Pharmacokinetics of Metformin Intolerance

Phase 4

Completed

• Conditions: Diabetes Mellitus, Type 2; Metformin Adverse Reaction
• Interventions: Drug: Metformin Hydrochloride

• Registration Number: NCT03361878
• Lead Sponsor: NHS Tayside

Brief Summary

Pharmacokinetic study of metformin intolerance

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2014-05-04
• Primary Completion: 2016-05-05
• Study Completion: 2016-05-05
• Status Verified: 2017-11
• Study First Submitted: 2017-11-29
• Study First Submitted QC: 2017-11-29
• Last Update Submitted: 2017-11-29
• Study First Posted: 2017-12-05
• Last Update Posted: 2017-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• White European
• Type 2 diabetes
• Meet criteria for tolerance or intolerance as described

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin Intolerant	Metformin Hydrochloride	-
Metformin Tolerant	Metformin Hydrochloride	-

Primary Outcome Measures

Name	Time	Method
Metformin AUC	24 hours	Area under the metformin concentration-time curve

Secondary Outcome Measures

Name	Time	Method
Lactate	24 hours	Change in lactate concentration (incremental AUC)