Controversies in the use of insulin analogues

Introduction: In recent years, insulin analogues have been developed in order to improve the pharmacological parameters of insulin and to better mimic endogenous insulin output. Given that some of the modifications introduced into insulin analogues are located in a domain involved in a potential interaction with the insulin-like growth factor-I receptor (IGF-IR), it has been postulated that certain analogues may display IGF-I-like activities. Areas covered: We review the recent literature investigating the risk of malignant neoplasms and mortality in diabetic patients treated either with human insulin or with one of three insulin analogues (lispro, aspart, and glargine). We examine how critical analyses are consistent with the notion that the use of insulin glargine is associated with a possible increased risk of tumors in humans. Expert opinion: The introduction of insulin analogues has had a major impact in diabetes care. However, the benefit of some of these new insulins for the patient has yet to be demonstrated. Furthermore, research is needed to clarify whether insulin glargine is more strongly associated with cancer risk compared with other insulins.

[1]  H. Werner,et al.  Long-acting insulin analogues elicit atypical signalling events mediated by the insulin receptor and insulin-like growth factor-I receptor , 2010, Diabetologia.

[2]  Eva Frei,et al.  Native albumin for targeted drug delivery , 2010, Expert opinion on drug delivery.

[3]  Edward Giovannucci,et al.  Diabetes and Cancer , 2010, Diabetes Care.

[4]  D. Balzi,et al.  Doses of Insulin and Its Analogues and Cancer Occurrence in Insulin-Treated Type 2 Diabetic Patients , 2010, Diabetes Care.

[5]  G. Pandini,et al.  Insulin analogues differently activate insulin receptor isoforms and post-receptor signalling , 2010, Diabetologia.

[6]  D. Mayer,et al.  Treatment with insulin glargine (Lantus®) increases the proliferative potency of the serum of patients with type-1 diabetes: a pilot study on MCF-7 breast cancer cells , 2010, Archives of physiology and biochemistry.

[7]  M. Pollak,et al.  Insulin analogues and cancer risk: cause for concern or cause célèbre? , 2010, International journal of clinical practice.

[8]  P. Butler Insulin Glargine Controversy: A Tribute to the Editorial Team at Diabetologia , 2009, Diabetes.

[9]  J. Råstam,et al.  No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis , 2009, Diabetologia.

[10]  P. Home,et al.  Combined randomised controlled trial experience of malignancies in studies using insulin glargine , 2009, Diabetologia.

[11]  I. Hirsch,et al.  Insulin glargine and cancer--an unsubstantiated allegation. , 2009, Diabetes technology & therapeutics.

[12]  L. Smeeth,et al.  Insulin glargine and malignancy: an unwarranted alarm , 2009, The Lancet.

[13]  E. Gale Insulin glargine and cancer: another side to the story? , 2009, The Lancet.

[14]  J. McGill,et al.  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 , 2009, Diabetologia.

[15]  H. Colhoun,et al.  Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group , 2009, Diabetologia.

[16]  G. Steineck,et al.  Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden , 2009, Diabetologia.

[17]  D. Mayer,et al.  Proliferative effect of Apidra® (insulin glulisine), a rapid-acting insulin analogue on mammary epithelial cells , 2009, Archives of physiology and biochemistry.

[18]  L. Hemkens,et al.  Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study , 2009, Diabetologia.

[19]  V. Ehemann,et al.  Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines. , 2009, Endocrine-related cancer.

[20]  A. Lal,et al.  Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis , 2009, Canadian Medical Association Journal.

[21]  H. Werner,et al.  Insulin analogues display IGF‐I‐like mitogenic and anti‐apoptotic activities in cultured cancer cells , 2009, Diabetes/metabolism research and reviews.

[22]  J. Eckel,et al.  IGF-1 receptor signalling determines the mitogenic potency of insulin analogues in human smooth muscle cells and fibroblasts , 2007, Diabetologia.

[23]  F. Holleman,et al.  Nice insulins, pity about the evidence , 2007, Diabetologia.

[24]  M. Kellerer,et al.  Comparison of the Mitogenic Potency of Regular Human Insulin and its Analogue Glargine in Normal and Transformed Human Breast Epithelial Cells , 2007, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[25]  P. Raskin,et al.  Novel insulin analogues and its mitogenic potential , 2006, Diabetes, obesity & metabolism.

[26]  G. Bock,et al.  Biology of IGF-1: Its Interaction with Insulin in Health and Malignant States , 2004 .

[27]  Daniela Barlocco Insulin glulisine. Aventis Pharma. , 2003, Current opinion in investigational drugs.

[28]  A. Bube,et al.  Evaluation of the Carcinogenic Potential of Insulin Glargine (LANTUS) in Rats and Mice , 2002, International journal of toxicology.

[29]  Z. Laron,et al.  Insulin-like growth factor 1 (IGF-1): a growth hormone , 2001, Molecular pathology : MP.

[30]  P. Brunetti,et al.  Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. , 2000, Diabetes.

[31]  H. Yki-Järvinen,et al.  Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. , 2000, Diabetes care.

[32]  L. Schäffer,et al.  Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. , 2000, Diabetes.

[33]  R. Bergman,et al.  Mechanism of protracted metabolic effects of fatty acid acylated insulin, NN304, in dogs: retention of NN304 by albumin , 1999, Diabetologia.

[34]  J. Brange,et al.  The new era of biotech insulin analogues , 1997, Diabetologia.

[35]  J. Whittingham,et al.  Crystal structure of a prolonged-acting insulin with albumin-binding properties. , 1997, Biochemistry.

[36]  J. Eckel,et al.  Growth promoting and metabolic activity of the human insulin analogue [GlyA21,ArgB31,ArgB32]insulin (HOE 901) in muscle cells. , 1997, European journal of pharmacology.

[37]  U. Ribel,et al.  Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. , 1995, The Biochemical journal.

[38]  B H Frank,et al.  Altering the association properties of insulin by amino acid replacement. , 1992, Protein engineering.

[39]  D R Owens,et al.  Monomeric Insulins and Their Experimental and Clinical Implications , 1990, Diabetes Care.

[40]  H. Hagedorn Protamine Insulinate , 1937 .

[41]  A. Fisher,et al.  Crystalline insulin. , 1926, The Biochemical journal.

[42]  J. B. Collip,et al.  Pancreatic Extracts in The Treatment of Diabetes Mellitus , 1922, Diabetes.

[43]  D. Figgitt,et al.  Insulin Glargine , 2012, Drugs.

[44]  D. Mayer,et al.  Proliferative effects of insulin analogues on mammary epithelial cells. , 2008, Archives of physiology and biochemistry.

[45]  A. P. Morrison,et al.  AUTHOR ' S PROOF , 2004 .

[46]  Z. Laron, IGF-1 and insulin as growth hormones. , 2004, Novartis Foundation symposium.