Pharmacokinetics of Metformin Intolerance

Study Overview
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Brief Summary
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Pharmacokinetic study of metformin intolerance

Detailed Description
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This pharmacokinetic study recruited white European individuals with type 2 diabetes, who had previously been exposed to metformin and met the criteria for tolerance or intolerance. Intolerance was defined as previous exposure to metformin (maximum of 1000mg once daily for up to 8 weeks) but discontinued treatment with patient reported or documentation of gastrointestinal upset, leading to discontinuation (Criterion 1). Alternatively, intolerance was defined as inability to increase metformin dose above 500mg without experiencing gastrointestinal side-effects, despite having an HbA1c >53mmol/mol (Criterion 2). Tolerant individuals were defined as those taking 2000mg metformin daily in divided doses, with no side effects. Ten tolerant and ten intolerant individuals were recruited. Participants gave written consent. They attended the research centre fasted from midnight. A baseline blood test was taken before a single dose of oral metformin was administered at 0900, with further bloods taken at 11 time points over the following 24 hours. A 24 hour urine collection was completed. Blood samples were analysed for plasma metformin, and serum lactate concentrations.

Official Title
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Pharmacokinetics of Metformin Intolerance

Conditions
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Diabetes Mellitus, Type 2, Metformin Adverse Reaction

Intervention / Treatment
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* Drug: Metformin Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: White European Type 2 diabetes Meet criteria for tolerance or intolerance as described Exclusion Criteria: Estimated glomerular filtration rate (eGFR) <60 Cognitive impairment Pregnancy Concurrent treatment with: acarbose, cephalexin, cimetidine, pyrimethamine, or tyrosine kinase inhibitors History of gastric bypass Evidence of slowed gastric or intestinal motility

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two arms - metformin tolerant and metformin intolerant. All participants given single dose of metformin.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin Tolerant<br> | Drug: Metformin Hydrochloride<br>* Single dose of 500mg oral metformin<br>|
| Active Comparator: Metformin Intolerant<br> | Drug: Metformin Hydrochloride<br>* Single dose of 500mg oral metformin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metformin AUC | Area under the metformin concentration-time curve | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate | Change in lactate concentration (incremental AUC) | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Intolerance, Pharmacokinetics