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Introduction Proximal intestinal mucosal ablation (PIMA) is an emerging metabolic endoscopic intervention for type 2 diabetes (T2D). It is designed to replicate the glycaemic effects of gastric bypass by targeted ablation of up to 60 cm of post-ampullary small-bowel mucosa using a through-the-scope radiofrequency vapour ablation (RFVA) catheter. Preliminary studies suggest that short segment ablation (10-15 cm) of the duodenal mucosa may permit withdrawal of exogenous insulin when combined with glucagon-like peptide-1 receptor agonists (GLP-1RA) in selected patients. We postulated that extending the ablation length into the proximal small intestine could achieve insulin independence without adjunctive GLP-1RA therapy. Accordingly, this study evaluated the safety and feasibility of PIMA in patients with insulin-requiring T2D.Methods A prospective, single centre study evaluating PIMA using RFVA among patients with IR-T2D on daily long-acting insulin for ≥3 months (total dose ≤0.6 units/kg) and a glycated haemoglobin (HbA1c) ≤8% ( NCT06655740). Patients were enrolled at Clinica Colonia, Santiago, between Sep-2024 to May-2025. After screening, patients started continuous glucose monitoring (CGM) and entered a 4-week run-in to ensure stable control. Post run-in, insulin was stopped, and PIMA performed via an adult colonoscope (Olympus HQ190L) with the RFVA catheter, at a dose of 250J (n=2) or 275J (n=18) with double application, under general anaesthesia. Post-procedure, patients followed a 14-day modified diet, continued oral glucose-lowering agents (GLA), and received standard lifestyle advice for T2D. Primary outcomes were serious adverse events (SAEs) and the proportion of patients free of insulin with a HbA1c ≤7.5% at 6-months.Results In total, 20 patients (average age 50.5 years [IQR 43-52], 60% female) underwent PIMA. The average duration of T2D was 4.5 years (IQR 3-7), baseline HbA1c 7.1% (SD 1.0), BMI 33.0 kg/m 2 (SD 5.2), average oral GLA use 1 (IQR 1-2), and baseline insulin dose 27 units (SD 9.6). PIMA was successful in all patients with an average treatment length of 60 cm (IQR 60-65) and 48.3 (SD 7.7) ablations. The average procedure time was 58.3 minutes (SD 15.0) and catheter time 41.5 minutes (SD 25.5). Follow-up enteroscopy and biopsy was normal in all cases. There were no SAEs or clinically significant hypoglycaemia. At 6-months, 100% (n=19) remained off exogenous insulin without need for concomitant GLP-1RA, and 84.2% (n=16) maintained a HbA1c ≤7.5%. Oral GLAs were increased in three patients and one patient dropped out at 3-months who was off insulin with a HbA1c of 6.4%. Over follow-up, the average BMI decreased at both 3- and 6-months by 2.6 kg/m2 (SD 1.9; p<0.001) and 2.7 kg/m2 (SD 2.1; p<0.001), respectively.Conclusions PIMA was safe and enabled discontinuation of exogenous insulin in all participants, with 84% maintaining insulin independence without escalation of oral pharmacotherapy.