Diabetologia

, Volume 39, Issue 12, pp 1546–1553

Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7–36 amide]) in patients with NIDDM

  • M. A. Nauck
  • D. Wollschläger
  • J. Werner
  • J. J. Holst
  • C. Ørskov
  • W. Creutzfeldt
  • B. Willms

Summary

Intravenous glucagon-like peptide (GLP)-1 [7–36 amide] can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients. Since this is no form for routine therapeutic administration, effects of subcutaneous GLP-1 at a high dose (1.5 nmol/kg body weight) were examined. Three groups of 8, 9 and 7 patients (61 ± 7, 61 ± 9, 50 ± 11 years; BMI 29.5 ± 2.5, 26.1 ± 2.3, 28.0 ± 4.2 kg/m2; HbA1 c 11.3 ± 1.5, 9.9 ± 1.0, 10.6 ± 0.7 %) were examined: after a single subcutaneous injection of 1.5 nmol/kg GLP [7–36 amide]; after repeated subcutaneous injections (0 and 120 min) in fasting patients; after a single, subcutaneous injection 30 min before a liquid test meal (amino acids 8 %, and sucrose 50 g in 400 ml), all compared with a placebo. Glucose (glucose oxidase), insulin, C-peptide, GLP-1 and glucagon (specific immunoassays) were measured. Gastric emptying was assessed with the indicator-dilution method and phenol red. Repeated measures ANOVA was used for statistical analysis. GLP-1 injection led to a short-lived increment in GLP-1 concentrations (peak at 30–60 min, then return to basal levels after 90–120 min). Each GLP-1 injection stimulated insulin (insulin, C-peptide, p < 0.0001, respectively) and inhibited glucagon secretion (p < 0.0001). In fasting patients the repeated administration of GLP-1 normalized plasma glucose (5.8 ± 0.4 mmol/l after 240 min vs 8.2 ± 0.7 mmol/l after a single dose, p = 0.0065). With the meal, subcutaneous GLP-1 led to a complete cessation of gastric emptying for 30–45 min (p < 0.0001 statistically different from placebo) followed by emptying at a normal rate. As a consequence, integrated incremental glucose responses were reduced by 40 % (p = 0.051). In conclusion, subcutaneous GLP-1 [7–36 amide] has similar effects in NIDDM patients as an intravenous infusion. Preparations with retarded release of GLP-1 would appear more suitable for therapeutic purposes because elevation of GLP-1 concentrations for 4 rather than 2 h (repeated doses) normalized fasting plasma glucose better. In the short term, there appears to be no tachyphylaxis, since insulin stimulation and glucagon suppression were similar upon repeated administrations of GLP-1 [7–36 amide]. It may be easier to influence fasting hyperglycaemia by GLP-1 than to reduce meal-related increments in glycaemia. [Diabetologia (1996) 39: 1546–1553]

Keywords GLP-1 [7 36 amide] incretin insulin glucagon pharmacokinetics. 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • M. A. Nauck
    • 1
  • D. Wollschläger
    • 2
  • J. Werner
    • 2
  • J. J. Holst
    • 3
  • C. Ørskov
    • 3
  • W. Creutzfeldt
    • 4
  • B. Willms
    • 2
  1. 1.Department of Medicine, Ruhr-University Bochum, Knappschafts-Krankenhaus, Bochum, GermanyDE
  2. 2.Fachklinik für Diabetes und Stoffwechselkrankheiten, Bad Lauterberg, GermanyDE
  3. 3.Departments of Anatomy and Physiology, Panum Institute, University of Copenhagen, DenmarkDK
  4. 4.Division of Gastroenterology and Endocrinology, Department of Medicine, Georg-August-University, Göttingen, GermanyDE

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