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Cited by 284Diabetes Treatment and ManagementDiabetes Management and ResearchPancreatic function and diabetes

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-Like Peptide 1 Derivative, in Healthy Male Subjects

Elbrønd, Bodil, Jakobsen, Grethe, Larsen, Søren, Agersø, Henrik, Jensen, Lisbeth Bjerring, Rolan, Paul, Sturis, Jeppe, Hatorp, Vibeke +1 more·2002·Diabetes Care
DOI 10.2337/diacare.25.8.1398
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Abstract

OBJECTIVE—The primary objective of the present study was to investigate the safety, tolerability, and pharmacokinetics of a single dose of NN2211, a long-acting glucagon-like peptide 1 (GLP-1) derivative, in healthy male subjects. The secondary objective was to investigate the pharmacodynamics of NN2211. RESEARCH DESIGN AND METHODS—In a double-blind, randomized dose, escalation, placebo-controlled study, healthy male subjects were enrolled at eight consecutive dose levels (1.25, 2.5, 5.0, 10.0, 12.5, 15.0, 17.5, and 20.0 μg/kg) with eight subjects per dose level at a 3:1 active:placebo randomization. After subcutaneous dosing with NN2211, 48-h pharmacokinetic, and 24-h glucose, insulin and glucagon profiles were assessed. In addition, three subjects at each dose level were randomly assigned (one placebo/two active) to an intravenous glucose tolerance test (IVGTT) 9 h after the dose (corresponding to the time to maximal plasma concentration of NN2211). RESULTS—After subcutaneous administration, the half-life of NN2211 was found to be 11–15 h. Overall, although there were no statistically significant differences compared with placebo in the area under the curve (0–9 h for insulin or glucagon), there was a borderline- significant lowering of glucose levels (P = 0.066). During the IVGTT, there was a statistically significant increase in insulin secretion (P = 0.0002), but there was no significant effect on glucagon levels. Although no significant effect was observed on glucose levels during the IVGTT, there was a dose-dependent increase in the glucose disappearance constant. Whereas no serious adverse events were observed, there was a higher incidence of adverse events after active treatment compared with placebo treatment (notably headache, dizziness, nausea, and vomiting). CONCLUSIONS—This study provides evidence that NN2211 has a pharmacokinetic profile consistent with once-daily dosing in humans.

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  • The longer half-life of AMG 133 (mean t1/2 ~21 d) along with the duration of weight loss after single and repeat dosing enabled less-frequent dosing at every 4 weeks in the MAD study compared to other GLP-1 agonists and dual GIPR/GLP-1 agonists, which require daily or weekly dosing.

    “The longer half-life of AMG 133 (mean t1/2 ~ 21 d) along with the duration of weight loss seen after a single dose as well as repeat dosing of AMG 133 enabled less-frequent dosing at every 4 weeks in the MAD study compared to other GLP-1 agonists and dual GIPR/GLP-1 agonists, which require either daily or weekly dosing based on the shorter half-lives of these agents20,42,43.”

    From A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (2024) · cites this paper as [42]

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Authors
Elbrønd, B., Jakobsen, G., Larsen, S., Agersø, H., Jensen, L. B., Rolan, P., Sturis, J., Hatorp, V., & Zdravkovic, M.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Medeval Ltd., Manchester Science Park, Manchester, U.K
ORCID
Sturis, Jeppe
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2002-08-01
Volume
25
Issue
8
Pages
1398-1404
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/diacare.25.8.1398
OpenAlex
W2063715420
Cited by
279
References
26
Citations by year
2026: 1 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 7 · 2017: 8 · 2016: 14 · 2015: 15 · 2014: 9 · 2013: 12 · 2012: 13
FWCI
6.35
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders
American Diabetes Association
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
long-acting GLP-1 receptor agonists, pharmacokinetics, pharmacodynamics, safety and tolerability, subcutaneous administration, insulin secretion, glucagon, glucose metabolism, once-daily dosing, dose escalation, adverse events
MeSH terms
Liraglutide, Adolescent, Adult, Blood Glucose, Double-Blind Method, Glucagon, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Glucagon-Like Peptide 1

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