insulin-detemir and Neoplasms

Human serum albumin (HSA) has emerged as a versatile carrier for therapeutic agents, primarily for treating diabetes and cancer, improving the pharmacokinetic profile of the drug or delivering the drug to the pathogenic site addressing diseases with unmet medical needs. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir, Tresiba, and Victoza) which bind physically to the respective binding sites of HSA thus extending their half-life. For cancer treatment, the paclitaxel albumin nanoparticle Abraxane has been approved for treating metastatic breast cancer, non-small cell lung cancer, and advanced pancreatic cancer. Finally, the albumin-binding prodrug of doxorubicin, Aldoxorubicin, which binds covalently to the cysteine-34 position of circulating albumin, is in advanced clinical trials with a registration phase 3 trial for soft tissue sarcoma initiated in Q1 2014.

Topics: Albumin-Bound Paclitaxel; Albumins; Diabetes Mellitus; Doxorubicin; Drug Carriers; Humans; Insulin Detemir; Insulin, Long-Acting; Molecular Structure; Neoplasms; Paclitaxel; Serum Albumin

Recent epidemiological studies suggest that treatment with insulin glargine (A21Gly,B31Arg,B32Arg human insulin) may promote cancer growth. The present meta-analysis was performed to assess the risk of cancer during treatment with insulin detemir (B29Lys(epsilon-tetradecanoyl),desB30 human insulin), another long-acting insulin analogue.. This meta-analysis was performed in a population of 8,693 patients with type 1 or type 2 diabetes, who were included in Novo Nordisk-sponsored, randomised and controlled diabetes trials of at least 12 weeks in duration that compared insulin detemir with NPH insulin or insulin glargine. In a blinded manner, the adverse events with suspected treatment-emergent malignant tumours were obtained from these studies under three system-organ classes: 'Neoplasms benign, malignant and unspecified (including cysts and polyps)', 'Neoplasm' and 'Surgical and medical procedures'. Conditional ORs were estimated applying both the Mantel-Haenzel and Peto methods to ensure robustness of results.. Separate analyses were performed for trials comparing insulin detemir with NPH insulin and insulin detemir with insulin glargine. In the first analysis, 16 studies were included with a total of 3,983 patients treated with insulin detemir and 2,661 patients treated with NPH insulin. In the second analysis, five studies were included with a total of 1,219 patients treated with insulin detemir and 830 patients treated with insulin glargine. The estimated OR for a cancer diagnosis between NPH insulin and insulin detemir was statistically significantly >1, with the ratio favouring insulin detemir. There was a more than twofold higher cancer occurrence in the NPH insulin-treated population. For the insulin detemir comparison with insulin glargine, there was a non-significant difference in ORs in favour of insulin detemir.. In these randomised controlled diabetes trials, patients treated with insulin detemir had a lower or similar occurrence of a cancer diagnosis compared with patients treated with NPH insulin or insulin glargine, respectively.

Topics: Adult; Aged; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic

The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies.. National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin.. A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences.. The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Neoplasms; Regression Analysis; Young Adult

To explore in France the relationship between insulin glargine use and overall and specific cancer risks in type 2 diabetic patients compared with other basal insulins.. Data were extracted from French health insurance information system (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked with data from the French Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). Included were 70,027 patients aged 40-79 years who started a basal insulin in 2007-2009. Cox proportional hazards models with age as time-scale were used to calculate multivariate-adjusted hazard ratios for associations between type of basal insulin and risk of overall cancer, breast cancer, and seven other cancer sites.. The median follow-up was 2.67 years in patients exposed to insulin glargine. Absolute event rates for all cancer in patients exposed to glargine versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years, respectively. No significant association was observed between glargine exposure and overall cancer incidence after adjustment for sex, with a hazard ratio of 0.97 (95% CI 0.87-1.07), or after additional adjustment for any other hypoglycemic agent use and duration of diabetes. No increased risk of breast cancer was observed for glargine users compared with other basal insulins users, with a fully adjusted hazard ratio of 1.08 (0.72-1.62).. In a large cohort of patients newly treated by basal insulin, no increased risk of any cancer was observed in insulin glargine users compared with other basal insulin users. Because follow-up did not exceed 4 years, longer-term studies are needed.

Topics: Adult; Aged; Databases, Factual; Female; France; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasms