Proximal Intestinal Mucosal Ablation (PIMA) is an emerging endoscopic therapy for type 2 diabetes that may improve glycaemia and enable discontinuation of exogenous insulin use. Given the burden and adverse effects of long-term insulin therapy, reducing or eliminating its use could yield meaningful economic benefits. We aimed to develop a cost-effectiveness model, from a UK National Health Service (NHS) perspective, to evaluate PIMA compared with standard-of-care (SoC; continued insulin therapy), as well as its cost impact relative to escalation to the glucagon-like peptide-1 receptor agonist (GLP-1RA) Semaglutide.

A Markov model compared PIMA to SoC and GLP-1RA escalation over 2- and 5-year horizons. Three health states (OFF-insulin, ON-insulin, death) were modelled using 6-month cycles and 3% annual discounting. PIMA was assumed to achieve complete insulin discontinuation, followed by time-varying relapse back to insulin based on current data. Relapse was estimated as a gradual increment from 0-45% (sensitivity analysis up to 68%) over 5-years with increases in oral medication by 50%. GLP-1RA therapy was modelled using UK acquisition costs (£294/month) and real-world discontinuation and insulin-reduction effects. Outcomes included costs, QALYs, incremental costs, incremental QALYs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was evaluated using one-way, scenario, and probabilistic sensitivity analyses (PSA), varying PIMA price, relapse probability, escalation rates, and utilities, with a £30,000/QALY willingness-to-pay (WTP) threshold.

Over 2 years, PIMA yielded QALY gains of 0.16-0.19 at incremental costs of £3,500-3,700, producing ICERs of £18,000-23,500/QALY at the base-case device cost (£8,000), within the National Institute for Health and Care Excellence (NICE) £20,000–30,000/QALY threshold. Over 5 years, QALY gains were smaller (0.10-0.12) and incremental costs remained substantial (£4,700-5,100), resulting in ICERs of £41,700-49,000/QALY. PSA generated a mean ICER of £31,018/QALY, with 60–65% probability of cost-effectiveness at £30,000/QALY. Under favourable assumptions, ICERs ranged from £18,700-32,800/QALY and under unfavourable assumptions, £23,400-50,300/QALY. At base cost, ICER was most sensitive to device cost, followed by relapse reduction and escalation to oral medication. PIMA was consistently dominant relative to Semaglutide, which incurred higher costs and generated lower QALYs across all scenarios. Across all device price modelled (£5,000-15,000), PIMA remained cost-saving compared with Semaglutide, which remained consistent when modelling drug cost variation (±30%).

PIMA is likely cost-effective over a 2-year horizon as an endoscopic treatment for insulin-requiring type 2 diabetes and demonstrates marginal cost-effectiveness over 5 years at current pricing. PIMA is consistently cost-saving compared with Semaglutide, supporting its potential as a lower-cost alternative treatment.