Low metformin dose and its therapeutic serum concentration in prediabetes

Abstract

This prospective study aimed to analyze whether the patients with pre-diabetes (pre-DM) reach the TC (therapeutic concentration) of the metformin during repeated, low, constant drug dose. The guidelines do not recommend any metformin dose for this group of patients. Based on the previous study after a dose of 1700 mg/day the patients seem to reach the therapeutic drug concentration, which guarantees the glycemic effect. Twenty patients with new-diagnosed pre-DM were treated with a 1500 mg/day regimen of the metformin for 15 weeks. The serum concentration of the drug was assessed by liquid chromatography-mass spectrometry technique at 6 and 15 week of the treatment. The correlation of the serum metformin concentration with BMI (body mass index) and patients’ weight was also performed. The mean metformin concentration was: 4.65 μmol/L (± 2.41) and 5.41 μmol/L (± 3.44) (p = 0.27) after 6 and 15 weeks of the treatment respectively. There was a positive correlation between the serum concentration of the metformin and body weight (but not BMI) in the 15th week of the therapy (p = 0.04)- the higher body weight the higher concentration of the metformin. Patients with pre-diabetes can be successfully treated with a low dose of metformin, to reach the drug’s therapeutic concentration. Body weight can impact the metformin serum concentration during long-term treatment what should be taken into consideration when choosing the dose because of its pleiotropic effect e.g. on the cardiovascular system via reduction of the oxidative stress and would be not connected with the drug’s hypoglycemic effect.ClinicalTrials.gov number: NCT03398356; date of first registration: 01/07/2018.

Let-7 underlies metformin-induced inhibition of hepatic glucose production

“…The therapeutic concentrations of metformin in human plasma ranged from 0.1 to 20.7 (median 4.5) μM ( 20 – 23 ). After patients with prediabetes were treated with metformin at 1,500 mg/day for 15 wk, a mean plasma metformin concentration of 5.41 μM was obtained ( 24 ). Using a physiologically based pharmacokinetic model of mice, the simulated mean metformin concentrations were reported to be 3.5 μM, 6.5 μM, and 9.2 μM in the plasma and 29.2 μM, 53.6 μM, and 76.8 μM in the liver, following a therapeutic daily dosing regimen of 1,000 mg, 2,000 mg, and 3,000 mg in humans, respectively ( 19 ).…”

Metformin does not slow cyst growth in the PCK rat model of polycystic kidney disease

“…The therapeutic concentration for MET is not well defined but has been described to range from 0.1 to 20.7 μmol/L (Sutkowska et al, 2021), 6–30 μmol/L in type 2 diabetic patients (Chang et al, 2022), or 10–40 μmol/L in rodents (He & Wondisford, 2015). Serum levels of ~5–10 μmol/L are similar to that seen in patients treated with the usual clinical dose (i.e., 1.5–2.5 g/day; Leonhard et al, 2019).…”

Factors contributing to variability in metformin concentration in polycystic ovary syndrome

“…Expanding beyond diabetes, another study in lung cancer patients showed significant individual variation in metformin concentrations across tissues, emphasizing the importance of exploring metformin's distribution in different indications ( 18 ). Additionally, research in prediabetic individuals found that a lower dose could achieve therapeutic serum concentrations, with a noted correlation between serum levels and body weight, opening new avenues for metformin's use and dosage considerations in non-diabetic conditions ( 19 ). These findings underscore the complexity of metformin's pharmacokinetics and the need for tailored therapeutic strategies across different patient populations.…”