Diabetologia

, Volume 44, Issue 11, pp 2018–2024

Effects of a novel glucagon receptor antagonist (Bay 27–9955) on glucagon-stimulated glucose production in humans

  • K. F. Petersen
  • J. T. Sullivan

DOI: 10.1007/s001250100006

Cite this article as:
Petersen, K. & Sullivan, J. Diabetologia (2001) 44: 2018. doi:10.1007/s001250100006

Abstract.

Aims/hypothesis:

To study the effects of a specific glucagon receptor antagonist (Bay 27–9955), on plasma glucose concentrations and rates of glucose production in response to hyperglucagonaemia in humans.

Methods:

The study was conducted as a two-dose [Low Dose Bay 27–9955 70 mg, (n = 6), High Dose Bay 27–9955 200 mg, (n = 8)], double blind, placebo controlled, crossover study. Basal glucose production was measured after an overnight fast with [6,6-2H]. At 0 min Bay 27–9955 or placebo was administeredand at 120 min an infusion of somatostatin [0.1 μg · (kg · min)–1], insulin [24 pmol · (m2· min)–1] and glucagon [3 ng · (kg · min)–1] was initiated.

Results:

Basal plasma glucose concentrations were about 5 mmol/l and basal rates of glucose production were about 13 μmol · (kg · min)–1. During the hyperglucagonaemic period, plasma glucagon concentrations doubled to 100 pg/ml, plasma glucose concentration increased by 75 % to a peak of about 10 mmol/l and glucose production doubled to about 23 μmol · (kg · min)–1 (p < 0.0001 vs basal). In the High Dose Group these effects of glucagon were markedly blunted, plasma glucose concentrations were 7.6 ± 1.1 mmol/l (p = 0.012 vs placebo) and rates of glucose production increased minimally to 15.3 ± 1.9 μmol · (kg-min)–1 (p < 0.0003 vs placebo]. In the Low Dose Group, there was a proportional decrease in the effects of Bay 27–9955 on these parameters.

Conclusion/interpretation:

Bay 27–9955 is an effective and safe glucagon antagonist in humans. Given the potentially important role of glucagon in increasing glucose production and gluconeogenesis in patients with Type II (non-insulin-dependent) diabetes mellitus this agent could represent an innovative class of therapeutic agents for the disease. [Diabetologia (2001) 44: 2018–2024]

Keywords Glucagon, glucagon antagonist, glucose production, diabetes. 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • K. F. Petersen
    • 1
  • J. T. Sullivan
    • 2
  1. 1.Yale University School of Medicine, Department of Internal Medicine, New Haven, Connecticut, USAUS
  2. 2.Bayer Pharmaceuticals, West Haven, CT, USAUS