We thank Professor Home for his interest (1) in our publication on a novel basal insulin analog, LY2605541 (2).
Total, LDL, and HDL cholesterol levels along with triglyceride levels (or lipid profiles) were measured as noted in the last paragraph on page 2144 (2). Whereas the serum triglyceride measurements for the LY2605541-treated patients did not differ from baseline but were higher compared with insulin glargine–treated patients, the total, HDL, and LDL cholesterol did not differ from baseline for the LY2605541-treated patients and did not differ from those treated with insulin glargine. In contrast, in the recently published type 1 diabetes study (3), LY2605541-treated patients demonstrated a modest increase in triglycerides and LDL cholesterol compared with baseline and to insulin glargine-treated patients, whereas the HDL cholesterol with LY2605541 decreased from baseline and compared with insulin glargine. As these findings were first noted in these exploratory phase 2 studies, the phase 3 studies will measure routine lipids and hepatic transaminase levels at frequent intervals to characterize the chronology of these changes. Additionally, in a subset of patients, these studies will measure hepatic fat content by magnetic resonance imaging, plasma lipoprotein subclass particle concentration (nmol/L), and particle size measured by nuclear magnetic resonance, total cholesterol efflux capacity, free fatty acids, cholesterylester transfer protein activity and mass, adiponectin, and apolipoproteins (Apo-A1, Apo-A2, Apo-B100, and Apo-CIII). Although high-sensitivity C-reactive protein would provide some information regarding inflammation, the determination of hepatic fat content was considered to be a fundamental investigation. The subsequent effects on insulin sensitivity along with determining inflammation were considered to be secondary. Lastly, because these patients were treated with exogenous insulin prestudy, and circulating levels of LY2605541 (similar to insulin detemir) are very different than that of human insulin, we question the validity of the homeostasis model assessment calculations under these circumstances.
Acknowledgments
R.M.B. has served on scientific advisory panels for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer HealthCare, Eli Lilly and Company, Hygieia, Johnson & Johnson, Roche Pharmaceuticals, Sanofi, and Valeritas; has served as a consultant to Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer HealthCare, Boehringer Ingelheim Pharmaceuticals, Calibra Medical, Eli Lilly and Company, Halozyme Therapeutics, Helmsley Trust, Hygieia, Johnson & Johnson, Medtronic, ResMed, Roche Pharmaceuticals, Sanofi, Takeda Pharmaceutical Company, Valeritas, and Becton, Dickinson and Company; has received research support from Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer HealthCare, Boehringer Ingelheim Pharmaceuticals, Calibra Medical, Dexcom, Eli Lilly and Company, Halozyme Therapeutics, Helmsley Trust, Hygieia, Intarcia Therapeutics, Johnson & Johnson, MannKind Corporation, Medtronic, National Institutes of Health, ResMed, Roche Pharmaceuticals, Sanofi, Takeda Pharmaceutical Company, and Becton, Dickinson and Company; and holds stock in Merck & Co. J.R. has served on scientific advisory panels for Roche Pharmaceuticals, Sanofi, Novo Nordisk, Eli Lilly and Company, MannKind Corporation, GlaxoSmithKline, Takeda Pharmaceutical Company, Daiichi-Sankyo, Johnson & Johnson, Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Lexicon Pharmaceuticals; has served as a consultant to Roche Pharmaceuticals, Sanofi, Novo Nordisk, Eli Lilly and Company, MannKind Corporation, GlaxoSmithKline, Takeda Pharmaceutical Company, Daiichi-Sankyo, Johnson & Johnson, Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, and Lexicon Pharmaceuticals; and has received research support from Pfizer, Sanofi, Novo Nordisk, Roche Pharmaceuticals, Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Takeda Pharmaceutical Company, Novartis Pharmaceuticals Corporation, AstraZeneca LP, Amylin Pharmaceuticals, Johnson & Johnson, Daiichi-Sankyo, MannKind Corporation, Lexicon Pharmaceuticals, and Boehringer Ingelheim Pharmaceuticals. R.F.A. has been a consultant to Novo Nordisk and Sanofi; has received research support from Eli Lilly and Company, Sanofi, Novo Nordisk, Novartis Pharmaceuticals Corporation, AstraZeneca LP, and Reata Pharmaceuticals; and has participated in Speaker’s Bureaus for Amylin Pharmaceuticals and Eli Lilly and Company. M.J.P., Y.Q., and S.J.J. are employees of and hold stock in Eli Lilly and Company. D.C.H. is a retired employee of Eli Lilly and Company and holds stock in Eli Lilly and Company. V.P.S. is a past employee and is currently a stock holder of Eli Lilly and Company. No other potential conflicts of interest relevant to this article were reported.