Insulin resistance and increased risk for malignant neoplasms: confounding of the data on insulin glargine

Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues. Reply to Nagel JM, Mansmann U, Wegscheider K et al. [letter] and Simon D [letter]

“…Nevertheless, in 1998 the prevalence of insulin-treated diabetes mellitus has been estimated to be 1.1% for men and 1.4% for women (aged 18 to 79 years) in Germany [3]. These proportions correspond well with the proportions mentioned by Nagel et al [1] for our study.…”

“…To the Editor: Nagel et al [1] raise a number of questions regarding the analyses in our paper [2]; these analyses, in their opinion, led to confounded measures of association. We agree that potential confounding plays an essential role and can never be completely ruled out in analyses of observational data.…”

“…The main concern of Nagel et al [1] is their assumption of an unequal distribution of patients with type 1 and type 2 diabetes in the insulin glargine (A21Gly,B31Arg,B32Arg human insulin) and human insulin groups. They seem to have overlooked the sensitivity analysis reported in our article that included only patients with a history of prescription of oral glucose-lowering agents (Table 4 in [2]).…”

“…This fact rules out the suspicion that our results are caused by the presence of a higher percentage of type 1 diabetic patients in the human insulin group. Nagel et al [1] further hypothesise that bias is introduced by ignoring intrinsic insulin production in patients in the insulin glargine group. However, in patients receiving high doses of insulin, intrinsic insulin production becomes negligible; hence, such a bias would be expected to be greatest in patients receiving relatively small doses of insulin.…”

“…Nagel et al [1] correctly state that a notable percentage of patients were not included because the date of study inclusion and the date of their first event was identical. This is explained by the fact that, in this context, censoring because of study end was also counted as an event.…”