Changes in the metabolome after treatment with canagliflozin in patients with type 2 diabetes
Authors' conclusion
In the largest metabolomics study of SGLT2i in humans performed to date, treatment with canagliflozin was associated with significant changes in 32 metabolites, of which 21 were reported for the first time. These may have importance for understanding the beneficial effects of SGLT2i on cardiovascular, metabolic and renal outcomes that occur independently of glucose alterations.
Study context
- Population
- Canagliflozin Cardiovascular Assessment Study Programme participants with type 2 diabetes and high cardiovascular riskof the 10,142 Canagliflozin Cardiovascular Assessment Study Programme participants, 165 metabolites included in the final analysis
- Participants
- 955 participants
- Comparison
- Treatment with canagliflozin compared with placebo
- Interventionn = 629
- Controln = 326
- Outcome
- Metabolite changes
- Follow-up
- 52-week
Methodological detailsbaseline and 52-week follow-up plasma samples, high performance liquid chromatography coupled to mass spectrometry, linear models with adjustment by age, gender and body mass index
- Baseline and 52-week follow-up plasma samples
- High performance liquid chromatography coupled to mass spectrometry
- Linear models with adjustment by age, gender and body mass index
Main finding
As reported in the abstract
Upregulated metabolites
19
Downregulated metabolites
13
No change
133
Further findings
Most upregulated metabolites
- Malonate fold change
- 1.31
- 3-hydroxybutyrate fold change
- 1.33
- 2-oxobutanoate fold change
- 1.31
Most downregulated metabolites
- Glucose fold change
- 1.12
- Prephenate fold change
- 1.38
- Glyceraldehyde fold change
- 1.12
Pathway analysis
- Upregulation of the lipid pathways and downregulation of amino acid pathway
- 3-indol-propionic acid in the antioxidant system altered
Original publication
Changes in the metabolome after treatment with canagliflozin in patients with type 2 diabetes. Heart. Published 5 June 2026. doi:10.
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