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Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes.

Publication ,  Journal Article
Ehlers, MR; Klaff, LJ; D'Alessio, DA; Brazg, R; Kay, HD; Harley, RE; Mathisen, AL; Schneider, R
Published in: Horm Metab Res
October 2003

AIMS: To evaluate the safety and efficacy of various doses of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered subcutaneously (s. c.) via bolus injection or continuous infusion to lower fasting serum glucose (FSG) levels in subjects with type 2 diabetes treated by diet, hypoglycemic drugs, or insulin injection. METHODS: rGLP-1 was administered s. c. to 40 type 2 diabetics currently treated by diet, sulfonylurea (SU), metformin, or insulin in a double-blind, placebo-controlled, cross-over trial; preexisting treatments were continued during the study. In the bolus injection protocol, 32 subjects (8 from each of the 4 treatment groups) received 0.0, 0.5, 1.0, and 1.5 nmol rGLP-1/kg per injection (two injections, two hours apart, beginning one hour after the evening meal) in a randomized order on separate days. In the continuous s. c. infusion protocol, 40 subjects received rGLP-1 at 0.0, 1.5, 2.5, 3.5, and 4.5 pmol/kg/min for 10-12 hours overnight starting one hour after the evening meal. Fasting bloods were taken the morning after for glucose, insulin, and glucagon measurements. RESULTS: In the diet, SU, and metformin cohorts, bolus rGLP-1 injections produced modest reductions in mean FSG levels, averaging 17.4 mg/dl (7.3-27.5; 95 % CI) at the highest dose (p < 0.001 vs. placebo). Reductions in FSG levels were greater by continuous infusion at up to 30.3 mg/dl (18.8 - 41.8; 95 % CI; p < 0.001 vs. placebo). The greatest reduction in mean FSG occurred in the SU cohort (up to 43.9 mg/dl, 24.7 - 63.1; 95 % CI; p < 0.001). rGLP-1 infusions resulted in significant increases in fasting plasma insulin and decreases in fasting plasma glucagon levels. There were no serious adverse events; GI-related symptoms were dose-related and more commonly associated with injections. CONCLUSIONS: rGLP-1 (7-36) amide dose-dependently lowered FSG in a broad spectrum of type 2 diabetics when added to their existing treatment. Subcutaneous infusion was more effective than injection, and the combination with SU was more effective than with metformin.

Duke Scholars

Published In

Horm Metab Res

DOI

ISSN

0018-5043

Publication Date

October 2003

Volume

35

Issue

10

Start / End Page

611 / 616

Location

Germany

Related Subject Headings

  • Sulfonylurea Compounds
  • Recombinant Proteins
  • Placebos
  • Peptide Fragments
  • Metformin
  • Insulin
  • Hypoglycemic Agents
  • Humans
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
 

Citation

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Ehlers, M. R., Klaff, L. J., D’Alessio, D. A., Brazg, R., Kay, H. D., Harley, R. E., … Schneider, R. (2003). Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes. Horm Metab Res, 35(10), 611–616. https://doi.org/10.1055/s-2003-43509
Ehlers, M. R., L. J. Klaff, D. A. D’Alessio, R. Brazg, H. D. Kay, R. E. Harley, A. L. Mathisen, and R. Schneider. “Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes.Horm Metab Res 35, no. 10 (October 2003): 611–16. https://doi.org/10.1055/s-2003-43509.
Ehlers MR, Klaff LJ, D’Alessio DA, Brazg R, Kay HD, Harley RE, et al. Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes. Horm Metab Res. 2003 Oct;35(10):611–6.
Ehlers, M. R., et al. “Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes.Horm Metab Res, vol. 35, no. 10, Oct. 2003, pp. 611–16. Pubmed, doi:10.1055/s-2003-43509.
Ehlers MR, Klaff LJ, D’Alessio DA, Brazg R, Kay HD, Harley RE, Mathisen AL, Schneider R. Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes. Horm Metab Res. 2003 Oct;35(10):611–616.
Journal cover image

Published In

Horm Metab Res

DOI

ISSN

0018-5043

Publication Date

October 2003

Volume

35

Issue

10

Start / End Page

611 / 616

Location

Germany

Related Subject Headings

  • Sulfonylurea Compounds
  • Recombinant Proteins
  • Placebos
  • Peptide Fragments
  • Metformin
  • Insulin
  • Hypoglycemic Agents
  • Humans
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1