Background: Favourable cardiovascular effects of SGLT2 inhibitors have been clearly revealed, whereas the underlying mechanism(s) still remain unknown. We explored the anti-oxidative action of empagliflozin (alone and in combination with metformin) in type 1 diabetes mellitus (T1DM) patients.

Methods: Forty T1DM male patients (age 44.7 ± 2.5 years, BMI 28.3 ± 0.6 kg/m2) were equally randomised into four groups: 1) control (placebo), 2) empagliflozin (25 mg daily), 3) metformin (2000 mg daily) and 4) combination (empagliflozin 25 mg daily and metformin 2000 mg daily). Oxidative stress parameters were assessed at inclusion and after 12 weeks of treatment, comprising of total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), isoprostane, interleukin 6 (IL6) and advanced oxidation protein products (AOPP). One-way analysis of variance (ANOVA) with Bonferroni post-test was used for statistical analysis.

Results: Empagliflozin in combination with metformin significantly improved antioxidative status parameters by increasing TAS for up to 1.07-fold (P<0.01), SOD for up to 1.08-fold (P<0.001) and GPx for up to 1.15-fold (P<0.01), whereas empagliflozin or metformin alone were less effective. The prooxidants significantly decreased in groups treated with empagliflozin alone or empagliflozin in combination with metformin: isoprostane for up to 1.26-fold (P<0.001) and IL6 for up to 1.34-fold (P<0.01); whereas the level of AOPP significantly decreased only in the group treated with empagliflozin and metformin combination (for up to 1.22-fold; P<0.01). The levels of oxidative stress parameters in the control group remained unchanged.

Conclusion: We found that empagliflozin in combination with metformin provided powerful antioxidative defense in T1DM patients. The results could at least partially explain the beneficial effects of the two drugs beyond glucose control. Antioxidant activity should be focused on in further large clinical studies.


M. Janic: None. M. Lunder: None. M. Sabovic: None. A. Janez: None.

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