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Diabetes Obes Metab. 2014 May;16(5):388-95. doi: 10.1111/dom.12196. Epub 2013 Sep 12.

PEGylated insulin Lispro, (LY2605541)--a new basal insulin analogue.

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Department of Medicine, University Hospital Llandough, Penarth, UK.


There is a clinical rationale for a basal insulin with a predictable action and low inter- and intra-individual variability coupled with an improved side effect and metabolic profile. Since insulin therapy is anabolic and its initiation is commonly associated with weight gain, an insulin preparation associated with a beneficial weight profile would represent a particularly valuable therapeutic entity. LY2605541, or PEGylated insulin Lispro, has a large hydrodynamic size while still exerting the metabolic effects of insulin. This may reduce absorption and clearance of the compound following subcutaneous administration. A number of preclinical and clinical studies have been constructed to evaluate the utility of this novel insulin. The currently available data from preclinical, phase I and phase II studies suggests LY2605541 has a non-inferior glucose-lowering efficacy compared to insulin glargine in people with type 1 and type 2 diabetes and may afford a weight-loss advantage. Pre-clinical studies indicate that LY2605541 has low mitogenic potency, exerting a preferential hepatic effect on glucose homeostasis. LY2605541 appears to cause elevated transaminases and derangement of lipid profiles. On the basis of these initial observations, LY2605541 requires further extensive clinical evaluation to fully assess its risk/benefit profile in the management in people with diabetes.


diabetes mellitus; insulin analogues; insulin therapy; liver; pharmacodynamics; pharmacokinetics

[Indexed for MEDLINE]

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