title: Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes.
abstract: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to have BP-lowering effect in addition to blood glucose-lowering effect, however, its mechanism is still unknown. This study aimed to investigate the mechanism of blood pressure (BP) lowering effects of SGLT2 inhibitors using 24-h urinary collection in obese type 2 diabetes patients.
  
  
  
  Twenty patients with type 2 diabetes (age 48.2 ± 10.7 years, BMI 33.0 ± 4.9 kg/m2) were enrolled. Urine volume, 24-h urinary glucose and sodium excretion, and BP at baseline and 2 weeks and 6 months after administration were measured. Body weight, glycosylated hemoglobin, and BP were evaluated before and 1, 3, and 6 months after SGLT2 inhibitor administration. We evaluated the changes in urine volume and urinary excretion of glucose and sodium as well as correlations among urine volume and urinary sodium glucose excretion at 2 weeks and 6 months after administration of the SGLT2 inhibitors. Furthermore, we investigated the correlations between changes in BP and urinary excretion of sodium and glucose at the same time.
  
  
  
  Two weeks after administration, systolic BP (SBP) significantly decreased (128.5 ± 11.0 to 123.2 ± 9.8 mmHg, P = 0.0314), but diastolic BP (DBP) did not (74.4 ± 10.4 to 73.4 ± 8.5 mmHg, P = 0.5821). The decreased SBP significantly correlated with increased urinary glucose excretion (R = -0.62, P = 0.0073), but not increased urinary sodium excretion. At 6 months, SBP (118.6 ± 11.0 mmHg, P = 0.0041) and DBP (68.4 mmHg, P = 0.0363) significantly decreased. The decreased SBP significantly correlated with increased urinary sodium excretion (R = -0.60, P = 0.0014), but not increased urinary glucose excretion.
  
  
  
  SGLT2 inhibitors significantly decreased SBP after 1 month and DBP after 6 months in obese patients with type 2 diabetes. The main mechanism of the BP-lowering effect may be plasma volume reduction by osmotic diuresis at 2 weeks and by natriuresis at 6 months after SGLT2 inhibitor administration.
authors.affiliation: Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kawasoe
authors.affiliation: Uenomachi-Kajiya Clinic, Kagoshima, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Maruguchi
authors.affiliation: Uenomachi-Kajiya Clinic, Kagoshima, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kajiya
authors.affiliation: Uenomachi-Kajiya Clinic, Kagoshima, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Uenomachi
authors.affiliation: Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan. miyatam@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyata
authors.affiliation: Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawasoe
authors.affiliation: Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Kubozono
authors.affiliation: Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohishi
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000652:urine; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology / Q000652:urine; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology / Q000652:urine; D010953:Plasma Volume / Q000187:drug effects / Q000502:physiology; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D001559:Benzhydryl Compounds; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C529054:dapagliflozin; C572941:ipragliflozin; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
keywords: Blood pressure; Natriuresis; Osmotic diuresis; SGLT2 inhibitor; Type 2 diabetes