Impact of Neuropathy on the Risk of Semaglutide-Induced Gastric Retention

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert their effects by mimicking the action of endogenous GLP-1, activating GLP-1 receptors located in the pancreas, brain, and gastrointestinal tract. On one hand, they promote insulin secretion and suppress glucagon release; on the other, they reduce gastrointestinal motility and delay gastric emptying by stimulating the sympathetic nervous system and inhibiting the parasympathetic nervous system, including enhancing pyloric sphincter contraction. Through these dual mechanisms, GLP-1RAs improve glycemic control and facilitate weight management in patients with type 2 diabetes mellitus (T2DM).

Multiple prior studies and recent meta-analyses have shown that continuous use of GLP-1RAs increases the risk of gastric retention, potentially leading to aspiration and significantly elevating anesthesia-related risk. As a result, several recent expert consensus statements and clinical guidelines-including the 2023 ASA Expert Consensus and the 2025 ASGE Clinical Guidelines-recommend that weekly GLP-1RAs be discontinued for at least one week prior to procedures requiring anesthesia, regardless of dosage. For patients whose discontinuation interval is less than one week, preoperative gastric ultrasound is advised to rule out gastric retention; otherwise, anesthesia should proceed under a "full stomach" protocol.

Given the close connection between GLP-1RA pharmacodynamics and both the autonomic and peripheral nervous systems-and considering that neuropathy is one of the most prevalent complications in T2DM patients-a previous study explored the role of diabetic neuropathy in GLP-1RA-induced delayed gastric emptying. Interestingly, it found that GLP-1RA use in diabetic patients with neuropathy did not significantly slow gastric emptying. However, this study was limited by a small sample size and did not evaluate the actual risk of gastric retention, limiting its clinical relevance.

To further investigate the impact of neuropathy on GLP-1RA-induced gastric retention, we propose a single-center, prospective, observational study. Semaglutide, the most widely used weekly GLP-1RA, will be selected as the study drug. The study will enroll T2DM patients with or without diabetic neuropathy who have been on long-term semaglutide therapy (≥4 weeks) prior to undergoing upper endoscopy. The primary objective is to assess the risk of gastric retention under endoscopic examination.

The findings of this study may contribute to more personalized perioperative management strategies for diabetic patients on semaglutide, potentially reducing anesthesia-related risks while minimizing the glycemic instability associated with prolonged drug discontinuation.

Inclusion criteria

• Confirmed diagnosis of diabetes mellitus.
• Long-term use of semaglutide (for at least 4 weeks) without discontinuation prior to endoscopic examination.
• Age ≥ 18 years, with no restriction on sex.
• American Society of Anesthesiologists (ASA) physical status classification I-II.
• Fasting for at least 8 hours and no water intake for at least 4 hours prior to gastroscopy.
• Underwent assessment for both autonomic and peripheral neuropathy within 2 weeks prior to gastroscopy, with a clear determination of neuropathy status.

Exclusion criteria

• History of hiatal hernia or any prior gastric surgery (including gastrectomy, Roux-en-Y gastric bypass, etc.).
• Pregnancy.
• Medically unfit for gastrointestinal endoscopy.
• Deemed unsuitable for participation at the discretion of the investigators.