BACKGROUND: Diabetes mellitus (DM) significantly impacts global health and economies. Despite various therapies, managing DM remains challenging. Bariatric surgery has shown efficacy in obese patients with type 2 diabetes mellitus (T2DM), but its utilization remains low. Innovative, less invasive endoscopic approaches such as duodenal mucosal resurfacing show potential in treating T2DM. This article presents the results of a First in Human (FIH) study using a duodenal submucosal laser ablation investigational device for T2DM treatment. METHODS: A prospective, single-arm, open-label study evaluated the safety and efficacy of the Digma System Endoscopic procedure for duodenal submucosal laser ablation in consecutive enrolled T2DM patients. RESULTS: The study was conducted from July 2017 to December 2020 and enrolled 31 patients for the Digma System Endoscopic procedure. The Dose Escalation Cohort (DEC) used sub-therapeutic laser doses for training and safety. The Treatment Cohort (TC) of 25 patients received therapeutic doses, resulting in HbA1c reductions of -0.6% at 6 months (p = 0.014) and -0.4% at 12 months (p = 0.062). Fasting glucose dropped 17.3 mg/dL (p = 0.173) at 6 months and 28 mg/dL (p = 0.022) at 12 months. Post-prandial glucose improvements were also observed. HOMA-IR improved at 3 and 6 months. PAGI-SYM and PAGI-QOL showed stable to slightly improved GI symptoms and quality of life. Two severe adverse events were unrelated to the procedure. CONCLUSION: The study demonstrates the safety, feasibility, and potential efficacy of the Digma System Endoscopic procedure. Evidence suggests improvements in HbA1c, fasting and post-prandial glucose, and HOMA-IR levels could be attributed to the Digma System Endoscopic procedure.

Department of Diabetes Diabetes Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Gastroenterology Hepatology and Pancreatology Internal and Cardiologic Clinic University Hospital Ostrava Ostrava Czech Republic

Department of Hepatogastroenterology Transplantation Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Internal Medicine 2nd Faculty of Medicine Charles University Prague Czech Republic

Digma Medical Givat Shmuel Israel

Endocrinology and Metabolism Shaare Zedek Medical Center Jerusalem Israel

Experimental Medicine Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics of the General University Hospital and of the 1st Faculty of Medicine of Charles University Prague Czech Republic

Shaare Zedek Medical Center Digestive Disease Institute Jerusalem Israel

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