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

Zobrazit více v PubMed

International Diabetes Federation , IDF Diabetes Atlas. 10th ed., (2022), https://diabetesatlas.org/.

Zheng Y., Ley S. H., and Hu F. B., “Global Aetiology and Epidemiology of Type 2 Diabetes Mellitus and its Complications,” Nature Reviews Endocrinology 14, no. 2 (2018): 88–98, 10.1038/nrendo.2017.151. PubMed DOI

Wadden T. A., West D. S., Delahanty L., et al., “The Look AHEAD Study: A Description of the Lifestyle Intervention and the Evidence Supporting it,” Obesity 14, no. 5 (2006): 737–752, 10.1038/oby.2006.84. PubMed DOI PMC

Nauck M. A., Wefers J., and Meier J. J., “Treatment of Type 2 Diabetes: Challenges, Hopes, and Anticipated Successes,” Lancet Diabetes & Endocrinology 9, no. 8 (2021): 525–544, 10.1016/s2213-8587(21)00113-3. PubMed DOI

Davies M. J., Aroda V. R., Collins B. S., et al., “Management of Hyperglycaemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD),” Diabetologia 65, no. 12 (2022): 1925–1966, 10.1007/s00125-022-05787-2. PubMed DOI PMC

American Diabetes Association Professional Practice Committee “6. Glycemic Targets: Standards of Medical Care in Diabetes‐2022,” Diabetes Care 45, no. Suppl 1 (2022): S83–S96, 10.2337/dc22-s006. PubMed DOI

Le P., Ayers G., Misra‐Hebert A. D., et al., “Adherence to the American Diabetes Association’s Glycemic Goals in the Treatment of Diabetes Among Older Americans, 2001–2018,” Diabetes Care 45, no. 5 (2022): 1107–1115, 10.2337/dc21-1507. PubMed DOI

American Diabetes A., “12. Older Adults: Standards of Medical Care in Diabetes‐2021,” Diabetes Care 44, no. Suppl 1 (2021): S168–S179, 10.2337/dc21-s012. PubMed DOI

Blasi C., “The Role of the Vagal Nucleus Tractus Solitarius in the Therapeutic Effects of Obesity Surgery and Other Interventional Therapies on Type 2 Diabetes,” Obesity Surgery 26, no. 12 (2016): 3045–3057, 10.1007/s11695-016-2419-2. PubMed DOI

Hsu C.‐C., Almulaifi A., Chen J.‐C., et al., “Effect of Bariatric Surgery vs Medical Treatment on Type 2 Diabetes in Patients With Body Mass Index Lower Than 35: Five‐Year Outcomes,” JAMA surgery 150, no. 12 (2015): 1117–1124, 10.1001/jamasurg.2015.2602. PubMed DOI

Mingrone G., Panunzi S., De Gaetano A., et al., “Bariatric–Metabolic Surgery versus Conventional Medical Treatment in Obese Patients With Type 2 Diabetes: 5 Year Follow‐Up of an Open‐Label, Single‐Centre, Randomised Controlled Trial,” Lancet 386, no. 9997 (2015): 964–973, 10.1016/s0140-6736(15)00075-6. PubMed DOI

van Baar A. C. G., Nieuwdorp M., Holleman F., Soeters M. R., Groen A. K., and Bergman J., “The Duodenum Harbors a Broad Untapped Therapeutic Potential,” Gastroenterology 154, no. 4 (2018): 773–777, 10.1053/j.gastro.2018.02.010. PubMed DOI

Dixon J. B., le Roux C. W., Rubino F., and Zimmet P., “Bariatric Surgery for Type 2 Diabetes,” Lancet 379, no. 9833 (2012): 2300–2311, 10.1016/s0140-6736(12)60401-2. PubMed DOI

Rubino F., Forgione A., Cummings D. E., et al., “The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes,” Annals of Surgery 244, no. 5 (2006): 741–749, 10.1097/01.sla.0000224726.61448.1b. PubMed DOI PMC

Kirwan J. P., Courcoulas A. P., Cummings D. E., et al., “Diabetes Remission in the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS‐T2d),” Diabetes Care 45, no. 7 (2022): 1574–1583, 10.2337/dc21-2441. PubMed DOI PMC

Punchai S., Wilson R. L., Meister K. M., et al., “Does Colectomy Improve Type 2 Diabetes?.” Obesity Surgery 30, no. 6 (2020): 2429–2433, 10.1007/s11695-019-04346-w. PubMed DOI

Frattini F., Borroni G., Lavazza M., et al., “New Endoscopic Procedures for Diabetes Mellitus Type 2 and Obesity Treatment,” Gland Surgery 5, no. 5 (2016): 458–464, 10.21037/gs.2016.10.03. PubMed DOI PMC

van Baar A. C. G., Holleman F., Crenier L., et al., “Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes Mellitus: One Year Results From the First International, Open‐Label, Prospective, Multicentre Study,” Gut 69, no. 2 (2020): 295–303, 10.1136/gutjnl-2019-318349. PubMed DOI PMC

Mingrone G., van Baar A. C. G., Deviere J., et al., “Safety and Efficacy of Hydrothermal Duodenal Mucosal Resurfacing in Patients With Type 2 Diabetes: The Randomised, Double‐Blind, Sham‐Controlled, Multicentre REVITA‐2 Feasibility Trial,” Gut 71, no. 2 (2022): 254–264, 10.1136/gutjnl-2020-323608. PubMed DOI PMC

