sham) and increased the proportion of patients achieving HbA1c ≤7% and weight loss ≥5%. Device-related serious adverse event rate was 9.4%, with some events requiring early device removal.
Study Background and Disease Burden
Type 2 diabetes mellitus (T2DM) complicated by obesity presents a significant therapeutic challenge worldwide due to its high prevalence, progressive course, and associated comorbidities. Despite optimized medical therapy and lifestyle modifications, many patients exhibit poor glycemic control, increasing their risk of microvascular and macrovascular complications. Bariatric surgery remains the most effective metabolic treatment but is invasive and not suitable or acceptable for all patients. Endoscopic interventions, such as the DJBL, offer minimally invasive alternatives targeting the proximal small bowel to mimic surgical bypass effects, potentially achieving metabolic improvements by direct modulation of nutrient flow and gut hormone regulation independent of weight loss.
Study Design
The ENDO trial was a rigorous multicenter, double-blind, randomized, sham-controlled trial involving 320 participants with poorly controlled T2DM (mean baseline HbA1c ~8.79%) and concomitant obesity (mean BMI ~38.45 kg/m2). Subjects were randomized 2:1 to receive either the EndoBarrier DJBL or a sham endoscopic procedure, alongside standardized medical management and lifestyle counseling. The DJBL is an endoscopically placed 60-cm fluoropolymer liner implanted in the duodenum extending to the jejunum, intended to prevent nutrient contact with the proximal intestinal mucosa. The primary efficacy endpoint was the mean difference in change in HbA1c at 12 months; the primary safety endpoint was the incidence of device-related serious adverse events (SAEs). Secondary endpoints included percentage total weight loss (%TWL) and the proportion of patients reaching glycemic and weight loss targets (HbA1c ≤7%, TWL ≥5%). Data analyses employed a modified intent-to-treat approach.
Key Findings and Results
At 12 months, the DJBL group experienced a substantial decrease in HbA1c (-1.10±1.45%) compared with the sham group (-0.28±1.54%), reaching statistical significance (P=0.0004). This reduction represents a clinically relevant improvement in glycemic control that might translate into reduced diabetes-related complications. Weight loss was also markedly greater in the DJBL arm (7.7±9.6% TWL) relative to sham (2.1±5.4% TWL; P<0.0001), consistent with metabolic benefit beyond glycemic indices.
Notably, a significantly higher proportion of DJBL-treated patients achieved key therapeutic goals: 28.3% attained HbA1c ≤7% compared to 9.4% in the sham group (P<0.0003), and 60.4% achieved at least 5% total weight loss versus 21.3% in sham (P<0.0001). These results support the device's dual impact on glycemic and weight management.
Safety analysis revealed device-related serious adverse events occurred in 9.4% of DJBL patients, including device intolerance (3.7%), gastrointestinal hemorrhage (2.8%), and hepatic abscess (2.3%), prompting early removal of the device in several cases. No deaths were reported, and adverse events resolved with appropriate management. These findings highlight a safety profile requiring patient selection and close monitoring but suggest acceptable risk-benefit balance given the metabolic improvements.
Expert Commentary
The ENDO trial represents a critical advancement in the field of endoscopic metabolic therapies, addressing a population with challenging clinical management. The rigorous sham-controlled design offers robust evidence distinguishing DJBL efficacy from placebo effects and lifestyle modifications alone. Mechanistically, DJBL likely induces hormonal and metabolic changes akin to surgical bypass, including alterations in incretin pathways, bile acid signaling, and gut microbiome interactions, warranting further mechanistic studies.
However, the device’s safety concerns, notably hepatic abscess incidence, mandate careful risk assessment. The relatively high incidence of intolerance suggests that patient comfort and device tolerability remain barriers requiring technological refinements and tailored patient selection criteria.
Additional longer-term follow-up data could clarify durability of metabolic benefits after device removal, as previous observational studies suggest some regression. Future trials might explore combination with pharmacotherapy or alternative endoluminal devices to optimize outcomes. Clinicians should balance individual patient risks and preferences when considering DJBL as adjunctive therapy.
Conclusion
The ENDO trial establishes the EndoBarrier duodenal-jejunal bypass liner as a promising minimally invasive option for improving glycemic control and inducing significant weight loss in poorly controlled T2DM patients with obesity. Though associated with manageable but notable adverse events, the device offers an important alternative for patients in whom surgery is contraindicated or undesirable. Ongoing innovation and long-term evidence will be essential to define its optimal role in integrated metabolic disease management.
Funding and Clinical Trial Registration
The study was supported by the manufacturers of the EndoBarrier device and conducted under rigorous ethical approvals. The trial is registered on ClinicalTrials.gov identifier NCT##### (specific number not provided here).
References
- Thompson CC, Jirapinyo P, McCarty TR, et al. A Multicenter Double-blind Randomized Sham-controlled Trial Assessing the EndoBarrier Duodenal-jejunal Bypass Liner for the Treatment of Poorly Controlled Type 2 Diabetes Mellitus With Concomitant Obesity: The ENDO Trial. Ann Surg. 2025 Nov;284(1):34-42. PMID: 41199626.
- Kedia P, et al. Metabolic effects of duodenal-jejunal bypass liner implantation in patients with obesity and type 2 diabetes: A systematic review and meta-analysis. Gastrointest Endosc. 2022;95(5):945-956.
- Rubino F, et al. Mechanisms of metabolic improvements after bariatric surgery: The role of incretin hormones and intestinal nutrient passage. Nat Rev Endocrinol. 2018;14(3):150-161.
