Effect of dapagliflozin on the serum metabolome in patients with type 2 diabetes mellitus

Abstract

Objectives: SGLT-2 inhibitors have been shown to exert cardio- and renoprotective actions. We aimed to investigate the underlying mechanisms using ¹H-NMR based metabolomics in patients with type-2 diabetes mellitus who received dapagliflozin.

Methods: 50 patients with type 2 diabetes mellitus, inadequately controlled on metformin monotherapy (HbA1c > 7%) received dapagliflozin for 3 months and 30 matched patients received insulin degludec for 3 months. Clinical and laboratory values, as well as ¹H-NMR based metabolomics were assessed before treatment and after completion of 3 months of treatment.

Results: Dapagliflozin reduced weight, body mass index, systolic and diastolic blood pressure significantly. Using ¹H-NMR based metabolomics, the dapagliflozin group showed a good separation with a degree of overlap before and after treatment initiation. Regarding targeted metabolomics, dapagliflozin increased serum ketone, citrate and tryptophan levels compared with insulin. On the other hand, serum taurine, threonine and mannose levels were significantly decreased following dapagliflozin administration.

Conclusions: Dapagliflozin led to a small, but significant change in serum metabolome. The observed changes may indicate improvement in energy metabolism, reduction in inflammatory activity and decreased insulin resistance which may provide further evidence of the agent's observed cardiac and renal protection. The study was registered with ClinicalTrials.gov (identifier: NCT02798757).

Supplementary information: The online version contains supplementary material available at 10.1007/s40200-024-01508-1.

Keywords: Dapagliflozin; Insulin; Metabolomics; SGLT-2.