Effects on Remission of Type 2 Diabetes Mellitus Following Gastric Bypass Alone vs Gastric Bypass Combined With Truncal Vagotomy

Summary

This randomized, triple-blind clinical trial investigates whether adding truncal vagotomy to Roux-en-Y gastric bypass (RYGB) enhances remission of type 2 diabetes mellitus (T2DM) in patients with obesity. The study explores whether modulation of vagal signaling provides superior metabolic outcomes compared to standard RYGB alone.

Background:

RYGB is a proven metabolic procedure capable of inducing diabetes remission; however, the mechanisms remain incompletely defined. Emerging evidence supports a duodenum-centered neurohormonal model suggesting that amplified digestion-driven by vagal and hormonal hyperstimulation-plays a key role in the development of insulin resistance. The vagus nerve regulates pancreatic and biliary secretion, as well as gut hormone release. By combining truncal vagotomy with RYGB, the study aims to attenuate vagal overactivation and evaluate its impact on glucose homeostasis and hormonal adaptation.

Design:

Eligible adults (18-65 years) with BMI ≥30 kg/m² and confirmed T2DM (HbA1c ≥6.5%, or on antidiabetic therapy with HbA1c ≥6.1%) will be randomized to:

1. RYGB alone, or
2. RYGB with truncal vagotomy. Participants, postoperative staff, and assessors will remain blinded to allocation.

Primary Outcome:

Remission of T2DM at 12 months postoperatively, defined as fasting plasma glucose \<100 mg/dL and HbA1c \<6.0% without antidiabetic medication for at least one year.

Secondary Outcomes:

Changes in HbA1c, fasting glucose, insulin, C-peptide, OGTT-derived indices, GLP-1, CCK, PYY, GLP-2, oxyntomodulin responses, HOMA-IR, body composition, cardiovascular risk markers, medication use, and quality-of-life parameters. Surgical metrics include hospital stay, readmissions, complications, gastrointestinal symptoms, nutritional deficiencies, and bone density changes.

Follow-Up:

Assessments occur preoperatively and at 1, 3, 6, and 12 months after surgery.

Significance:

The VagusSx Trial tests whether targeted vagal and duodenal pathway interruption can improve glycemic control beyond weight loss alone, offering a novel, physiology-based strategy for durable diabetes remission.

Conditions

• Diabetes Mellitus Type 2

Interventions

PROCEDURE

Roux-en-Y Gastric Bypass plus Truncal Vagotomy

Laparoscopic Roux-en-Y gastric bypass performed according to protocol, including creation of a small gastric pouch, gastrojejunostomy, and jejunojejunostomy. In addition, bilateral truncal vagotomy is performed at the distal esophagus, dividing both anterior and posterior vagal trunks to reduce vagal stimulation of the gastrointestinal tract. The combined procedure aims to assess whether vagotomy enhances type 2 diabetes mellitus remission beyond the effect of gastric bypass alone.

PROCEDURE

Roux-en-Y Gastric Bypass

Laparoscopic Roux-en-Y gastric bypass performed according to protocol, including creation of a small gastric pouch, gastrojejunostomy, and jejunojejunostomy. No vagotomy is performed. This serves as the active comparator to evaluate the independent effect of adding truncal vagotomy on type 2 diabetes mellitus remission.

Sponsors & Collaborators

• National and Kapodistrian University of Athens

  collaborator OTHER

• University Research Institute for the Study of Genetic & Malignant Disorders in Childhood

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

68 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-24

Primary Completion

2028-12-31

Completion

2028-12-31

Countries

• Greece

Study Locations