A randomised clinical trial testing the safety of and metabolic responses to short-term duodenal infusion of recombinant RORDEP1 in healthy men – published online 23/05/2026

Joachim Gæde, Yong Fan, Liwei Lyu, Lærke Smidt Gasbjerg, Peter Rossing, Bolette Hartmann, Jens Juul Holst, Asger B. Lund, Filip K. Knop, Oluf Pedersen

RUMTOR-derived peptide 1 (RORDEP1), an irisin-like polypeptide synthesised by Ruminococcus torques strains in the healthy human gut microbiome, increases hepatic insulin sensitivity and adipose thermogenesis, and regulates incretin release in rodents. In this issue, Gæde et al (https://doi.org/10.1007/s00125-026-06751-0) present findings from a first-in-human randomised clinical trial exploring the safety and tolerability of, and metabolic responses to, a duodenal infusion of recombinant RORDEP1 in young healthy men. They report that, compared with placebo, the intraduodenally infused recombinant RORDEP1 increased plasma glucagon-like peptide-1 and insulin, while plasma gastric inhibitory peptide and glucose were decreased. In parallel, RORDEP1 induced an increase in whole body insulin sensitivity. The authors conclude that these findings warrant future longer-term clinical trials examining daily administration of RORDEP1 in slow-release entero-coated capsules.

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