Basal insulin peglispro: Overview of a novel long-acting insulin with reduced peripheral effect resulting in a hepato-preferential action

Diabetes, Obesity and Metabolism

Volumn 18, Issue , 2016, Pages 3-16

  Jacober, Scott J ^a   Prince, M J ^a   Beals, J M ^a   Hartman, M L ^a   Qu, Y ^a   Linnebjerg, H ^a   Garhyan, P ^a   Haupt, A ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

basal insulin; drug development; drug mechanism; hypoglycaemia; insulin therapy

Indexed keywords

ALANINE AMINOTRANSFERASE; FAT; GLUCOSE; HEMOGLOBIN A1C; INSULIN GLARGINE; INSULIN PEGLISPRO; ISOPHANE INSULIN; LONG ACTING INSULIN; TRIACYLGLYCEROL; ANTIDIABETIC AGENT; BASAL INSULIN PEGLISPRO; GLUCOSE BLOOD LEVEL; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN; INSULIN; INSULIN LISPRO; MACROGOL DERIVATIVE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTHRALGIA; ARTICLE; BACKACHE; BRONCHITIS; CARDIOVASCULAR DISEASE; COUGHING; DIARRHEA; DISEASE SEVERITY; DOSAGE SCHEDULE COMPARISON; DRUG EFFECT; DRUG SAFETY; FEVER; GASTROENTERITIS; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HEPATOPREFERENTIAL ACTION; HUMAN; HYPERTENSION; HYPOGLYCEMIA; IMMUNOGENICITY; INFLUENZA; INJECTION SITE REACTION; INSULIN DEPENDENT DIABETES MELLITUS; LIPOHYPERTROPHY; LIVER LEVEL; NAUSEA; NOCTURNAL HYPOGLYCEMIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OROPHARYNX PAIN; PAIN; PHARYNGITIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEPTOR BINDING; RHINOPHARYNGITIS; SIDE EFFECT; SINUSITIS; TOXIC HEPATITIS; TRIACYLGLYCEROL BLOOD LEVEL; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VIRAL GASTROENTERITIS; VOMITING; WEIGHT GAIN; ANALOGS AND DERIVATIVES; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; LIVER; METABOLISM; TREATMENT OUTCOME; WEIGHT REDUCTION;

ALANINE TRANSAMINASE; BLOOD GLUCOSE; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN; INSULIN GLARGINE; INSULIN LISPRO; INSULIN, ISOPHANE; LIVER; POLYETHYLENE GLYCOLS; TREATMENT OUTCOME; TRIGLYCERIDES; WEIGHT LOSS;

EID: 84990176917     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12744     Document Type: Article

References (65)

