We aimed to identify metabolites to predict patients' response to
glucose lowering treatment during the first 5 years after detection of
type 2 diabetes. Metabolites were measured by GC-MS in baseline samples from 346 screen-detected
type 2 diabetes patients in the ADDITION-NL study. The response to treatment with
metformin and/or sulphonylurea (SU) was analysed to identify metabolites predictive of 5 year HbA1c change by multiple regression analysis. Baseline
glucose and 1,5 anhydro-
glucitol were associated with HbA1c decrease in all medication groups. In patients on SU no other metabolite was associated with HbA1c decrease. A larger set of metabolites was associated with HbA1c change in the
metformin and the combination
therapy (metformin + SU) groups. These metabolites included metabolites related to liver metabolism, such as
2-hydroxybutanoic acid, 3-hydroxybutanoic
acid, 2-hydroxypiperidine and 4-oxoproline). Metabolites involved in oxidative stress and
insulin resistance were higher when the HbA1c decrease was larger in the
metformin/sulphonylurea group. The associations between baseline metabolites and responsiveness to medication are in line with its mode of action. If these results could be replicated in other populations, the most promising predictive candidates might be tested to assess whether they could enhance personalised treatment.