Interaction Between St John's Wort and Metformin?

Is There a Pharmacokinetic Interaction Between St John's Wort and Metformin?

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01726764

Enrollment

Registered

2012-11-15

Start date

2013-01-31

Completion date

2014-05-31

Last updated

2014-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression, Type 2 Diabetes

Brief summary

The goal of the study is to examine the difference of the pharmacokinetics of metformin with and without a 3 weeks pretreatment of St John's Wort. Furthermore secondary objectives include changes in GLP-1, C-peptide, serum-insulin and plasma-glucose during an oral glucose tolerance test, changes in OCT1 mRNA in plasma and changes in leptin and lipid-profile following this possible interaction.

Interventions

OTHERSt John's Wort

DRUGMetformin

Study design

Allocation

Intervention model

SINGLE_GROUP

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 64 Years

Healthy volunteers

Yes

Inclusion criteria

* Men aged 18-64 years * Homozygous for common genetic variants in the genes organic cation transporter 1/2 (OCT1/OCT2) * Normal values of biomarkers accounting for: Liver and kidney function, and normal blood glucose

Exclusion criteria

* Chronic alcohol abuse * Hypersensitivity to metformin or St John's Wort * Daily intake of drugs requiring prescription

Design outcomes

Primary

Measure	Time frame	Description
Change in Area Under Curve (AUC) 0-24h of metformin	Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion	Change in 0-24h AUC of metformin after 3 weeks of treatment with St John's Wort

Secondary

Measure	Time frame	Description
Oral glucose tolerance test (OGTT)	During the first 2 hours of each metformin ingestion	Changes in: Plasma-glucose, serum-insulin, glucagon-like peptide 1 (GLP-1) and connecting-peptides (C-peptides) during the oral glucose tolerance test, measured at 0, 0.5, 1, 1.5 and 2 hours after metformin ingestion.
Pharmacokinetics of metformin	Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion, which will be used to determine the pharmacokinetic parameters mentioned below	Determination of other pharmacokinetic parameters of metformin such as clearance (CL), absorption fraction (F), distribution volume (V), the minimum concentration at steady state (Css,min), elimination half life (T 1/2) etc.
Change in messenger RiboNucleic Acid (mRNA)	Will be measured 4 times: At inclusion (t=0 on that day), at t=0 in both periods and minimum 3 weeks after finalization of the study (t=0 on that day)	Changes in mRNA encoding OCT1 will be measured at 4 different time points to give an insight to the importance of St John's Wort effect on the OCT1 production

Other

Measure	Time frame	Description
Hypericin/hyperforin	At t=0 in 2nd period	If possible measure the concentrations of some of the active components of St John's Wort, hypericin and hyperforin

Countries

Denmark

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026