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Cited by 429Diabetes Treatment and ManagementPancreatic function and diabetesDiabetes Management and Research

One Week’s Treatment With the Long-Acting Glucagon-Like Peptide 1 Derivative Liraglutide (NN2211) Markedly Improves 24-h Glycemia and α- and β-Cell Function and Reduces Endogenous Glucose Release in Patients with Type 2 Diabetes

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Degn, Kristine B., Juhl, Claus B., Sturis, Jeppe, Jakobsen, Grethe, Brock, Birgitte, Chandramouli, Visvanathan, Rungby, Joergen, Landau, Bernard R. +1 more·2004·Diabetes
DOI 10.2337/diabetes.53.5.1187
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Abstract

Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabetes. We explored the effect of short-term (1 week) treatment with a GLP-1 derivative, liraglutide (NN2211), on 24-h dynamics in glycemia and circulating free fatty acids, islet cell hormone profiles, and gastric emptying during meals using acetaminophen. Furthermore, fasting endogenous glucose release and gluconeogenesis (3-3H-glucose infusion and 2H2O ingestion, respectively) were determined, and aspects of pancreatic islet cell function were elucidated on the subsequent day using homeostasis model assessment and first- and second-phase insulin response during a hyperglycemic clamp (plasma glucose ∼16 mmol/l), and, finally, on top of hyperglycemia, an arginine stimulation test was performed. For accomplishing this, 13 patients with type 2 diabetes were examined in a double-blind, placebo-controlled crossover design. Liraglutide (6 μg/kg) was administered subcutaneously once daily. Liraglutide significantly reduced the 24-h area under the curve for glucose (P = 0.01) and glucagon (P = 0.04), whereas the area under the curve for circulating free fatty acids was unaltered. Twenty-four-hour insulin secretion rates as assessed by deconvolution of serum C-peptide concentrations were unchanged, indicating a relative increase. Gastric emptying was not influenced at the dose of liraglutide used. Fasting endogenous glucose release was decreased (P = 0.04) as a result of a reduced glycogenolysis (P = 0.01), whereas gluconeogenesis was unaltered. First-phase insulin response and the insulin response to an arginine stimulation test with the presence of hyperglycemia were markedly increased (P < 0.001), whereas the proinsulin/insulin ratio fell (P = 0.001). The disposition index (peak insulin concentration after intravenous bolus of glucose multiplied by insulin sensitivity as assessed by homeostasis model assessment) almost doubled during liraglutide treatment (P < 0.01). Both during hyperglycemia per se and after arginine exposure, the glucagon responses were reduced during liraglutide administration (P < 0.01 and P = 0.01). Thus, 1 week’s treatment with a single daily dose of the GLP-1 derivative liraglutide, operating through several different mechanisms including an ameliorated pancreatic islet cell function in individuals with type 2 diabetes, improves glycemic control throughout 24 h of daily living, i.e., prandial and nocturnal periods. This study further emphasizes GLP-1 and its derivatives as a promising novel concept for treatment of type 2 diabetes.

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  • GLP-1 has extrapancreatic actions: suppression of endogenous glucose production/glycogenolysis, glucagon secretion, appetite, delay in gastric emptying, improved β-cell insulin sensitivity and glucose disposal; GIP positively affects lipid and bone metabolism.

    “The extrapancreatic actions of GLP-1 include suppression of endogenous glucose production196/glycogenolysis,197 glucagon secretion,197, 198 appetite,199, 200 a delay in gastric emptying198, 199 and improved β-cell insulin sensitivity199, 201, 202 and glucose disposal,203, 204 whereas GIP positively affects lipid205, 206, 207 and bone metabolism.208, 209, 210, 211”

    From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [197]

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  • Analogs of glucagon-like peptide-1 are associated with improvements in glycemic control.

    “Analogs of glucagon-like peptide-1 are associated with improvements in glycemic control (144 -148).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [148]

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Authors
Degn, K. B., Juhl, C. B., Sturis, J., Jakobsen, G., Brock, B., Chandramouli, V., Rungby, J., Landau, B. R., & Schmitz, O.
Affiliations
  • Aarhus University (DK)
  • Novo Nordisk (Denmark) (DK)
  • Case Western Reserve University (US)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2004-05-01
Volume
53
Issue
5
Pages
1187-1194
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.53.5.1187
OpenAlex
W2102400698
Cited by
427
References
50
Citations by year
2026: 3 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 8 · 2021: 4 · 2020: 10 · 2019: 6 · 2018: 13 · 2017: 7 · 2016: 27 · 2015: 24 · 2014: 27 · 2013: 30 · 2012: 21
FWCI
16.53
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Novo Nordisk
  • Diabetesforeningen
  • National Institutes of Health
  • U.S. Public Health Service (NIH 14507)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
liraglutide, glucagon-like peptide-1, type 2 diabetes, gluconeogenesis, glycogenolysis, insulin secretion, first-phase insulin response, proinsulin/insulin ratio, glucagon, gastric emptying, free fatty acids, disposition index, arginine stimulation test, hyperglycemic clamp
MeSH terms
Liraglutide, Circadian Rhythm, Delayed-Action Preparations, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Administration Schedule, Female, Gastric Emptying, Glucagon, Glucose, Hormones, Humans, Hypoglycemic Agents, Insulin Resistance, Islets of Langerhans, Male, Middle Aged, Cross-Over Studies, Glucagon-Like Peptide 1

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