NPC Archive Item: Insulin analogues cost NHS millions

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24 October 2011

A UK study found that if all analogue insulin dispensed in the UK between 2000 and 2009 had been for human insulin alternatives, the NHS would have saved an estimated £625 million. The adjusted annual cost of analogue insulin increased from £18 million in 2000 (12% of total insulin cost) to £305 million in 2009 (85% of total insulin cost).

Level of evidence:
Level 3 (other evidence) according to the SORT criteria.

In type 2 diabetes in particular, the effect of NICE guidance ought to be that long-acting insulin analogues and biphasic insulins containing short-acting insulin analogues are not used routinely. However, the prescribing data for England shows that the uptake of insulin glargine, insulin detemir, biphasic insulin aspart (and to a lesser degree biphasic insulin lispro) is extensive.

Health professionals should continue to follow NICE guidance on the management of type 2 diabetes. If insulin therapy is considered appropriate, it should be initiated with human NPH insulin (isophane insulin) injected at bed-time or twice daily according to need. Insulin analogues should be considered only in specific circumstances, such as in patients who require assistance from a carer or healthcare professional to administer their insulin injections, or those with problematic hypoglycaemia.

The NPC Key Therapeutics Document, written in support of the Quality, Innovation, Productivity and Prevention (QIPP) workstream includes recommendations to review, and where appropriate, revise the prescribing of long-acting insulin analogues in type 2 diabetes to ensure prescribing is in line with NICE guidance.

What is the background to this?
In type 2 diabetes, the preferred basal insulin recommended by NICE is human NPH insulin. Long-acting insulin analogues are recommended by NICE in specific patient circumstances, such as if assistance from a carer or health professional is needed to inject insulin, and use of a long-acting insulin analogue would reduce the frequency of injections from twice to once daily, or if the patient’s lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes. However, for most people with type 2 diabetes, long-acting insulin analogues offer no significant advantage over human NPH insulin and are much more expensive.

In terms of HbA1c lowering, there is no difference between long-acting insulin analogues and NPH insulin. The main benefits of long-acting insulin analogues over NPH insulin relate to their lower rates of hypoglycaemia, and their once daily compared with twice daily use (although NPH insulin can also be used once daily). However, these potential benefits need to be balanced against there much higher costs.

The cost-effectiveness analysis conducted for the NICE type 2 diabetes guideline found the long-acting insulin analogues, insulin glargine or insulin detemir, were more effective than NPH insulin but they were also more costly. All the incremental cost-effectiveness ratios (ICERs) were outside conventional limits of cost effectiveness, with ICERs ranging from about £100,000 to £400,000 per quality-adjusted life year (QALY) depending on the scenario they are used in. These are substantially greater than the £20,000 to £30,000 per QALY threshold usually considered in NICE’s cost-effectiveness evaluation.

Since their launch, the use of insulin analogues (short-acting analogues, e.g. insulin aspart, insulin glulisine and insulin lispro; long-acting analogues, e.g. insulin detemir and insulin glargine, biphasic insulin aspart and biphasic insulin lispro) has increased steadily. The aim of this study was to characterise the pattern of insulin prescriptions dispensed between 2000 and 2009, for the whole of the UK, and to evaluate the marginal financial cost to the NHS of using analogue insulin instead of its equivalent human insulin preparation.

What does this study claim?
Over the 10-year period, the NHS spent £1,629 million on analogue insulin, £1,056 million on human insulin and £47 million on animal insulin. The annual cost of analogue insulin increased from £18 million in 2000 (12% of total insulin cost) to £305 million in 2009 (85% of total insulin cost). During the same period, the annual cost of human insulin fell from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). See figure 1 below.

If it was assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin over the 10-year period was £625 million. This reduced to £312 million if an assumption was made that 50% of patients could have received human insulin instead.

In 2009, the last year studied, of the £51 miilion spent on human insulin, it was estimated that £39 million of the cost was for type 2 diabetes and £12 million was for type 1 diabetes. Of the £305 million spent on analogue insulin in 2009, £190 million was estimated to be for type 2 diabetes and £115 million for type 1 diabetes.

