taVNS Adjunctive to Tirzepatide Explored for Suboptimal Weight Loss in Overweight/Obese Patients

Many individuals struggle with obesity and overweight, conditions linked to numerous chronic diseases. While novel incretin receptor agonists like tirzepatide have revolutionized weight management, a significant subset of patients exhibits a suboptimal response, failing to achieve clinically meaningful weight loss. This creates a critical unmet need for adjunctive therapies that can enhance metabolic outcomes. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique targeting the vagus nerve, which plays a crucial role in regulating gastrointestinal function, satiety, and metabolism. Its potential to modulate neural pathways involved in appetite control and energy expenditure makes it a promising candidate to augment the effects of incretin-based therapies.

This single-center, randomized, participant-blinded, sham-controlled pilot trial will enroll 24 overweight or obese participants who show a suboptimal weight-loss response to incretin receptor agonist therapy. Participants will be randomly assigned to receive either taVNS plus tirzepatide 5 mg or sham stimulation plus tirzepatide 5 mg. The intervention will last for 12 weeks. The primary objective is to compare the percent change in body weight from baseline to week 12 between the two groups, aiming to evaluate the adjunctive effect of taVNS.

This is a pilot trial protocol, and therefore no findings are available yet. The study aims to determine if taVNS significantly enhances weight loss when added to tirzepatide therapy in patients who have previously shown a suboptimal response to incretin receptor agonists.