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expert reaction to insulin for type 2 diabetes and risk of death

A paper published in the journal Diabetes, Obesity and Metabolism explored an association between treatment of patients with type 2 diabetes with insulin, and risk of death. They report an increased incidence of mortality, major adverse cardiovascular events, and cancer in those treated with insulin, and suggest their results warrant further study.


Prof. Sir David Spiegelhalter, Winton Professor of the Public Understanding of Risk, University of Cambridge, said:

“Unfortunately this study cannot answer the crucial question: are patients taking more insulin because they are sicker? If so, this could explain the association.”


Mr Simon O’Neill, Director of Health Intelligence, Diabetes UK, said:

“As diabetes is a progressive condition, those on larger doses of insulin may have had the condition for longer and have other underlying health problems that we do not understand and so we would need further, more robust, research before we could be confident that insulin really does increase risk of early death.

“But while the real-world relevance of this study is unclear, what is beyond doubt is that if you have Type 2 diabetes then maintaining consistently low blood glucose levels is vital for reducing risk of devastating complications such as blindness, amputation and stroke and, ultimately, early death. This is why insulin is an essential treatment and we would stress that it is incredibly important that people who have been prescribed insulin by their doctor continue to take it.”


Prof. Simon Thompson, Director of Research in Biostatistics, University of Cambridge, said:

“Observational studies like this are prone to limitations, because of confounding factors – we don’t know whether death risk is directly related to insulin dose, or rather just that some other factor may cause both the need for a high insulin dose and a greater risk of death. In this case, the patients with diabetes who are (or become) sicker may be those that get the higher insulin doses. So we can’t distinguish the effect of disease severity on death risk from the effect of insulin dose on death risk. The statistical adjustments that the authors perform cannot overcome the limitations of this type of study.”


Prof. Malcolm Alison, Professor of Stem Cell Biology, Barts and The London School of Medicine and Dentistry (QMUL), and former Head of The Centre for Diabetes at QMUL, said:

“In about one-third of patients with Type 2 diabetes, lifestyle changes and /or glucose-lowering drugs fail to normalize high blood glucose levels resulting in insulin being prescribed at a dose dependent on factors such as weight and blood glucose levels after fasting (such patients number over a quarter of a million in the UK).

“This study looked at six and a half thousand patients on insulin therapy alone over an average of just over 3 years, and after accounting for the risks associated with other diseases the patients may have had, concluded there was an increased risk of death, cardiovascular disease and cancer that was correlated with the patient’s cumulative insulin exposure. For example, cancer was diagnosed in nearly 6% of patients, indicative of an approximately 33% increased risk, though the risk almost doubled in some groups such as those with a history of vascular disease, or simply being male.

“As stated by the authors, any potential risks of insulin therapy need to be viewed in the context of the hormone’s undoubted benefits in achieving good glucose control, and further prospective interventional studies are required to clarify what is clearly a very complex relationship.”


‘Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer’ by S. E. Holden et al. published in Diabetes, Obesity and Metabolism on Wednesday 10 December 2014. 


Declared interests

None declared

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