Proximal intestinal mucosal ablation (PIMA) is a novel metabolic endoscopic procedure under investigation for the treatment of patients with type 2 diabetes (T2D). The aim is to replicate the metabolic benefits of gastric bypass surgery by ablating up to 60 cm of abnormal post-ampullary intestinal mucosa using a through-the-scope radiofrequency vapor ablation (RFVA) catheter. Early pilot data suggests that endoscopic ablation of 10-15 cm of duodenal mucosa could eliminate the need for exogenous insulin therapy in T2D when combined with glucagon-like peptide-1 receptor agonists (GLP-1RA). By extending the length of ablation into the proximal small intestine, we hypothesised that insulin independence could be achieved in patients with insulin-requiring (IR)-T2D without the need for concomitant GLP-1RA therapy. Therefore, we aimed to evaluate the safety and feasibility of PIMA as a treatment for IR-T2D.

A prospective, single-centre study evaluating PIMA using RFVA among patients with IR-T2D on daily long-acting insulin for ≥3 months (≤20% dose alteration within the last month and total dose ≤0.6 units/kg) and a glycated haemoglobin (HbA1c) ≤8% (NCT06655740). Patients were enrolled at Clinica Colonial, 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 was performed via an adult colonoscope (Olympus HQ190L) with the circumferential through-the-scope mesh-tip RFVA catheter under general anaesthesia. RFVA was delivered at a dose of 250-275J with double application to the post-ampullary intestinal mucosa. Post-procedure, patients followed a 14-day modified diet, continued oral glucose-lowering agents (GLA) only, and received standard lifestyle advice for T2D. Primary outcomes were the number of serious adverse events (SAEs), unanticipated adverse device effects (UADEs), and the proportion of patients free of insulin, without need for concomitant GLP-1RA, who had a HbA1c ≤7.5% at 6-months. Secondary exploratory outcomes were change in body mass index (BMI), HbA1c, and time-in-range.

In total, 20 patients with IR-T2D (average age 50.5 years [IQR 43-52], 60% female) underwent PIMA. The average disease duration of T2D was 4.5 years (IQR 3-7), baseline HbA1c was 7.1% (SD 1.0), BMI was 33.0 kg/m2 (SD 5.2), average number of oral GLAs 1 (IQR 1-2), and baseline daily insulin dose 27 units (SD 9.6). PIMA was successful in all patients with an average length of treated bowel of 60 cm (IQR 60-65) and 48.3 (SD 7.7) ablations. Average procedure time was 58.3 minutes (SD 15.0), catheter time 41.5 minutes (SD 25.5), and the majority were treated at 275 J (n=18). Follow-up enteroscopy with biopsy was normal in all patients. There were no SAEs or UADEs, and although asymptomatic sensor readings <3.9 mmol/L occurred, no clinically significant hypoglycaemia was confirmed by symptoms or finger-stick capillary glucose. At 6-months, 100% of patients remained off exogenous insulin (n=19) without need for concomitant GLP-1RA, and 84.2% (n=16) maintained a HbA1c ≤7.5%. One patient withdrew at 3-months while still off insulin with a HbA1c of 6.4%. Three patients with worsening control had oral GLA optimised with use of sodium–glucose co-transporter 2 inhibitor (n=2) or dipeptidyl peptidase-4 inhibitor (n=1). Mean time in range (3.9-10.0 mmol/L) at 3- and 6-months was 91.6% (SD 9.8) and 85.7% (SD 13.5), respectively, with corresponding falls in HbA1c by -0.8% (SD 1.0; p<0.01) and -0.6% (SD 1.0; P<0.05). BMI reduced significantly at 3-months (-2.6 [SD1.9]; p<0.001) and 6-months (-2.7 [SD 2.1]; p<0.001) due to withdrawal of insulin.

Among patients with IR-T2D, PIMA safely enabled discontinuation of insulin in all patients, with 84% maintaining independence without additional medications alongside improved glycaemic control and weight reduction.