Evidence mapPaperPMID 9525985Full record

Trial reportThe Journal of clinical investigation1998

Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans.

J Schirra, K Sturm, P Leicht, R Arnold, B Göke, M Katschinski

4 registry-linked trialsOpen access · greenAbstract readClinical TrialRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07224334 phase1recruitingstarted 2025, after this paper: background citation

Alpha to Beta Cell Communication in Health and Disease

Ran2025Enrolled30Registered outcomes3Posted comparisons0ConditionsDiabetes (DM)Armsdexamethasone, Exendin-9 is a 30 amino acid peptide that is an established competitive antagonist of the GLP-1 receptor. Subjects will receive exendin-9 by intravenous infusion at a rate of 600 pmol/kg/min
Open the trial in the graph
NCT00393445 phase1completednot on this mapstarted 2006, after this paper: background citation

Effect of GLP-1 on Glucose Metabolism in Healthy Subjects and Patients With T2DM. Part 1: A Pilot Study to Assess the Efficacy of Exendin(9-39)Amide as a GLP-1 Receptor Antagonist in Healthy Subjects

TypeinterventionalSponsorLudwig-Maximilians - University of MunichRan2006 to 2007Enrolled6ConditionsHyperglycemiaArmsGLP-1 control, GLP-1 and Exendin(9-39) 300, saline control, GLP-1 and Exendin(9-39) 600, GLP-1 and Exendin(9-39) 900
NCT00468091 phase1completednot on this mapstarted 1999, after this paper: background citation

Regulation of Antro-pyloro-duodenal and Proximal Gastric Motility by GLP-1: Involvement of Cholinergic Pathways

TypeinterventionalSponsorLudwig-Maximilians - University of MunichRan1999 to 2000Enrolled10ConditionsDigestive Physiology, Gastrointestinal Motility, Gastrointestinal Hormones, Glucagon-like Peptide 1Armsexendin(9-39)amide, atropine
NCT00551590 phase1completednot on this mapstarted 2007, after this paper: background citation

A Randomized, Placebo-Controlled, 4-period, Crossover Study to Assess the Impact of MK-0431 (Sitagliptin) on Incretin Effect and the Role of Specific Incretin Hormones in Patients With Type 2 Diabetes Mellitus

TypeinterventionalSponsorLudwig-Maximilians - University of MunichRan2007 to 2011Enrolled24ConditionsType 2 Diabetes MellitusArmsPlacebo tablet, Sitagliptin tablet, Saline infusion, Exendin(9-39) infusion
3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 266 citations in OpenAlex.

  1. Trial
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  5. GIP(3-30)NHDiabetologia · 2018
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  14. Review
  15. Advances in GLP-1 receptor agonists for pain treatment and their future potential.The journal of headache and pain · 2025 · on this map
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

J SchirraClinical Research Unit for Gastrointestinal Endocrinology and Department of Gastroenterology and Endocrinology, Philipps University, 35033 Marburg, Germany. schirra@mailer.uni-marburg.de
K Sturm
P Leicht
R Arnold
B Göke
M Katschinski
Philipps University of Marburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The gastrointestinal hormone, glucagon-like peptide-1(7-36)amide (GLP-1) is released after a meal. The potency of synthetic GLP-1 in stimulating insulin secretion and in inhibiting glucagon secretion indicates the putative physiological function of GLP-1. In vitro, the nonmammalian peptide, exendin(9-39)amide [ex(9-39)NH2], is a specific and competitive antagonist of GLP-1. This in vivo study examined the efficacy of ex(9-39)NH2 as an antagonist of exogenous GLP-1 and the physiological role of endogenous GLP-1. Six healthy volunteers underwent 10 experiments in random order. In each experiment, a 30-min period of euglycemia was followed by an intravenous infusion of glucose for 150 min that established a stable hyperglycemia of 8 mmol/liter. There was a concomitant intravenous infusion of one of the following: (1) saline, (2) GLP-1 (for 60 min at 0.3 pmol . kg-1 . min-1 that established physiological postprandial plasma levels, and for another 60 min at 0.9 pmol . kg-1 . min-1 to induce supraphysiological plasma levels), (3-5) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + GLP-1, (6-8) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + saline, (9 and 10) GIP (glucose-dependent insulinotropic peptide; for 60 min at 0.8 pmol . kg-1 . min-1, with saline or ex(9-39)NH2 at 300 pmol . kg-1 . min-1). Each volunteer received each of these concomitant infusions on separate days. ex(9-39)NH2 dose-dependently reduced the insulinotropic action of GLP-1 with the inhibitory effect declining with increasing doses of GLP-1. ex(9-39)NH2 at 300 pmol . kg-1 . min-1 blocked the insulinotropic effect of physiological doses of GLP-1 and completely antagonized the glucagonostatic effect at both doses of GLP-1. Given alone, this load of ex(9-39)NH2 increased plasma glucagon levels during euglycemia and hyperglycemia. It had no effect on plasma levels of insulin during euglycemia but decreased plasma insulin during hyperglycemia. ex(9-39)NH2 did not alter GIP-stimulated insulin secretion. These data indicate that in humans, ex(9-39)NH2 is a potent GLP-1 antagonist without any agonistic properties. The pancreatic A cell is under a tonic inhibitory control of GLP-1. At hyperglycemia, the B cell is under a tonic stimulatory control of GLP-1.

Indexed as

AdultC-PeptideGlucagonGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucoseHumansInsulinMalePeptide FragmentsProtein PrecursorsReceptors, GlucagonTime FactorsC-Peptideexendin (9-39)GLP1R protein, humanGlucagonGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucoseInsulinPeptide FragmentsProtein PrecursorsReceptors, Glucagon

Identifiers

PMID9525985
PMCPMC508720
OpenAlexW2111242088

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.