SGLT2 inhibitors and thiazide enhance excretion of DEHP toxic metabolites in subjects with type 2 diabetes: A randomized clinical trial

• Published in: Environmental research Vol. 192; p. 110316
• Main Authors: Mengozzi, Alessandro, Carli, Fabrizia, Guiducci, Letizia, Parolini, Federico, Biancalana, Edoardo, Gastaldelli, Amalia, Solini, Anna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2021
• Subjects: Diabetes Mellitus, Type 2 - drug therapy; Diethylhexyl Phthalate; Environmental Exposure; Environmental pollutants; excretion; Exposure assessment; feces; Humans; hydrochlorothiazide; hypertension; metabolism; metabolites; noninsulin-dependent diabetes mellitus; Phthalate; phthalates; Phthalic Acids; potassium; randomized clinical trials; risk; SGLT2 inhibitors; sodium; Sodium-Glucose Transporter 2 Inhibitors; therapeutics; Thiazides; toxicity; urine; Phthalate; Environmental pollutants; Thiazides; Exposure assessment; SGLT2 inhibitors
• ISSN: 0013-9351; 1096-0953; 1096-0953
• DOI: 10.1016/j.envres.2020.110316

Phthalates are non-persistent pollutants related to impaired metabolism and high cardiovascular risk. Their toxic metabolites are eliminated through urine and feces. Prevention policies are considered by the governments, although no therapeutic strategy to facilitate their elimination from the human body has been proposed so far. Aim of the present study was to verify, for the first time in humans, whether diuretics might be able to enhance phthalates’ toxic metabolites urinary output. We conducted a two-armed, parallel-design, randomized clinical trial. Thirty patients with type 2 diabetes and hypertension received a four week-treatment with Dapagliflozin 10 mg or Hydrochlorothiazide 12.5 mg. 24-hours urine were collected to measure urinary excretion of three major 2-ethylhexyl-phthalate (DEHP) metabolites, i.e. mono 2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono 2-ethyl-5-hydroxyhexyl phthalate (MEHHP). 24-h urinary excretion of DEHP and MEHP was increased (+44%, p = 0.036; +49%, p = 0.0016) while MEOHP e MEHHP showed only a positive trend (+25%, p = 0.016; +36%, p = 0.062). Irrespective of the specific treatment, induced variations of daily urinary eliminations of MEHP metabolites were related with the 24-h urinary sodium (r = 0.42, p = 0.0226) and potassium (r = 0.54, p = 0.0026) excretion. Also, DEHP and MEOHP were related to sodium (r = 0·43, p = 0.0205; r = 0·44, p = 0.0168 respectively) but not to potassium. Urinary phthalates excretion seems to occur mainly through sodium- and potassium-related mechanisms, apparently independent from the different diuretic effect. Both thiazide diuretics and SLGT2 inhibitors are effective into the removal of phthalates metabolites from the human body, reducing the human tissues’ exposure to their toxicity. •SGLT2i or thiazide increases urinary excretion of phthalates metabolites.•The effect is independent from the diuretic class.•The increase of urinary MEHP excretion is positively related to sodium one.•Through diuretics, it is possible to enhance phthalates elimination from the body.•Urine samples might lead to overestimate exposure if subjects are on diuretics.