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

J. Roemmler; A. Gockel; B. Otto; M. Bidlingmaier; J. Schopohl

Disclosures

Clin Endocrinol. 2012;76(1):88-95. 

In This Article

Summary and Introduction

Summary

Introduction 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.
Conclusion 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.

Introduction

A new once-a-week growth hormone (GH) formulation, LB03002, is being developed by LG Life Sciences, Ltd, Seoul, Korea. It is a sustained-release GH which is formulated as a sterile microparticular powder. It consists of GH incorporated in sodium hyaluronate dispersed in medium-chain triglyceride for reconstitution to a suspension. The active ingredient is recombinant somatrophin, marketed by LG Life Sciences as a daily formulation, Eutropin®. The pharmacokinetics and pharmacodynamics of LB03002 have been tested in adult patients with growth hormone deficiency (GHD).[1] It could be shown that IGF-I levels stay within a target range for at least 5 days without safety concerns. Weekly administration of LB03002 induces IGF-I levels of sufficient height and duration to promote the metabolic effects of GH substitution. A Phase III, double-blind, randomized, placebo-controlled, parallel-group, multicentre study was performed to assess the efficacy and safety of LB03002 administered weekly in adults with GHD. Our centre, the Department of Internal Medicine of the LMU Munich, participated in the aforementioned clinical trials has provided us the opportunity to treat 11 GHD adult patients with LB03002 for 12 months.

GH is a pituitary hormone with many metabolic effects. Patients with GHD often have an impairment of glucose metabolism with increased insulin resistance (IR) and reduced β-cell function[2,3] and increased fat mass (FM).[4,5] In addition, cardiovascular mortality is increased in GHD.[6,7] The metabolic hormones leptin and ghrelin are also affected; leptin levels are reported to be either increased[8] or similar[9] compared with healthy controls, whereas ghrelin levels seem to be either lower[10] or unchanged.[4] GH substitution with daily subcutaneous injections has been shown to influence the metabolic system by antagonizing insulin action[11] and changing glucose homoeostasis,[5,12,13] improving lipid metabolism,[14,15] reducing FM,[13,16] increasing lean body mass[17] and mineralizing bone mass.[18,19] Leptin levels often decrease and ghrelin levels increase after GH substitution in GHD,[4,8,20] but some studies could not find a significant change in leptin and ghrelin levels after GH substitution.[8,21,22] So far, experience with only one other long-acting GH (Nutropin Depot, Ipsen Pharma GmbH, France) in adult GHD was published.[23,24]

We conducted the following study to assess the influence of the sustained-release GH formulation LB03002 on glucose and lipid variables and effects of the metabolic hormones such as leptin and ghrelin on body composition in 11 adult patients with GHD.

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