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

OBJECTIVE: An endoscopically placed duodenal-jejunal bypass liner (DJBL) may provide a safe adjunctive therapy for those with poorly controlled type 2 diabetes mellitus (T2DM) and obesity.

BACKGROUND: Although some endoscopic therapies have been shown to improve glycemic indices secondary to weight loss, small bowel interventions may have direct metabolic effects. A meta-analysis of observational studies demonstrated reduction in HbA1c by 1.3% at 1 year after DJBL in patients with T2DM and obesity.

METHODS: This was a multicenter, double-blind, randomized, sham-controlled trial comparing DJBL to sham procedure with medical management and lifestyle modification. Primary endpoints included mean difference in changes in HbA1c at 12 months between arms, and device-related serious adverse events (SAEs). Secondary endpoints included percent total weight loss (%TWL) and subjects achieving HbA1c≤7% and TWL≥5% at 12 months.

RESULTS: Three hundred twenty subjects were randomized to DJBL (n=212) and sham (n=108). Baseline HbA1c and BMI were 8.79±0.92% and 38.45±5.75 kg/m 2 . On modified intent-to-treat analysis, change in HbA1c at 12 months was -1.10±1.45% and -0.28±1.54% for DJBL and sham groups, respectively ( P =0.0004). Rate of device-related SAEs was 9.4% including intolerance (3.7%), hemorrhage (2.8%), and hepatic abscess (2.3% stopping study early). At 12 months, DJBL group experienced greater weight loss compared with sham (7.7±9.6% TWL and 2.1±5.4% TWL, respectively; P <0.0001), with significantly more patients achieving HbA1c ≤ 7% (28.3% vs. 9.4%; P <0.0003) and TWL ≥ 5% (60.4% vs. 21.3%; P <0.0001).

CONCLUSIONS: DJBL met primary glycemic control efficacy and primary safety endpoints, while providing clinically significant weight loss, and comorbidity improvement.