Trial reportDiabetologia2025
Using glucagon receptor antagonism to evaluate the physiological effects of extrapancreatic glucagon in totally pancreatectomised individuals: a randomised controlled trial.
Trial report in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02944110 (Delineation of the Diabetogenic Role of Extrapancreatic Glucagon in Totally Pancreatectomised Patients Using Glucagon Receptor Antagonism), which is not on this map. Not yet cited in PubMed.
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Delineation of the Diabetogenic Role of Extrapancreatic Glucagon in Totally Pancreatectomised Patients Using Glucagon Receptor Antagonism
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0 citing papers in PubMed.
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPrevious studies have indicated that 29-amino-acid glucagon (i.e. 'pancreatic' glucagon) circulates in totally pancreatectomised individuals and that a postprandial glucagon response can be detected. Using a glucagon receptor antagonist (GRA), we investigated the possible role of extrapancreatic glucagon on glucose, lipid and amino acid metabolism in totally pancreatectomised individuals.
methodIn a randomised, crossover study, nine totally pancreatectomised individuals and nine matched healthy control individuals were given, in randomised order (planned on the website www.random.org ), 300 mg GRA (LY2409021; Eli Lilly) or placebo 10 h before two 3 h OGTTs. The experiment was double-masked (i.e. both participants and investigator were masked for the type of the experimental day [day A vs day B]). The key inclusion criteria for the healthy control participants were age >18 years, normal fasting plasma glucose and HbA
resultsGlucagon concentrations remained unchanged from fasting concentrations during the OGTT in the totally pancreatectomised individuals on both study days and circulating glucose, lipids and amino acid levels were unaffected by treatment with LY2409021 compared with placebo. In the control group, LY2409021 resulted in relevant pharmacodynamic effects, including lower fasting plasma glucose (4.7 [0.1] vs 5.2 [0.1] mmol/l, p=0.001) and augmented concentrations of amino acids in plasma, compared with placebo. CONCLUSIONS/
interpretationWe conclude that inhibition of the glucagon receptor using LY2409021 during OGTT in totally pancreatectomised individuals does not produce detectable effects on glucose, lipid or amino acid metabolism, ruling out metabolic effects of extrapancreatic glucagon.
trial registrationClinicalTrials.gov (NCT02944110).
fundingThis study was supported by grants from the Aase and Ejnar Danielsen's Foundation and the Novo Nordisk Foundation.
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