1. Hirsch IB, Skyler JS. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al., eds., The Management of Type 1 Diabetes. South Dartmouth, MA: Endotext; 2013.
2. Hirsch IB. Intensifying insulin therapy in patients with type 2 diabetes mellitus. Am J Med. 2005;118(Suppl 5A):21S–26S.
3. Hirsch IB. Insulin analogues. N Engl J Med. 2005;352:174–183.
4. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003;289:2254–2264.
5. Gregory JM, Kraft G, Scott MF, et al. Insulin delivery into the peripheral circulation: a key contributor to hypoglycemia in type 1 diabetes. Diabetes. 2015;64:3439–3451.
6. Edgerton DS, Lautz M, Scott M, et al. Insulin's direct effects on the liver dominate the control of hepatic glucose production. J Clin Invest. 2006;116:521–527.
7. Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis SA. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract. 2011;93(Suppl 1):S52–S59.
8. Owens R, Hansen R, Kahl S, et al. In vitro and in vivo characterization of basal insulin peglispro: a novel insulin analog. J Pharmacol Exp Ther. 2016;357:459–465.
9. Kiselyov VV, Ding L, Wu GY, Moyers J. Analysis of basal insulin peglispro (BIL) binding kinetics with the use of a harmonic oscillator insulin receptor binding model. Diabetes. 2015;64:A264–A265.
10. Kiselyov VV, Moyers JS, Volk CB, et al. Binding kinetics, internalisation and localisation of long-acting basal insulin peglispro (BIL) and insulin receptor in cells. Diabetologia. 2014;57:S398.
11. Sinha VP, Howey DC, Choi SL, Mace KF, Heise T. Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2014;16:344–350.
12. Garhyan P, Choi SL, Smith LaBell E, Knadler MP, Prince MJ. Clinical pharmacokinetics (PK) and renal elimination of basal insulin peglispro (BIL) and its polyethylene glycol (PEG)-containing products. Diabetes. 2015;64:LB22.
13. Knadler MP, Ellis BB, Brown-Augsburger PL, Murphy AT, Martin JA, Wroblewski VJ. Disposition of basal insulin peglispro compared with 20-kDa polyethylene glycol in rats following a single intravenous or subcutaneous dose. Drug Metab Dispos. 2015;43:1477–1483.
14. Sinha VP, Choi SL, Soon DK, et al. Single-dose pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 in healthy subjects. J Clin Pharmacol. 2014;54:792–799.
15. Knadler MP, Nguyen T-H, Campanale KM, De Veer MJ, Beals JM, Porter CJH. Lymphatic absorption of basal insulin peglispro (BIL) in sheep. Diabetes. 2015;64:A262.
16. Heise T, Meneghini LF. Insulin stacking versus therapeutic accumulation: understanding the differences. Endocr Pract. 2014;20:75–83.
17. Lam ECQ, Garhyan P, Linnebjerg H, et al. Reduced intra-subject variability of basal insulin peglispro (BIL) compared with insulin glargine (GL) in patients with type 1 diabetes mellitus (T1DM). Diabetes. 2015;64:A25.
18. Morrow LA, Hompesch M, Jacober SJ, Siak L, Qu Y, Sinha VP. Glucodynamics of long-acting basal insulin peglispro (BIL) compared with insulin glargine at steady state in subjects with type 1 diabetes: substudy of a randomized crossover trial. Diabetes Obes Metab. 2016;18:1064–1070.
19. Shah VN, Moser EG, Blau A, Dhingra M, Garg SK. The future of basal insulin. Diabetes Technol Ther. 2013;15:727–732.
20. Moore MC, Smith MS, Sinha VP, et al. Novel PEGylated basal insulin LY2605541 has a preferential hepatic effect on glucose metabolism. Diabetes. 2014;63:494–504.
21. Henry RR, Mudaliar S, Ciaraldi TP, et al. Basal insulin peglispro demonstrates preferential hepatic versus peripheral action relative to insulin glargine in healthy subjects. Diabetes Care. 2014;37:2609–2615.
22. Mudaliar S, Henry RR, Ciaraldi TP, et al. Basal insulin peglispro (BIL) demonstrates hepato-preferential action vs insulin glargine (GL) in patients with type 1 diabetes mellitus. Diabetologia. 2015;58:S1.