Rajagopalan H., Cherrington A. D., Thompson C. C., et al., “Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes: 6‐Month Interim Analysis From the First‐In‐Human Proof‐Of‐Concept Study,” Diabetes Care 39, no. 12 (2016): 2254–2261, 10.2337/dc16-0383. PubMed DOI

Busch C. B. E., Meiring S., van Baar A. C. G., Holleman F., Nieuwdorp M., and Bergman J. J. G. H. M., “Recellularization via Electroporation Therapy of the Duodenum Combined With Glucagon‐Like Peptide‐1 Receptor Agonist to Replace Insulin Therapy in Patients With Type 2 Diabetes: 12‐month Results of a First‐in‐Human Study,” Gastrointestinal Endoscopy 100, no. 5 (2024): 896–904, 10.1016/j.gie.2024.04.2904. PubMed DOI

McCarty T. R. and Thompson C. C., “Bariatric and Metabolic Therapies Targeting the Small Intestine,” Techniques and Innovations in Gastrointestinal Endoscopy 22, no. 3 (2020): 145–153, 10.1016/j.tige.2020.03.008. PubMed DOI PMC

Rodriguez‐Grunert L., Galvao Neto M. P., Alamo M., Ramos A. C., Baez P. B., and Tarnoff M., “First Human Experience With Endoscopically Delivered and Retrieved Duodenal‐Jejunal Bypass Sleeve,” Surgery for Obesity and Related Diseases: Official Journal of the American Society for Bariatric Surgery 4, no. 1 (2008): 55–59, 10.1016/j.soard.2007.07.012. PubMed DOI

Koehestanie P., de Jonge C., Berends F. J., Janssen I. M., Bouvy N. D., and Greve J. W., “The Effect of the Endoscopic Duodenal‐Jejunal Bypass Liner on Obesity and Type 2 Diabetes Mellitus, a Multicenter Randomized Controlled Trial,” Annals of Surgery 260, no. 6 (2014): 984–992, 10.1097/sla.0000000000000794. PubMed DOI

Matthews D. R., Hosker J. P., Rudenski A. S., Naylor B. A., Treacher D. F., and Turner R. C., “Homeostasis Model Assessment: Insulin Resistance and Beta‐Cell Function From Fasting Plasma Glucose and Insulin Concentrations in Man,” Diabetologia 28, no. 7 (1985): 412–419, 10.1007/bf00280883. PubMed DOI

Cherrington A. D., Rajagopalan H., Maggs D., and Devière J., “Hydrothermal Duodenal Mucosal Resurfacing: Role in the Treatment of Metabolic Disease,” Gastrointestinal Endoscopy Clinics of North America 27, no. 2 (2017): 299–311, 10.1016/j.giec.2016.12.002. PubMed DOI

Nanna M. G., Kolkailah A. A., Page C., Peterson E. D., and Navar A. M., “Use of Sodium‐Glucose Cotransporter 2 Inhibitors and Glucagonlike Peptide‐1 Receptor Agonists in Patients With Diabetes and Cardiovascular Disease in Community Practice,” JAMA Cardiol 8, no. 1 (2023): 89–95, 10.1001/jamacardio.2022.3839. PubMed DOI PMC

Jain P., Hejjaji V., Thomas M. B., et al., “Use of Primary Bariatric Surgery Among Patients With Obesity and Diabetes. Insights From the Diabetes Collaborative Registry,” International Journal of Obesity 46, no. 12 (2022): 2163–2167, 10.1038/s41366-022-01217-w. PubMed DOI

Cefalu W. T., Rubino F., and Cummings D. E., “Metabolic Surgery for Type 2 Diabetes: Changing the Landscape of Diabetes Care,” Diabetes Care 39, no. 6 (2016): 857–860, 10.2337/dc16-0686. PubMed DOI PMC

Nudel J. and Sanchez V. M., “Surgical Management of Obesity,” Metabolism—Clinical and Experimental 92 (2019): 206–216, 10.1016/j.metabol.2018.12.002. PubMed DOI

Rajagopalan H., Lopez‐Talavera J. C., Klonoff D. C., and Cherrington A. D., “A Gut‐Centric Model of Metabolic Homeostasis,” Journal of Diabetes Science and Technology 16, no. 6 (2022): 1567–1574, 10.1177/19322968211044523. PubMed DOI PMC

Committee A. SoP., Ben‐Menachem T., Decker G. A., et al., “Adverse Events of Upper GI Endoscopy,” Gastrointestinal Endoscopy 76, no. 4 (2012): 707–718, 10.1016/j.gie.2012.03.252. PubMed DOI

Furness J. B., Rivera L. R., Cho H. J., Bravo D. M., and Callaghan B., “The Gut as a Sensory Organ,” Nature Reviews Gastroenterology & Hepatology 10, no. 12 (2013): 729–740, 10.1038/nrgastro.2013.180. PubMed DOI

Mayer E. A., “Gut Feelings: The Emerging Biology of Gut‐Brain Communication,” Nature Reviews Neuroscience 12, no. 8 (2011): 453–466, 10.1038/nrn3071. PubMed DOI PMC