Metformin's Effect on Drug Metabolism in Patients With Type 2 Diabetes
Status:
Recruiting
Trial end date:
2022-03-01
Target enrollment:
Participant gender:
Summary
Type 2 diabetes is a major public health concern. It is widely established that type 2
diabetes in linked to activated innate immunity and increased levels of C-reactive protein
and interleukin-6 (IL-6) in plasma. Studies in humans and in liver cells has shown that IL-6
downregulates important drug metabolizing enzymes in the liver (cytochrome P450 (CYP)
enzymes). More than half of the most prescribed drugs are eliminated by biotransformation of
these enzymes.
The investigators have previously shown that initiating glucose-lowering treatment (e.g.
metformin, sulphonylureas and insulin) leads to decreased therapeutic efficacy of the
blood-thinning vitamin-K antagonist warfarin. Due to the non-specific effect of glucose
lowering drugs, the investigators hypothesize that this is caused by the glucose-lowering
effect rather than drug-drug interactions caused by the individual drugs.
Based on the proposal that reversal of increased plasma glucose affects drug metabolism, the
investigators will perform a clinical pharmacokinetic trial. The purpose of the study is to
elucidate whether initiation of glucose-lowering treatment causes altered drug metabolism
among patients with type 2 diabetes. The study will include newly diagnosed and untreated
type 2 diabetes patients who will ingest a 6-drug cocktail consisting of probes for specific
CYP enzymes. Plasma and urine will be drawn over 6 hours to determine concentrations of the
drugs and their metabolites. Patients will then initiate metformin treatment and to assess
both short- and long-term impact of glucose-lowering, the same 6-drug cocktail will be
ingested, and concentrations measured, after three weeks and three months. To help understand
the mechanism and the putative involvement of inflammation, markers of inflammation such as
cytokines, transcription factors, etc. will also be assesses.