23. Sonksen PH, Tompkins CV, Srivastava MC, Nabarro JD. A comparative study on the metabolism of human insulin and porcine proinsulin in man. Clin Sci Mol Med. 1973;45:633–654.
24. Glauber HS, Henry RR, Wallace P, et al. The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N Engl J Med. 1987;316:443–449.
25. Shojaee-Moradie F, Jackson NC, Boroujerdi M, Brandenburg D, Sonksen PH, Jones RH. Demonstration of a relatively hepatoselective effect of covalent insulin dimers on glucose metabolism in dogs. Diabetologia. 1995;38:1007–1013.
26. Shojaee-Moradie F, Powrie JK, Sundermann E, et al. Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans. Diabetes Care. 2000;23:1124–1129.
27. Herring R, Knight R, Shojaee-Moradie F, et al. Effect of subcutaneous insulin detemir on glucose flux, lipolysis and electroencephalography in type 1 diabetes. Diabetes Obes Metab. 2015;17:1100–1103.
28. Smeeton F, Shojaee Moradie F, Jones RH, et al. Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes. Diabetologia. 2009;52:2317–2323.
29. McLennan DN, Porter CJ, Charman SA. Subcutaneous drug delivery and the role of the lymphatics. Drug Discov Today Technol. 2005;2:89–96.
30. Charman SA, McLennan DN, Edwards GA, Porter CJ. Lymphatic absorption is a significant contributor to the subcutaneous bioavailability of insulin in a sheep model. Pharm Res. 2001;18:1620–1626.
31. Komarova Y, Malik AB. Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu Rev Physiol. 2010;72:463–493.
32. Yuan SY, Rigor RR. Regulation of Endothelial Barrier Function San Rafael, CA: Morgan & Claypool Life Sciences; 2011:39–55.
33. Hansen RJ, Cutler GB, Vick A, et al. LY2605541: leveraging hydrodynamic size to develop a novel basal insulin. Diabetes. 2012;61:A228.
34. Linnebjerg H, Choi S, ECQ L, Mace K, Hodgson T, Sinha V. Pharmacokinetics of the long-acting basal insulin LY2605541 in subjects with varying degrees of renal function. Clin Pharmacol Drug Dev. 2016;5:216–224.
35. Bergenstal RM, Rosenstock J, Arakaki RF, et al. A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes. Diabetes Care. 2012;35:2140–2147.
36. Rosenstock J, Bergenstal RM, Blevins TC, et al. Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: a randomized, crossover study. Diabetes Care. 2013;36:522–528.
37. Jacober SJ, Rosenstock J, Bergenstal RM, Prince MJ, Qu Y, Beals JM. Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM. Diabetes Obes Metab. 2014;16:351–356.
38. Garg S, Dreyer M, Jinnouchi H, et al. A randomized clinical trial comparing basal insulin peglispro versus and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1 study. Diabetes Obes Metab. 2016;18(S2):25–33.
39. Bergenstal RM, Lunt H, Franek E, et al. A randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3. Diabetes Obes Metab. 2016;18:1080–1087.
40. Blevins T, Pieber TR, Colon Vega G, Zhang S, Bastyr E Jr, Chang AM. A randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 2 diabetes: IMAGINE 4. Diabetes Obes Metab. 2016;18:1071–1079.
41. Buse JB, Rodbard HW, Trescoli Serrano C, et al. A randomized clinical trial comparing basal insulin peglispro and insulin glargine in patients with type 2 diabetes mellitus previously treated with basal insulin: IMAGINE 5. Diabetes Care. 2016;39:92–100.
42. Davies MJ, Russell-Jones D, Selam JL, et al. Double-blind comparison of basal insulin peglispro and insulin glargine in insulin-naïve patients with type 2 diabetes: the IMAGINE 2 clinical trial. Diabetes Obes Metab. 2016;18:1054–1063.
43. Grunberger G, Chen L, Rodríguez A, Tinahones FJ, Jacober SJ, Bue-Valleskey J. A randomized clinical trial of basal insulin peglispro versus NPH in insulin-naive patients with type 2 diabetes: IMAGINE 6. Diabetes Obes Metab. 2016;18(S2):34–42.
44. Garg S, Selam JL, Bhargava A, et al. Similar HbA1c reduction and hypoglycaemia with variable- vs fixed-time dose of basal insulin peglispro (BIL) in type 1 diabetes: IMAGINE 7 study. Diabetes Obes Metab. 2016;18(S2):43–49.
