IQWiG: Short-acting insulin analogues are not superior to regular ‘human’ insulin in Type 2 diabetes

July 2006

Report from the Institute for Quality and Efficiency in Health Care [IQWIG]
This organisation is Germany’s equivalent to NICE in the UK and its final report on the use of rapid-acting analogues for the treatment of Type 2 diabetes resulted in the following recommendations:

"For patient relevant outcomes, there is no convincing evidence of a superiority of rapid-acting insulin analogues compared to regular human insulin [short-acting] in diabetes mellitus type 2 therapy. Rapid acting insulin analogues have not been sufficiently investigated with regard to their potential long-term beneficial and harmful effects."

The key points in the Report summary are:

No relevant and fully published study was found on insulin aspart [NovoRapid] only an abstract in 1999 and Novo Nordisk was not prepared to provide study data if these data were to be published in this report. No relevant studies were found on pre-mixed formulations of rapid-acting insulin analogues or short-acting human insulin combined with longer-acting insulins. [Important lack of research considering Novo Nordisk’s removal of pre-mixed human insulins in the UK!]

  • None of the studies were designed to investigate the effect of rapid-acting insulin analogues on the reduction of diabetic complications or total mortality.
  • For hypoglycaemia, no clear advantage was shown with analogues compared to human insulin with regard to severe, symptomatic or nocturnal hypoglycaemia.
  • Quality of life studies were limited but no clear advantage was shown with analogues compared to human insulin and no definite conclusions could be drawn about patient satisfaction as the studies were unsatisfactory.
  • There was a tendency towards more people dropping out of the studies due to adverse reactions in those treated with analogues compared with those on human insulin.
  • In so far as reported, there were similar weight increases for both patients receiving analogues and those receiving human insulin.
  • As the maximum study period was 12months, no studies could show the safety of long-term use of analogues in people with Type 2 diabetes. Unless proved otherwise by adequately designed studies, the potential for mitogenic potency of insulin analogues [cell mutiplication and formation of tumours] as described in pre-clinical trials, is to be seen as a potential safety risk for long-term treatment of people with Type 2 diabetes.

The full report is available in English online at:

www.iqwig.de/index.media.538df941a1d274bea0b8b1f9ae06921b.pdf.

As a result of this review and the significant additional cost of insulin analogues, health providers in Germany made the decision not to fund rapid-acting insulins for people with Type 2 diabetes. This resulted in the insulin manufacturers lowering the price to that of short-acting ‘human’ insulin.