Metformin has no impact on nitric oxide production in patients with pre-diabetes

Abstract

Aims/introduction: The authors evaluated the impact of different dose of metformin on NO (nitric oxide) production in subjects with pre-diabetes.

Materials and methods: The metformin-naïve patients from one Diabetic Center with newly diagnosed pre-diabetes, without cardio-vascular diseases, were randomized (based on the identification number, individual for each inhabitant in the country) for treatment with different doses of metformin (group A 3 × 500 mg, group B 3 × 1000 mg) for 12 weeks. Then, the subjects from group B were switched to dose 3 × 500 for the last 3 weeks. The wide panel of L-arginine/NO pathway metabolites concentrations was assessed using the liquid chromatography-mass spectrometry technique.

Results: Between October 2017 and December 2018, 36 individuals were initially randomized to intervention groups. The study was completed with 25 subjects: 14 patients in group A, 11 in group B; also 11 healthy volunteers were recruited. There was no difference between participants with pre-diabetes and healthy volunteers as regards the baseline characteristics except for fasting glucose and fatty liver. The decrease of L-citrulline concentration only was reported for treatment groups during the intervention period, with no change for the other NO-production related substances.

Conclusion: It was the first study on the in vivo release of NO in humans with different metformin doses in patients with pre-diabetes. Metformin did not seem to increase NO production measured by the citrulline plasma levels, irrespective of the dose. The citrulline concentration change might indicate the drug impact on the condition of the enterocytes.

Keywords: Metformin; NO-nitric oxide; Pre-diabetic state.