Cutting the gatekeeper: unlocking the stomach in diabetic gastroparesis
Aims: To evaluate the efficacy of gastric peroral endoscopic pyloromyotomy (G-POEM) in people with diabetic gastroparesis, focusing on gastric emptying, gastrointestinal symptoms, pyloric function, and glycemic control.
Methods: In this randomized, double-blinded, sham-controlled trial, 20 people with diabetes (10 with type 1 and 10 with type 2 diabetes) and confirmed gastroparesis (gastric retention >10% at 4 hours after a mixed-meal test and a gastroparesis cardinal symptom index [GCSI] score ≥1.9) were included. Participants were randomized to either G-POEM or sham intervention. The primary outcome was change in gastric emptying scintigraphy (GES) at 4 hours. Secondary outcomes included GCSI score, pyloric distensibility index (DI) assessed by EndoFLIP, and HbA1c. Follow-up was conducted over 3 months.
Results: Eighteen participants completed follow-up with one treatment-associated serious adverse event in the G-POEM group and one treatment-unrelated death in the sham group. G-POEM significantly improved gastric emptying, with median GES retention decreasing from 24% to 8% (P=0.021), whereas no change was observed in the sham group (35% vs 33%, P=0.91). The between-group difference in GES change was significant (P=0.045), with complete remission achieved in 66.7% vs 11.1% (P=0.016). Gastrointestinal symptoms improved markedly after G-POEM, with GCSI scores decreasing from 2.35 to 0.75 (P<0.001), while no improvement was observed in the sham group. All G-POEM participants achieved a clinically meaningful (>1-point) improvement in GCSI scores, and 89% had ≥50% symptom reduction with only one patient showing no improvement. Pyloric DI increased significantly in the G-POEM group (4.40 to 6.45 mm²/mm Hg; P=0.009) but not in the sham group, with a significant between-group difference (P<0.001). Symptom improvement correlated with both improved gastric emptying (ρ=0.40, P=0.018) and increased pyloric DI (ρ=−0.39, P=0.032). No significant changes in HbA1c were observed in either group.
Conclusions: G-POEM significantly improved gastric emptying, gastrointestinal symptoms, and pyloric distensibility in people with diabetic gastroparesis. These findings support pyloric dysfunction as a key therapeutic target and highlight G-POEM as a potential treatment option.
Comments: This study provides important evidence in a field where effective treatments for diabetic gastroparesis remain limited and largely symptom driven. By demonstrating improvements in both gastric emptying and symptoms alongside changes in pyloric distensibility, the findings strengthen the concept of pyloric dysfunction as a key therapeutic target and offer a more mechanistic rationale for intervention with G-POEM rather than purely symptomatic management. A major strength of the study is its rigorous methodology, including a prospective, randomized, double-blinded, sham-controlled design, combined with gastric emptying scintigraphy as the primary endpoint. The use of scintigraphy as a gold standard objective and reproducible measure reduces susceptibility to placebo effects and is particularly valuable given the known weak correlation between symptoms and gastric emptying. However, several limitations should be considered including the relatively short follow-up time, which does not allow conclusions regarding its long-term effect. In addition, the small sample size further limits generalizability and induces risk of bias. Overall, the study provides strong early evidence supporting G-POEM as an effective and mechanistically targeted treatment for diabetic gastroparesis, while highlighting the need for larger and longer-term studies to confirm durability and refine patient selection.
Johan Røikjer
Reference. Hansen MS, Miliam PB, Damgaard M, Gögenur I, Hansen CS, Karstensen JG; Diabetic Gastroparesis Collaborative Investigators. Gastric Peroral Endoscopic Pyloromyotomy (G-POEM) Is Effective in the Treatment of Diabetic Gastroparesis: A Randomized, Double-Blinded, Sham-Controlled Trial. Gastroenterology. 2026 Mar 6:S0016-5085(25)06620-X. doi: 10.1053/j.gastro.2025.12.009. Epub ahead of print. PMID: 41790073.