All costs were adjusted for inflation and reported in UK pounds at 2010 prices.

Figure 1: Total annual cost of insulin prescriptions for the UK, 2000 to 2009. NIC, net ingredient cost
From: Holden SE, et al. Evaluation of the incremental cost to the National health Service of prescribing analogue insulin. BMJ Open 2011;2:e000258.

So what?
This study has inherent limitations around the calculation of the incremental cost of analogue insulin, and the fact that prescription cost analyses such as these only include information on how much insulin was dispensed and not how many prescriptions were collected by patients with type 1 or type 2 diabetes. The authors estimated that the volume of analogue and human insulin dispensed to patients with type 2 diabetes is ‘far greater’ than for type 1 diabetes. However, there is no definitive figure on how many patients with type 2 diabetes could have received human insulin instead of analogue insulin.

Despite these limitations, the authors conclude that given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin (particularly NICE guidance for type 2 diabetes) would have resulted in considerable financial savings over the 10-year period.

Despite a lack of evidence of benefit in terms of HbA1c levels or patient oriented outcomes in type 2 diabetes, and a lack of long term safety data, expensive long-acting insulin analogues are increasingly prescribed instead of human NPH insulin. This is illustrated in figure 2 below taken from a recently updated NHS Information Centre Report looking at primary care prescribing trends for the treatment of diabetes from April 2005 to March 2011. The authors of this recent study cite several possible reasons for the increased use of analogue insulin over human insulin including successful marketing, analogues being available in new devices which may be more appealing to patients and easier to use, and the withdrawal of some human insulin products.

Figure 2. Net Ingredient Cost of selected non-biphasic intermediate and long-acting insulins, April 2005 – March 2011
From: The NHS Information Centre, Prescribing and Primary Care Services. Prescribing for Diabetes in England: 2005/6 to 2010/11. August 2011

In March 2011, a prescribing comparator around the use of long-acting insulin analogues was introduced to support the QIPP workstream. This comparator shows the variation across PCTs in the prescribing of insulin detemir and insulin glargine as a percentage of all items of long and intermediate acting insulins (excluding biphasic insulins). Figure 3 below shows the variation by PCT for this comparator in 2010/11. The percentage ranged from 38.0% up to 98.6% with the average PCT percentage being 85.3%. For more information on this QIPP comparator and the issues surrounding the use of long-acting insulin analogues in type 2 diabetes, see the recently published NPC elearning materials on this topic.

Figure 3. Percentage of long acting human analogue insulin detemir and glargine items as a proportion of all long and intermediate acting insulin (excluding biphasic insulin) items prescribed, by PCT, 2010/11
From: The NHS Information Centre, Prescribing and Primary Care Services. Prescribing for Diabetes in England: 2005/6 to 2010/11. August 2011

In summing up their analyses, the authors of the current study state, “the rise of insulin analogues has had a substantial financial impact on the NHS, yet over the same period there has been no observable clinical benefit to justify that investment. It is likely that there is considerable scope for financial savings.”

Study details
Holden SE, et al. Evaluation of the incremental cost to the National health Service of prescribing analogue insulin. BMJ Open 2011;2:e000258

Open-source data from the four UK prescription pricing agencies in England, Northern Ireland, Scotland and Wales from 2000 to 2009 were analysed. Data were grouped according to molecular origin (analogue, human and animal) and individual insulin types (insulin soluble, insulin isophane, insulin zinc suspension crystalline, biphasic isophane insulin, protamine zinc insulin, insulin aspart, insulin lispro, insulin detemir, insulin glargine, biphasic insulin aspart, biphasic insulin lispro and insulin glulisine). Cost was adjusted for inflation and reported in UK pounds at 2010 prices. The incremental cost of analogue insulin was calculated by summing the net ingredient cost of analogue insulin and then subtracting the cost of dispensing the same volume of insulin of human origin.

Outcomes and results
See above


Further information can be found on NHS Evidence and in the type 2 diabetes and type 1 diabetes e-learning sections of NPC

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