title: Effects on metabolic variables after 12-month treatment with a new once-a-week sustained-release recombinant growth hormone (GH: LB03002) in patients with GH deficiency.
abstract: BACKGROUND
  GH substitution in GH deficiency (GHD) must be subcutaneously administered daily. A new sustained-release formulation of GH (LB03002) has been developed, which has to be injected once a week. As a substudy to the phase III study, we performed this prospective study to evaluate the influence of LB03002 on metabolic variables and hormones.
  
  
  METHODS
  Eleven patients with GHD [four women/seven men, 58 years (29-69 years)] without GH therapy were included in the study. Eight patients were treated with LB03002 for 12 months and three patients received placebo for 6 months followed by LB03002 for 6 months. A 3-h oral glucose tolerance test (OGTT) was performed at study entry and at study end. Additionally, IGF-I, cholesterol, LDL, HDL, triglycerides, leptin, ghrelin, HbA1c and C-peptide were measured. Body composition was evaluated by dual-energy X-ray absorptiometry (DXA), and waist/hip ratio (WHR) and waist/height (WHtR) ratio were measured by tape and scale.
  
  
  RESULTS
  Multiple of upper limit of normal (xULN) of IGF-I (0·23 (0·09-0·4) vs 0·71 (0·4-1·04), P < 0·01), WHR (0·98 (0·86-1·04) vs 1·01 (0·86-1·05), P < 0·05) and ghrelin levels [119·8 ng/l (67·7-266·6) vs 137 ng/l (67-289·5), P < 0·05] were significantly higher, whereas fat mass (FM) [34·7% (20·4-49·2) vs 32·4% (16·7-48·5), P < 0·05] and leptin [11·2 μg/l (3·3-55·7) vs 7·05 μg/l (2·4-54·3), P < 0·05] were significantly lower at study end. Glucose, insulin, HOMA-IR, ISI, HOMA-β, C-peptide and HbA1c during OGTT were not significantly different before and after GH substitution, neither were BMI, WHtR, bone mineral density and lipid variables.
  
  
  CONCLUSIONS
  Substitution with LB03002 showed statistically significant reduction in FM, which reduces leptin levels and increases ghrelin levels but does not seem to influence glucose and lipid metabolism.
authors.affiliation: Department of Internal Medicine (Endocrinology)-Innenstadt, University of Munich, Germany. Josefine.Roemmler@med.uni-muenchen.de
authors.forename: J
authors.initials: J
authors.lastname: Roemmler
authors.forename: A
authors.initials: A
authors.lastname: Gockel
authors.forename: B
authors.initials: B
authors.lastname: Otto
authors.forename: M
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: J
authors.initials: J
authors.lastname: Schopohl
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D001823:Body Composition; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D054439:Ghrelin / Q000378:metabolism*; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D008055:Lipids; D013006:Growth Hormone