Abstract
AIM: The aims of this study were to compare the metabolic profiles of type 2 diabetes mellitus patients with metformin and insulin monotherapy, to assess the associations of metabolites with major adverse cardiovascular events (MACE) distinctly for metformin-only and insulin-only users, and to test for effect modification by the glucose-lowering treatment.
METHODS: We included 3,058 metformin-only and 558 insulin-only users from the UK Biobank. Mean concentrations of 249 metabolites of metformin and insulin users were compared with Cohen’s d, their associations with MACE were assessed with Cox regression and interaction terms were tested.
RESULTS: Mean VLDL size, HDL size, and concentrations of large and very large HDL molecules differed between insulin-only and metformin-only users. Overall, 75 metabolomic biomarkers were significantly associated with MACE in insulin-only users and 57 in metformin-only users. Significant interaction terms were observed between treatment group and albumin (protective in metformin users only) and 86 lipids/fatty acids, which were all statistically significantly associated with MACE among insulin users only.
CONCLUSION: Metformin and insulin users have different metabolic profiles and a consistent pattern emerged that the metabolic profile of metformin users is favorable compared to the one of insulin users due to a lower associated MACE risk.