insulin-detemir and Breast-Neoplasms

To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes.. This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388) from September 2006 to September 2015, with follow-up through May 2017. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for incidence of breast cancer according to ever use, cumulative duration of use, cumulative dose of insulin, length of follow-up time, and a combination of dose and length of follow-up time.. Ever use of glargine was not associated with an increased risk of breast cancer compared with NPH (HR 0.97; 95% CI 0.88-1.06) or detemir (HR 0.98; 95% CI 0.92-1.05). No increased risk was seen with glargine use compared with either NPH or detemir by duration of insulin use, length of follow-up, or cumulative dose of insulin. No increased risk of breast cancer was observed in medium- or high-dose glargine users compared with low-dose users.. Overall, glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir in female Medicare beneficiaries.

Topics: Age Factors; Age of Onset; Aged; Aged, 80 and over; Breast Neoplasms; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Medicare; Retrospective Studies; United States

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

Topics: Aged; Breast Neoplasms; Canada; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Middle Aged; Risk

Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.. Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, 23 patients were treated with glargine plus rapid-acting insulin analogues, and similar doses of human NPH and rapid-acting insulin. For comparison, eight patients were treated with insulin detemir (Levemir) and human NPH. MCF-7 cells were incubated with 10% serum and proliferation was assessed after 72 hours.. Serum containing insulin glargine was 1.11(95% CI 1.05-1.18) fold more mitogenic than human insulin-containing serum (p < 0.005); mitogenicity of serum containing detemir was 0.99(95% CI 0.98-1.02) fold that of human insulin-containing serum.. The serum of diabetic patients was slightly stronger mitogenic when using glargine as compared to human insulin or detemir for treatment.

Topics: Breast Neoplasms; C-Peptide; Cell Line, Tumor; Cells; Chemotactic Factors; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pilot Projects; Risk Factors

Insulin analogues are widely used in the treatment of diabetes mellitus. Some insulin analogues were reported to display atypical activities in vitro that resemble those of insulin-like growth factor-I (IGF-I). The aim of this study was to investigate whether two long-acting insulin analogues [glargine (Lantus, Sanofi Aventis, Germany) and detemir (Levemir, Novo Nordisk, Denmark)] and two short-acting analogues [lispro (Humalog, Eli Lilly, Indianapolis, USA) and aspart (Novolog, Novo Nordisk, Denmark)] exhibit IGF-I-like activities on cultured cancer cells in comparison with IGF-I and regular human insulin.. HCT-116 (colorectal cancer), PC-3 (prostate cancer) and MCF-7 (breast adenocarcinoma) cell lines were treated with insulin, IGF-I or insulin analogues, and proliferation and protection from apoptosis were measured by cell counting and fluorescent-activated cell sorter (FACS) analysis, respectively. In addition, Western blots were used to identify signalling molecules activated by the analogues.. Glargine, detemir and lispro had proliferative effects that resemble IGF-I action. Insulin, however, did not stimulate cellular proliferation. In addition, glargine and detemir displayed an IGF-I-like anti-apoptotic activity. Glargine, like insulin and IGF-I, induced phosphorylation of both ERK and AKT, suggesting that the analogue is able to stimulate both the ras-raf-mitogen-activated protein kinase (MAPK) and PI3K-AKT pathways. Furthermore, glargine induced both insulin receptor (IR) and IGF-IR phosphorylation.. Glargine, detemir and lispro, unlike regular insulin, exhibit in vitro proliferative and anti-apoptotic activities in a number of cancer cell lines. These actions resemble some of the effects of IGF-I, a growth factor involved in cancer initiation and progression. Insulin had no increased IGF-I activity. The specific receptor/s involved in mediating analogues actions remains to be identified.

Topics: Adenocarcinoma; Apoptosis; Breast Neoplasms; Cell Division; Cell Line, Tumor; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin-Like Growth Factor I; Insulin, Long-Acting; Male; Prostatic Neoplasms; Tumor Cells, Cultured