OBJECTIVE To assess procedural safety and glycemic indices at 6 months in a first-in-human study of duodenal mucosal resurfacing (DMR), a novel, minimally invasive, upper endoscopic procedure involving hydrothermal ablation of the duodenal mucosa, in patients with type 2 diabetes and HbA1c ≥7.5% (58 mmol/mol) on one or more oral antidiabetic agents. RESEARCH DESIGN AND METHODS Using novel balloon catheters, DMR was conducted on varying lengths of duodenum in anesthetized patients at a single medical center. RESULTS A total of 39 patients with type 2 diabetes (screening HbA1c 9.5% [80 mmol/mol]; BMI 31 kg/m2) were treated and included in the interimefficacy analysis: 28 had a long duodenal segment ablated (LS; ∼9.3 cm treated) and 11 had a short segment ablated (SS; ∼3.4 cm treated). Overall, DMR was well tolerated with minimal gastrointestinal symptoms postprocedure. Three patients experienced duodenal stenosis treated successfully by balloon dilation. HbA1c was reduced by 1.2% at 6 months in the full cohort (P < 0.001). More potent glycemic effects were observed among the LS cohort, who experienced a 2.5% reduction in mean HbA1c at 3months postprocedure vs. 1.2%in the SS group (P < 0.05) and a 1.4% reduction at 6 months vs. 0.7% in the SS group (P = 0.3). This occurred despite net medication reductions in the LS cohort between 0 and 6 months. Among LS patients with a screening HbA1c of 7.5-10% (58-86 mmol/mol) and on stable antidiabetic medications postprocedure, HbA1c was reduced by 1.8% at 6 months (P < 0.01). CONCLUSIONS Single-procedure DMR elicits a clinically significant improvement in hyperglycemia in patients with type 2 diabetes in the short-term, with acceptable safety and tolerability. Long-termsafety, efficacy, and durability and possiblemechanisms of action require further investigation.

Rajagopalan, H., Cherrington, A. D., Thompson, C. C., Kaplan, L. M., Rubino, F., Mingrone, G., Becerra, P., Rodriguez, P., Vignolo, P., Caplan, J., Rodriguez, L., Galvao Neto, M. P., 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>>, 2016; 39 (12): 2254-2261. [doi:10.2337/dc16-0383] [http://hdl.handle.net/10807/93099]

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes: 6-month interim analysis from the first-in-human proof-of-concept study

Lee M.; Rubino;Francesco; Mingrone;
2016

Abstract

OBJECTIVE To assess procedural safety and glycemic indices at 6 months in a first-in-human study of duodenal mucosal resurfacing (DMR), a novel, minimally invasive, upper endoscopic procedure involving hydrothermal ablation of the duodenal mucosa, in patients with type 2 diabetes and HbA1c ≥7.5% (58 mmol/mol) on one or more oral antidiabetic agents. RESEARCH DESIGN AND METHODS Using novel balloon catheters, DMR was conducted on varying lengths of duodenum in anesthetized patients at a single medical center. RESULTS A total of 39 patients with type 2 diabetes (screening HbA1c 9.5% [80 mmol/mol]; BMI 31 kg/m2) were treated and included in the interimefficacy analysis: 28 had a long duodenal segment ablated (LS; ∼9.3 cm treated) and 11 had a short segment ablated (SS; ∼3.4 cm treated). Overall, DMR was well tolerated with minimal gastrointestinal symptoms postprocedure. Three patients experienced duodenal stenosis treated successfully by balloon dilation. HbA1c was reduced by 1.2% at 6 months in the full cohort (P < 0.001). More potent glycemic effects were observed among the LS cohort, who experienced a 2.5% reduction in mean HbA1c at 3months postprocedure vs. 1.2%in the SS group (P < 0.05) and a 1.4% reduction at 6 months vs. 0.7% in the SS group (P = 0.3). This occurred despite net medication reductions in the LS cohort between 0 and 6 months. Among LS patients with a screening HbA1c of 7.5-10% (58-86 mmol/mol) and on stable antidiabetic medications postprocedure, HbA1c was reduced by 1.8% at 6 months (P < 0.01). CONCLUSIONS Single-procedure DMR elicits a clinically significant improvement in hyperglycemia in patients with type 2 diabetes in the short-term, with acceptable safety and tolerability. Long-termsafety, efficacy, and durability and possiblemechanisms of action require further investigation.
Inglese
Rajagopalan, H., Cherrington, A. D., Thompson, C. C., Kaplan, L. M., Rubino, F., Mingrone, G., Becerra, P., Rodriguez, P., Vignolo, P., Caplan, J., Rodriguez, L., Galvao Neto, M. P., 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>>, 2016; 39 (12): 2254-2261. [doi:10.2337/dc16-0383] [http://hdl.handle.net/10807/93099]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/93099
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