title: Different effects of basal insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes.
abstract: To compare effects of basal insulin peglispro (BIL), a hepatopreferential insulin, to insulin glargine (glargine) on aminotransferases and liver fat content (LFC) in patients with type 1 and type 2 diabetes (T1D, T2D).
  
  
  
  Data from two Phase 2 and five Phase 3 randomized trials comparing BIL and glargine in 1709 T1D and 3662 T2D patients were integrated for analysis of liver laboratory tests. LFC, measured by magnetic resonance imaging (MRI) at baseline, 26 and 52 weeks, was analyzed in 182 T1D patients, 176 insulin-naïve T2D patients and 163 T2D patients previously treated with basal insulin.
  
  
  
  Alanine aminotransferase (ALT) increased in patients treated with BIL, was higher than in glargine-treated patients at 4-78 weeks (difference at 52 weeks in both T1D and T2D: 7 international units/litre (IU/L), P < .001), and decreased after discontinuation of BIL. More BIL patients had ALT ≥3× upper limit of normal (ULN) than glargine. No patient had ALT ≥3× ULN with bilirubin ≥2× ULN that was considered causally related to BIL. In insulin-naїve T2D patients, LFC decreased with glargine but was unchanged with BIL. In T1D and T2D patients previously treated with basal insulin, LFC was unchanged with glargine but increased with BIL. In all three populations, LFC was higher after treatment with BIL vs glargine (difference at 52 weeks: 2.2% to 5.3%, all P < .01).
  
  
  
  Compared to glargine, patients treated with BIL had higher ALT and LFC at 52-78 weeks. No severe drug-induced liver injury was apparent with BIL treatment for up to 78 weeks.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Cusi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hoogwerf
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Chang
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Jacober
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Bue-Valleskey
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Higdon
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.|Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Bastyr
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Haupt
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA. hartman@lilly.com.
authors.forename: M L
authors.initials: ML
authors.lastname: Hartman
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000627:therapeutic use*; D061268:Insulin Lispro / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077205:Pioglitazone; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro; D008687:Metformin; D000077205:Pioglitazone; D011092:Polyethylene Glycols; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014280:Triglycerides; C000621851:basal insulin peglispro; C517652:hemoglobin A1c protein, human
keywords: basal insulin; fatty liver; liver; randomized trial; type 1 diabetes; type 2 diabetes