Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: findings from a 5 year randomised, open-label study

Abstract

Abbreviations MedDRA Medical Dictionary for Regulatory Activities NPH Neutral protamine HagedornTo the Editor: We have reported a randomised, long-term safety study comparing the effects of using the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) versus human neutral protamine Hagedorn (NPH) insulin for 5 years in the management of type 2 diabetes [1]. The study, in which 1017 patients were randomised and treated, was designed to assess ocular complications of diabetes: there was no excess of such effects with insulin glargine compared with NPH insulin treatment and there was a similar slow progression of diabetic retinopathy with both types of insulin. Because of recent concerns about postulated neoplastic effects of insulins [2-5], we report here additional information from our study that bears on this question. In total, the mean cumulative exposure in our study was more than 4 years (1,524 days in the insulin glargine group and 1,522 days in the NPH insulin group), with more than 70% of patients exposed to more than 4 years of treatment (76% and 71%, respectively) ( Table 1).The baseline demographics and diabetes status were similar between the two treatment groups (insulin glargine vs NPH insulin): diabetes duration (10.7 vs 10.8 years),

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

“…Both classes of agents increase insulin levels, and sulfonylureas have been associated with higher cancer risk (41,60,61). Likewise, insulin, particularly glargine, has been associated with an increased cancer risk in some (62)(63)(64)(65), but not all (66,67), epidemiologic studies; thus, the true protective effect of metformin cannot be estimated. The observation that a different class of insulin-lowering agents such as thiazolidenediones were not associated with reduced cancer risk in two studies suggests that the full anticancer effect of metformin is not due solely to reductions in insulin or that thiazolidenediones have cancer-promoting effects that counteract the reductions in insulin that are usually seen with those agents.…”

The longest ever randomised controlled trial of insulin glargine: study design and HbA1c findings

“…The authors did not report the use of OHAs at all, except for one remark in the discussion and a post hoc analysis, which was intended to explain the difference in HbA 1c levels; thus, treatment exposure patterns were not clear. Detailed reporting of concomitant metformin is particularly important with respect to the follow-up cancer risk data [2], since metformin is associated with almost complete attenuation of cancer risk [3]. We know that insulin glargine users are more likely than other insulin analogue users, including insulin detemir (NN304) [B29Lys(ε-tetradecanoyl),desB30 human insulin] users, to also receive metformin in a basal/ oral combination [4].…”

Untitled

“…Clinical evidence from a retrospective, pooled analysis of 31 randomized controlled trials (12 in Type 1 diabetes and 19 in Type 2 diabetes), which included a total of 10 880 people, found no increase in the risk of cancer with insulin glargine vs. comparator treatments [64] . In addition, results of a 5-year prospective study showed no increased risk of mitogenicity in terms of DR or neoplasms for insulin glargine relative to NPH insulin in patients with Type 2 diabetes [61,63] . Therefore, although continuing studies will monitor mitogenicity over long-term use, current data suggest that binding of insulin glargine to the insulin or IGF-1 receptors seems to pose no greater risk for adverse mitogenic or metabolic eff ect vs. human insulin or NPH insulin, when used in people at physiological concentrations.…”