Metformin Gastrointestinal Intolerance: Measurement of Mitochondrial Complex I
Status:
Completed
Trial end date:
2020-10-27
Target enrollment:
Participant gender:
Summary
Metformin is associated with a high degree of gastrointestinal intolerance, which limits the
effective use of the medication. It is proposed to be an inhibitor of liver mitochondrial
glycerophosphate dehydrogenase which results in partial blockade of mitochondrial complex 1
and inhibition of metabolism of lactate to pyruvate. There is also evidence that it is
accumulated in gastrointestinal cells, and that there are certain genotypes associated with
inclusion or lack of exclusion of the metformin from these cells. To validate this hypothesis
investigators propose to give metformin after a standard meal test to see if there is the
accumulation of lactic acid in those with gastrointestinal intolerance to metformin, compared
to those without intolerance, and to determine if these elevations of lactic acid and GI
symptoms are associated with genetic predispositions.
Aims:
1. To determine if the GI intolerance to metformin is associated with post meal elevations
of lactic acid.
a. The test will measure the inhibition of mitochondrial complex 1 levels of lactate to
pyruvate compared with non- intolerant subjects.
2. To determine if individuals with gastrointestinal symptoms and elevated lactate/pyruvate
ratios have genetic variation in the organic cation transporters.