title: Basal insulin analogs: from pathophysiology to therapy. What we see, know, and try to comprehend?
abstract: During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable.
authors.affiliation: Institute of Clinical Research, Laboratory of Human Nutrition, 641, avenue du Doyen-Giraud, 34093 Montpellier cedex 5, France. Electronic address: louis.monnier@inserm.fr.
authors.forename: L
authors.initials: L
authors.lastname: Monnier
authors.forename: C
authors.initials: C
authors.lastname: Colette
authors.forename: D
authors.initials: D
authors.lastname: Owens
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives*; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000627:therapeutic use
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting; C571886:insulin degludec
keywords: Analogues prolongés de l’insuline; Basal insulin analogs; Pathophysiology; Physiopathologie