Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine

OBJECTIVES: The aim of this review was to evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.

METHODS: A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.

RESULTS: Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control.

Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily.

Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended ScHARR model. Three economic models are provided in the submission, two relating to type 1 diabetes (previously on other basal-bolus regimes or previously on premix therapies) and one relating to type 2 diabetes. All three models compare the cost–utility of insulin glargine against NPH insulin. In general, the structures of the models are poor. In all three models, mistakes relating to assumptions and calculations have been made. The industry submission concludes that insulin glargine is highly cost-effective in all three models.The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia. The industry submission explores this issue through a number of analyses and the claimed base case is based on the most favourable of these analyses. By changing this assumption, the cost per QALY ranges from cost-effective to not cost-effective.

CONCLUSIONS:The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes.