NPC Archive Item: Newer insulins have only limited clinical benefits

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23rd March 2009

A Canadian Heath Technology Assessment has concluded that the newer, insulin analogues offer little clinical advantage over older, conventional insulins in terms of glycaemic control or reduced hypoglycaemia for the management of patients with type 1, type 2 or gestational diabetes. These results are consistent with recommendations made by NICE.

Any decision to start an insulin analogue needs to be balanced carefully against the lack of long-term safety data and increased prescribing costs. In addition, people with glycaemic control problems should be properly assessed for underlying causes before these newer, more expensive insulins are considered. This includes education and checking understanding around how to manage their disease and treatment.

NICE guidance on the management of type 1 diabetes states that adults with type 1 diabetes should have access to the types of insulin they find allow them optimal well-being. They also recommend that children and young people with type 1 diabetes are offered the most appropriate insulin preparations according to their individual needs. However, NICE cautioned against switching patients with control problems onto the newer more expensive insulins without proper assessment of underlying causes. Such causes of poor control might include problems with the patient’s injection technique or inadequate knowledge and poor self-management skills.

NICE guidance on the management of type 2 diabetes recommends that, when insulin therapy is necessary, human NPH insulin is the preferred option. Insulin analogues can be considered for those who fall into specific categories e.g. those who require assistance from a carer or healthcare professional to administer their insulin injections, or those with problematic hypoglycaemia.

A NICE guideline on the use of newer agents for blood glucose control in type 2 diabetes, including the long-acting insulin analogues, insulin detemir and insulin glargine, is expected to be published in May 2009.

What does this study claim?
The Canadian review found that most estimates of differences in HbA1c between patients treated with conventional insulins and insulin analogues were not statistically significant. Where there were statistically significant differences in favour of insulin analogues, these differences may not have been clinically important. Some statistically significant benefits of insulin analogues were found in terms of hypoglycaemia for some comparisons, populations and types of hypoglycaemia. However, any clinical advantage over conventional insulins seems minor and of clinically debatable relevance. Few studies reported on patient satisfaction or quality of life. In addition, studies were not sufficiently powered or of adequate duration to measure differences in long-term diabetes-related complications or death.

So what?
The findings of this systematic review and meta-analysis are consistent with other evidence and add support to the recommendations made by NICE. Despite an increase in prescribing of the newer more expensive insulin analogues, there is still no strong evidence that they result in large improvements in HbA1C compared with older insulins.

Several studies that compared insulin analogues with conventional insulins have suggested that insulin analogues reduce hypoglycaemia, particularly at night. However, most trials of insulin analogues included in the meta-analysis had methodological limitations and were of poor quality. The majority were sponsored by the industry. All studies were open-label, not double-blinded, and short-term, ranging from 4 weeks to 30 months. Allocation concealment was rarely described. In addition there was significant heterogeneity across the study methods, populations, outcomes and results.

In the absence of long-term safety data over many years, it is reasonable not to support a wide-spread policy of using insulin analogues first-line in most patients. Nevertheless, they still have a valuable role in managing specific patients, particularly those whose glycaemic control is suboptimal with older insulins, especially if they have problematic hypoglycaemia.

A Commentary accompanying the study points out that structured programmes for self-management training of patients with type 1 and type 2 diabetes have shown a more pronounced, clinically relevant and sustained improvement in glycaemic control and a reduction in the risk of severe hypoglycaemia compared with the relative benefit observed to date with insulin analogues.

Further details on the management of type 1 and type 2 diabetes are available on NPC. In addition a MeReC Bulletin has summarised the role of newer insulins in diabetes. Although this was published in 2007, the key messages regarding newer insulins are essentially unchanged.

Singh SR, Ahmad F, Lal A, et al. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis.  CMAJ 2009;180:385–97

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