Basal Insulin Regimens: Systematic Review, Network Meta-Analysis, and Cost - Utility Analysis for the National Institute For Health and Care Excellence (Nice) Clinical Guideline on Type 1 Diabetes Mellitus in Adults

Abstract

To assess the clinical and cost-effectiveness of basal insulin regimens for adults with type 1 diabetes mellitus (T1DM), from the English National Health Service (NHS) perspective, and inform NICE recommendation regarding optimal choice of basal insulin. We considered seven daily insulin regimens: neutral protamine hagedorn (NPH) (once (od), twice (bid) and four-times daily (qid)), detemir (od and bid), glargine (od) and degludec (od). A systematic review of randomised controlled trials (RCTs) published in Medline, Embase and Cochrane databases to August 2014 was undertaken. Relative effectiveness was assessed using Bayesian network meta-analysis (NMA) undertaken in WinBUGs. Two outcomes were analysed: change in haemoglobin A1c (HbA1c) and rate of severe/major hypoglycaemia. The cost-utility analysis (CUA) was undertaken using the IMS-CORE Diabetes Model (IMS-CDM), following NICE reference case (lifetime time horizon, 3.5% discount rate for both costs and QALYs (quality-adjusted life-years), net monetary benefit (NMB) calculated using a threshold of £20,000 per QALY gained). Sensitivity analyses were performed; including changing insulin dose, discount rate and cost of hypoglycaemic events. Twenty eight RCTs were included in the NMA. The mean change in HbA1c ranged from -0.48% (SE=0.10) for detemir-(bid) to –0.01% (SE=0.17) for NPH-(qid). Mean rate of severe/major hypoglycaemia ranged from 29 (95%CI: 0.00 to 39.76) to 35 (95%CI: 0.00 to 46.73) events/100 person-years. The CUA showed that detemir-(bid) had the highest mean QALY-gain (11.09) and NMB (£181,456) per patient. Insulin glargine-(od) ranked second. Insulin degludec-(od) was the most costly, with the highest treatment cost (£7,169). The optimal choice was robust to all changes except when high doses of detemir-(bid) were assumed (>30% increment compared to other regimens); where glargine-(od) ranked first. Insulin detemir administered twice daily was the optimal basal regimen for adults with T1DM from the English NHS perspective; providing the highest QALY gain and NMB among the regimens considered.