Insulin analogues were developed in an attempt to overcome the problems associated with human insulin, ie slow and prolonged absorption of meal-time insulin, and unduly short absorption of basal insulin, both often rather unpredictably, and thus leading to hyper- and hypo-glycaemia (Holt, 2009).
Analogues have been available for use by people with diabetes since the introduction of the first rapid-acting analogue, insulin lispro, in the mid 1990s. Since then, two additional rapid-acting analogues (insulin aspart and insulin glulisine) and two long-acting analogues (insulin detemir and insulin glargine) have entered the clinical arena. Rapid-acting analogues (lispro and aspart) are also available in premixed insulin preparations, and other analogues are in an advanced state of development.
Since their introduction, analogues have become increasingly popular for use in clinical practice despite their considerably higher cost. Questions have been raised as to whether their benefits outweigh these higher costs. Although costs are of increasing importance within the current climate in the NHS, we are concerned that cost should not become the only criteria on which prescribing decisions are made although it has to be a consideration.
We would support The National Institute of Health and Clinical Excellence (NICE) conclusions that insulin analogues should be available to people with diabetes, (NICE CG15 2004, NICE CG66 2008, NICE CG87 2009), albeit with restrictions, especially for those with Type 2 diabetes. For people starting insulin, human insulins are recommended as first line treatment, switching to analogues for optimal control as recommended by NICE (for a summary of those recommendations, please download the full position statement [PDF, 85KB]). Those already on analogue insulins should not have their treatment changed if already well controlled.
Diabetes UK has reviewed the evidence relating to the use of insulin analogues in both Type 1 and Type 2 diabetes. While there is limited evidence that insulin analogues improve HbA1c, there is good evidence that some rapid acting analogues reduce postprandial glucose levels, while long acting analogues may improve fasting glucose levels, leading to reduced hypoglycaemia (especially nocturnal), and less weight gain, particularly in people with Type 2 diabetes.
- Fear of hypoglycaemia is a determinant of treatment concordance (Gough 2006), so any reduction in episodes of hypoglycaemia is likely to improve concordance and therefore diabetes management, reducing the chances of developing the long term complications of diabetes.
- Fear of hypoglycaemia has marked effects on health-related quality of life (Currie et al 2006, Vexiau et al 2008).
- The wider impact of mild hypoglycaemia should also not be underestimated, as it has a measurable impact on productivity and costs for both employers and employees.
- Weight management is the primary nutritional strategy in managing glucose control in people with Type 2 diabetes who are overweight or obese (Dyson et al 2011) so insulins that effectively control blood glucose but with lesser weight gain should be considered.
- Post-prandial glucose level is a direct and independent risk factor for cardiovascular disease and a reduction in post-prandial levels is important for people with diabetes, who are already at increased risk of CVD (IDF Guideline Group, 2007).
While clinical trails provide the best quality of data for assessing a drug’s efficacy, certain limitations to the literature reviewed must be taken into consideration. Most trials into insulin analogues were not designed to demonstrate superiority in blood glucose management, merely equivalence (Plank 2005, Sheldon 2009) although a trial published by Hermansen (2004) showed slight superiority. Some trials had HbA1c as a secondary endpoint. There are also difficulties in interpreting the data, as terms such as severe hypoglycaemia are open to bias-prone definitions (Horvath 2007). Finally, trial populations tend to be more motivated and different results may be found in clinical practice (Holt 2009).
What Diabetes UK recommends:
Diabetes UK recommends that all insulin analogues should be available to people with diabetes in the same way as human or animal insulin. The decision of which insulin is most appropriate should be made in consultation between the person with diabetes and their healthcare team and should follow NICE guidance.ie human insulins should, in general, be tried as first line treatment, with analogues being introduced if optimal control cannot be attained.
This position statement relates to the use of analogue insulins when commencing insulin therapy rather than changes in prescribing policy of those already well controlled on analogue insulins. Diabetes UK recommends that people who are already established on analogue insulin and well controlled should continue with their treatment.
Diabetes UK would like to see pharmaceutical companies addressing the issue of cost to ensure that new and novel therapies are affordable in the current climate and are supported by robust evidence of superiority to established therapies.
For review in 2013
Download
Download the full position statement on analogue insulin (PDF, 85KB), including references and a summary of NICE guidance.