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Article History

Received: 16 March 2025

Accepted: 16 May 2025

First Online: 18 September 2025

Acknowledgements

: The authors would like to thank all study participants and acknowledge the laboratory assistance from S. M. Schmidt, I. al Nachar, A. von der Lieth and research coordinator M. G. Pedersen, Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark. Some of the data in this article were presented as an abstract at the ADA’s 79th Scientific Sessions in San Francisco 2019.

: The datasets generated during and/or analysed during the current study are available from the corresponding author on request.

: Open access funding provided by Copenhagen University. This study was supported by grants from the Aase and Ejnar Danielsen’s Foundation and the Novo Nordisk Foundation. LY2409021 was offered free of charge by Eli Lilly and Company.

: ABL has served on scientific advisory panels and/or received honoraria or research support from Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Zealand Pharma. JJH has served on advisory boards for Novo Nordisk. JJH and MMR are minority shareholders and cofounders of Antag Therapeutics. NJWA has received research support, personal fees and speaker fees from EvoSep, Mercodia, Novo Nordisk, Merck/MSD, Roche and Boehringer Ingelheim. TV has served on scientific advisory panels, been part of speaker’s bureaus, served as a consultant to and/or received research support from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Novo Nordisk, Carmot/Roche, Regor, Sanofi, Sun Pharmaceuticals and Zealand Pharma. FKK is currently employed by Novo Nordisk, the present work was done independently of Novo Nordisk. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.

: CT-BJ was involved in planning of the study and conducted the clinical experiments and was responsible for the statistical analyses and drafting the manuscript. ABL was involved in conceptualisation of the study and statistical analyses and was involved in writing of the manuscript. SH was involved in planning of the study and writing of the manuscript. MMA conducted clinical experiments. CPH and JHS recruited participants. MMR and CJK were involved in analysis and interpretation of data. FD processed and analysed NEFA data. GvH processed and analysed glucose and glycerol tracer data. NJWA processed and analysed amino acid data. JJH and BH processed and analysed glucagon, GLP-1 and GIP data. TV and JJH were involved in planning of the study. FKK conceptualised the study and was involved in planning of the study, interpretation of data and writing of the manuscript. All authors critically reviewed, edited and approved the manuscript. CT-BJ and FKK are the guarantors of this work and, as such, had full access to all the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis.