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

University of Texas Southwestern Medical School, Dallas, TX, USA, .
Diabetologia (Impact Factor: 6.67). 08/2009; 52(9):1971-3. DOI: 10.1007/s00125-009-1452-2
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Available from: Julio Rosenstock, Mar 17, 2014
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    • "To date, the advantage of long-acting analogues has not been confirmed in long-term controlled studies under conditions similar to clinical practice. The completion of a 5-year randomized study comparing the effects of glargine versus NPH as basal insulin on progression of retinopathy in patients with T2DM (Rosenstock, Fonseca, McGill, et al., 2009a) provided an opportunity to examine this issue in a long-term setting, as has been done previously for other issues of interest (Rosenstock, Fonseca, McGill, et al., 2009b). The original analysis of the study showed a lower risk of hypoglycemia with glargine compared with NPH, without any differences in the rate of progression of diabetic retinopathy (Rosenstock, Fonseca, McGill, et al., 2009a). "
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    ABSTRACT: Aims This analysis evaluated HbA1c-adjusted hypoglycemia risk with glargine versus neutral protamine Hagedorn (NPH) over a 5-year study in patients with Type 2 diabetes mellitus (T2DM). Clinical significance was assessed using number needed to harm (NNH) to demonstrate the risk of one additional patient experiencing at least one hypoglycemic event. Methods Individual patient-level data for symptomatic documented hypoglycemia and HbA1c values from a 5-year randomized study comparing once-daily glargine (n = 513) with twice-daily NPH (n = 504) were analyzed. Symptomatic hypoglycemia was categorized according to concurrent self-monitoring blood glucose levels and need for assistance. Hypoglycemic events per patient-year as a function of HbA1c were fitted by negative binomial regression using treatment and HbA1c at endpoint as independent variables. An estimate of NNH was derived from logistic regression models. Results The cumulative number of symptomatic hypoglycemia events was consistently lower with glargine compared with NPH over 5 years. Compared with twice-daily NPH, once-daily glargine treatment resulted in significantly lower adjusted odds ratios (OR) for all daytime hypoglycemia (OR 0.74; p = 0.030) and any severe event (OR 0.64; p = 0.035), representing a 26% and 36% reduction in the odds of daytime and severe hypoglycemia, respectively. Our model predicts that, if 25 patients were treated with NPH instead of glargine, then one additional patient would experience at least one severe hypoglycemic event. Conclusions This analysis of long-term insulin treatment confirms findings from short-term studies and demonstrates that glargine provides sustained, clinically meaningful reductions in risk of hypoglycemia compared with NPH in patients with T2DM.
    Journal of Diabetes and its Complications 09/2014; 28(5). DOI:10.1016/j.jdiacomp.2014.04.003 · 3.01 Impact Factor
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    • "In contrast, the oncogenic effect of hyperinsulinemia might be offset by the cancer‐protective effect through amelioration of hyperglycemia. RCTs and more recent cohort studies have not shown significant associations of insulin with cancer risk57. "
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    ABSTRACT: A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.
    Journal of Diabetes Investigstion 05/2013; 4:225-232. DOI:10.1111/jdi.12068 · 1.83 Impact Factor
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    • "A randomized, open-label, long-term safety study, designed to assess ocular complications of diabetes, showed that there was no evidence of a greater risk of the development or progression of diabetic retinopathy with insulin glargine versus NPH insulin treatment in patients with type 2 diabetes (Rosenstock et al., 2009a). Although the study was not designed to investigate the effects of treatment on the frequency of tumour development, its long duration allowed the comparative assessment of the occurrence of malignancies with the two treatments (Rosenstock et al., 2009b). In this study, during a 4.2-year follow-up of 1017 patients, there were 20 and 31 patients with incident cancer in the insulin glargine and NPH insulin groups, respectively, indicating that the overall risk of malignancy appears to be similar for both insulins in patients with type 2 diabetes (Rosenstock et al., 2009b). "
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    ABSTRACT: Context: Retrospective, observational studies have reported an association between diabetes treatment with insulin and a higher incidence of cancer. Objective: Overview the literature for in vitro and in vivo studies of the metabolic and mitogenic properties of basal insulin analogues and assess the implications for clinical use. Methods: Relevant studies were identified through PubMed and congress abstract database searches; data on metabolic and mitogenic signalling in relation to insulin treatment of diabetes are included in this review. Results: The balance of evidence shows that although some analogues have demonstrated mitogenic potency in some in vitro studies in cancer cell lines, these findings do not translate to the in vivo setting in animals or to the clinical setting in humans. Conclusions: The current consensus is that there is no clinical or in vivo evidence to indicate that any commercially available insulin analogue has carcinogenic effects. Large-scale, prospective clinical and observational studies will further establish any potential link.
    Archives of Physiology and Biochemistry 02/2013; 119(1):1-14. DOI:10.3109/13813455.2012.754474 · 1.76 Impact Factor
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