45. Bastyr EJ III, Zhang S, Mou J, Hackett AP, Raymond SA, Chang AM. Performance of an electronic diary system for intensive insulin management in global diabetes clinical trials. Diabetes Technol Ther. 2015;17:571–579.
46. Rosenstock J, Marre M, Qu Y, et al. Reduced nocturnal hypoglycemia with basal insulin peglispro compared to insulin glargine: pooled analyses of 5 randomized controlled trials. Diabetes Obes Metab. 2016;18:1092–1096.
47. Heise T, Kapitza C, Nosek L, et al. Similar counter-regulatory hormone responses to hypoglycaemia with basal insulin peglispro (BIL) versus insulin glargine (GL) in type 1 diabetes. Diabetologia. 2015;58:S466.
48. Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes – causes, effects and coping strategies. Diabetes Obes Metab. 2007;9:799–812.
49. Ben Ammar I, Ksouri H, Trabelsi N, et al. Generalized allergy due to zinc in insulin treated with zinc-free insulin. Acta Diabetol. 2012;49:239–241.
50. Castera V, Dutour-Meyer A, Koeppel M, Petitjean C, Darmon P. Systemic allergy to human insulin and its rapid and long acting analogs: successful treatment by continuous subcutaneous insulin lispro infusion. Diabetes Metab. 2005;31:391–400.
51. Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104:106–110.
52. Raile K, Noelle V, Landgraf R, Schwarz HP. Insulin antibodies are associated with lipoatrophy but also with lipohypertrophy in children and adolescents with type 1 diabetes. Exp Clin Endocrinol Diabetes. 2001;109:393–396.
53. Omar MA, El-Kafoury AA, El-Araby RI. Lipohypertrophy in children and adolescents with type 1 diabetes and the associated factors. BMC Res Notes. 2011;4:290.
54. Blanco M, Hernandez MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39:445–453.
55. Al Ajlouni M, Abujbara M, Batieha A, Ajlouni K. Prevalence of lipohypertrophy and associated risk factors in insulin-treated patients with type 2 diabetes mellitus. Int J Endocrinol Metab. 2015;13:e20776.
56. Ginsberg H, Cariou B, Orchard T, et al. Lipid changes during basal insulin peglispro, insulin glargine, or NPH treatment in 6 IMAGINE trials. Diabetes Obes Metab. 2016;18:1088–1091.
57. Ginsberg H, Cariou B, Orchard TJ, et al. Lipid changes during 26-wk treatment with the novel basal insulin peglispro (BIL) vs. insulin glargine (GL) or insulin NPH in 6 IMAGINE trials. Diabetes. 2015;64:A251.
58. Hoogwerf BJ, Lincoff AM, Rodriguez A, Chen L, Qu Y. Major adverse cardiovascular events with basal insulin peglispro versus comparator insulins in patients with type 1 or type 2 diabetes: a meta-analysis. Cardiovasc Diabetol. 2016;15:78.
59. Cusi K, Sanyal A, Zhang S, et al. Different effects of insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes. Diabetes Obes Metab. 2016;18(S2):50–58.
60. Clinical Evaluation. U.S.Guidance for Industry: Drug-Induced Liver Injury: Premarketing Department of Health and Human Services, Food and Drug Administration, 2009:8.
61. Regev A. How to avoid being surprised by hepatotoxicity at the final stages of drug development and approval. Clin Liver Dis. 2013;17:749–767, xi.
62. Juurinen L, Tiikkainen M, Hakkinen AM, Hakkarainen A, Yki-Jarvinen H. Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292:E829–E835.
63. Lingvay I, Raskin P, Szczepaniak LS. Effect of insulin-metformin combination on hepatic steatosis in patients with type 2 diabetes. J Diabetes Complications. 2007;21:137–142.
64. Tang A, Rabasa-Lhoret R, Castel H, et al. Effects of insulin glargine and liraglutide therapy on liver fat as measured by magnetic resonance in patients with type 2 diabetes: a randomized trial. Diabetes Care. 2015;38:1339–1346.
65. Lomonaco R, Bril F, Portillo-Sanchez P, et al. Metabolic impact of nonalcoholic steatohepatitis in obese patients with type 2 diabetes. Diabetes Care. 2016;39:632–638.