1. A joint investigation by Channel 4 News and the BMJ reveals the NHS spends tens of millions more than necessary on modern insulins to treat diabetes despite guidance from NICE to use cheaper products. Wednesday 15 December 2010

2. How small changes led to big profits for insulin manufacturers BMJ Dec 2010 Amanda Adler, chair of the NICE guidance committee says: “I would estimate that around 90% of people with type 2 diabetes would probably do quite well on human insulins compared with the long acting insulin analogues”. Figures from the University of Cardiff collated for the BMJ and Channel 4 News suggest that if only 50% of those using analogue insulins had been put on human insulin instead the NHS would have saved close to £250m in the cost of insulin over the past five years.

3. How small changes led to big profits for insulin manufacturers BMJ Dec 2010 “We are about to convert the market from human insulin on to insulin analogue…globally, we have more than 40% of the market now converting to analogue. So we are actually in a different situation from most other companies. We are taking our portfolio from being generic product, human insulin, on to a patent protected insulin analogue.” Jesper Brandgaard, chief financial officer of Novo Nordisk, in an interview on CNBC in 2006.

4. Mixtard withdrawal Dec 2010 Novo Nordisk has announced that for commercial reasons, after years of manufacture Mixtard® 30 will be withdrawn from the UK market on 31.12.10. ‘DTB deplores the axing by Novo Nordisk of an insulin product, currently used by an estimated 90,000 diabetics in the UK….it calls on manufacturer Novo Nordisk to reverse its decision to withdraw Mixtard 30 from sale by the end of this year. One estimate suggesting that a straight switch to NovoMix 30 for patients in England alone would add around £9 million to the NHS drugs bill. Also costs in the need to review many thousands of patients to switch treatment, some of whom will need many months to become established on an alternative insulin’. Dr I Iheanacho Drug and Therapeutics Bulletin

5. NICE Clinical Guideline T2DM 87 May 2009 Initiate insulin therapy from a choice of a number of insulin types and regimens. Begin with human NPH insulin injected at bed-time or twice daily according to need. Consider, as an alternative, using a long-acting insulin analogue if: –Assistance with injection from a carer or HCP is needed & injection frequency can be reduced from twice a day to once a day or –the person’s lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes, or –the person would otherwise need twice-daily NPH insulin injections in combination with oral glucose- lowering drugs, or –the person cannot use the device to inject NPH insulin.

6. NICE Clinical Guideline T2DM 87 May 2009 Consider twice-daily pre-mixed (biphasic) human insulin (particularly if HbA1c ≥ 9.0%). A once-daily regimen may be an option. Consider pre-mixed preparations that include short- acting insulin analogues, rather than pre-mixed preparations that include short-acting human insulin preparations, if: –a person prefers injecting insulin immediately before a meal, or –hypoglycaemia is a problem, or –blood glucose levels rise markedly after meals.

7. NICE Clinical Guideline T2DM 87 May 2009 Consider switching to a long-acting insulin analogue (insulin detemir, insulin glargine) from NPH insulin in people where: target HbA1c not reached because of significant hypoglycaemia, or significant hypoglycaemia on NPH insulin irrespective of the level of HbA1c reached, or device needed to inject NPH insulin is difficult to use but who could administer their own insulin safely and accurately if a switch to a long-acting insulin analogue were made, or help from a carer or HCP is needed to administer insulin injections and for whom switching to a long-acting insulin analogue would reduce the number of daily injections

8. NICE Clinical Guideline T2DM 87 May 2009 Main benefits analogues: less hypoglycaemia & once daily injection Analogue vs NPH –No difference in HbA1c –Lower rate any hypoglycaemia RR=0.89 (95%CI 0.63-0.96) Glargine RR=0.68 (95%CI 0.54-0.86) Detemir -Lower rate nocturnal hypoglycaemia RR=0.54 (95%CI 0.43-0.69) Glargine RR=0.54 (95%CI 0.42-0.68) Detemir -No difference in rates severe hypoglycaemia

9. NICE Clinical Guideline T2DM 87 May 2009 Cost effectiveness analysis of glargine & detemir vs NPH found insulin analogues more effective but more costly All ICERs outside conventional cost effectiveness limits GDG noted that long acting insulin analogues did not appear to be cost effective options compared to NPH GDG accepted that episodes of hypoglycaemia have the potential to be highly detrimental to a person’s health related QoL (partly because of the fear of symptomatic hypoglycaemic episode) More cost effective to target use to people most likely to benefit

10. SIGN 116 Guideline Ch. 6 T2DM March 2010 When starting insulin therapy as a single injection before bed-time, NPH insulin is as effective in reducing HbA1c as basal insulin analogue therapy. However, basal insulin analogue therapy is associated with fewer episodes of nocturnal and overall hypoglycaemia No difference was seen for severe hypoglycaemia. Collating evidence from six short term trials, it was necessary to treat eight patients with type 2 diabetes with glargine compared with NPH (continuing oral agents) to avoid one episode of nocturnal hypoglycaemia. Weight gain was slightly less with detemir than with NPH insulin when added to oral glucose-lowering agents (1 kg, 95% CI -1.69 to -0.23 kg).

11. SIGN 116 Guideline Ch. 6 T2DM March 2010 In a UK Health Technology Assessment of newer drugs for blood glucose control in type 2 diabetes, the incremental cost per quality adjusted life year (QALY) gained for use of glargine in place of NPH insulin was estimated at £320,029; for detemir the equivalent cost estimate was £417,625. SIGN Recommendation: Once daily bedtime NPH insulin should be used when adding insulin to metformin and/or sulphonylurea therapy. basal insulin analogues should be considered if there are concerns regarding hypoglycaemia risk

12. 12 How are we doing?

13. Analogue items as % all insulin ranked by prevalence Jan-Mar 2010

14. Insulin cost as % all insulin ranked by prevalence Jan-Mar 2010