METABOLIC OUTCOMES AND MECHANISMS OF ACTION FOR DUODENAL BI-PARTITION IN THE TREATMENT OF OBESITY AND TYPE 2 DIABETES MELLITUS: A 4-YEAR PROSPECTIVE OBSERVATIONAL STUDY

Introduction: Roux-en-Y gastric bypass (RYGB) is an effective treatment for patients suffering from obesity and concomitant type 2 diabetes mellitus (T2DM). Nevertheless, less than 2% of eligible patients choose to undergo the surgery. More recently, a hybrid endoscopic approach using self-forming magnets (SFMs) (GI Windows, Westwood, MA) to create a duodenal bi-partition, partially mimicking the function of RYGB, has been developed. This study aims to assess safety, efficacy, and durability as well as the mechanisms of action for this novel procedure.

Methods: This was a prospective observational study. Inclusion criteria were obesity with concomitant T2DM. Exclusion criteria were poorly controlled T2DM, defined as hemoglobin A1c (HbA1c) >10% and insulin use. Subjects underwent the endoscopic enteral diversion procedure (Sutureless Neodymium Anastomosis Procedure [SNAP]) where SFMs were deployed endoscopically at the duodenal bulb and laparoscopically in the ileum. All subjects underwent a mixed meal tolerance test at months 0, 1 and 12 for gut hormone measurement. Part I: Efficacy of SNAP up to 4 years was assessed and reported using the changes in HbA1c and percent total weight loss (%TWL). Part II: Changes in gut hormones, including ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and bile acids, at 1 and 12 months were assessed. Additionally, predictors of response, defined as a decrease in HbA1c by ≥1% at 12 months, were evaluated.

Results: A total of 14 subjects were enrolled in the study. Baseline age and BMI were 48±9 years and 40.4±3.7 kg/m². Part I: At 12, 24, 36 and 48 months, hemoglobin A1c decreased from 8.3±1.3% to 6.4±0.6%, 6.6±1.2%, 6.4±1.5% and 6.9±1.8%, respectively (p<0.05 compared to baseline for all). At 12, 24, 36 and 48 months, the amount of weight loss was 13.4±8.6%, 14.2±11.5%, 15.6±13.6% and 13.5±12.9% TWL, respectively (p<0.0005 compared to baseline for all) (Figure 1). Part II: At 12 months, postprandial GLP-1, PYY, and bile acids, and fasting ghrelin significantly increased (Figure 2). The amount of change in postprandial GLP-1 and PYY at 1 month was significantly higher in the responder group compared to the non-responder group (GLP-1: +198.4±168.4 pg/mL versus -143.7±73.7 pg/mL, p=0.04; PYY: +3806.3±3274.0 pg/mL versus -3692.7±2009.6 pg/mL, p=0.007) (Figure 2).

Conclusion: SNAP appears safe and effective at treating obesity and concomitant T2DM, with durability lasting up to at least 4 years. The mechanisms of action of these metabolic improvements are likely multifactorial including changes in gut hormones.