Longitudinal Taxonomic and Predicted Functional Gut Microbiome Responses to Tirzepatide and Semaglutide: An Exploratory Secondary Analysis of the OMDOT ‐1 Randomized Controlled Trial
Authors' conclusion
Tirzepatide and semaglutide were associated with partially distinct taxonomic changes, accompanied by broadly similar predicted functional patterns. These longitudinal findings complement, while remaining distinct from, Week-16 shotgun metagenomic endpoint analyses.
Study context
- Population
- Participants with Type 2 diabetes from a randomized controlled trial comparing tirzepatide, semaglutide and conventional treatmentparticipants included in this secondary analysis
- Participants
- 36 participants
- Comparison
- Tirzepatide and semaglutide vs conventional treatment
Methodological detailslongitudinal mixed-effects models, 16S rRNA gene sequencing, adjusted for baseline body mass index
- Longitudinal mixed-effects models
- 16S rRNA gene sequencing
- Adjusted for baseline body mass index
Primary result
As reported in the abstract
Beta diversity
- No significant between-group differences in beta diversity
Further findings
Alpha diversity
- Alpha diversity increased predominantly in the tirzepatide group, with a significant time-by-treatment interaction versus control
Longitudinal genus trajectories relative to control
- Differed for Romboutsia_B, Barnesiella and Ruminococcus_E with both treatments and Vescimonas with tirzepatide
- q < 0.05
Correlation of longitudinal effects on predicted EC features between tirzepatide and semaglutide
- Predicted EC features
- 2106
- Concordant direction
- 67.1%
- Pearson r
- 0.450
- p
- P < 0.001
Predicted functional changes, treatment versus control
- Predicted functional changes involving energy and carbohydrate metabolism
Original publication
Longitudinal Taxonomic and Predicted Functional Gut Microbiome Responses to Tirzepatide and Semaglutide: An Exploratory Secondary Analysis of the OMDOT ‐1 Randomized Controlled Trial. Diabetes Obes Metab. Published 8 November 2026. doi:10.
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