Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels

Diabetes Obes Metab. 2016 Jan;18(1):34-9. doi: 10.1111/dom.12571. Epub 2015 Oct 14.


Aims: To evaluate the pharmacokinetics and pharmacodynamics of different doses of glucagon administered subcutaneously (s.c.) at different blood glucose levels.

Methods: This study was an open-label, randomized, three-period, cross-over experiment in 6 patients with type 1 diabetes. During each of the three periods, different blood glucose levels were established in four consecutive steps (8, 6, 4 and 2.8 mmol/l) and glucagon was given at each blood glucose level in doses from 0.11 to 0.44 mg and 0.33, 0.66 and 1 mg at the lowest glucose concentration.

Results: Maximum glucagon concentration and area under the curve increased with increasing glucagon dose. Maximum glucagon concentration was reached after 10-20 min. Glucagon raised blood glucose in a dose-dependent manner at different baseline blood glucose levels. The median glucose excursion ranged from 2.6 to 6.2 mmol/l. Time to maximum glucose concentration was dose-dependent for the glucagon doses at 2.8 mmol/l, with median values from 40 to 80 min.

Conclusions: Glucagon administered s.c. produces a stable pharmacokinetic and pharmacodynamic response at lower doses than the usual rescue dose and across a range of hypo- to hyperglycaemic blood glucose levels. This supports the use of small glucagon doses in the artificial pancreas to correct and prevent hypoglycaemia.

Keywords: glucagon; pharmacodynamics; pharmacokinetics; type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / drug effects*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / pharmacokinetics
  • Glucagon / administration & dosage
  • Glucagon / pharmacokinetics*
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics*
  • Male
  • Middle Aged


  • Blood Glucose
  • Gastrointestinal Agents
  • Hypoglycemic Agents
  • Glucagon