The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus.
BACKGROUND
Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension, contributing to cardiovascular complications. Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness, and is an important contributing factor for hypertension. Since the sodium glucose cotransport-2 (SGLT2) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus, we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity.


METHODS
Blood pressure, arterial stiffness, heart rate variability (HRV) and circulating adrenergic mediators were measured during clamped euglycaemia (blood glucose 4-6 mmol/L) and hyperglycaemia (blood glucose 9-11 mmol/L) in 40 normotensive type 1 diabetes mellitus patients. Studies were repeated after 8 weeks of empagliflozin (25 mg once daily).


RESULTS
In response to empagliflozin during clamped euglycaemia, systolic blood pressure (111 ± 9 to 109 ± 9 mmHg, p = 0.02) and augmentation indices at the radial (-52% ± 16 to -57% ± 17, p = 0.0001), carotid (+1.3 ± 1 7.0 to -5.7 ± 17.0%, p < 0.0001) and aortic positions (+0.1 ± 13.4 to -6.2 ± 14.3%, p < 0.0001) declined. Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition. Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions (p ≤ 0.0001), while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia (5.7 ± 1.1 to 5.2 ± 0.9 m/s, p = 0.0017). HRV, plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions.


CONCLUSIONS
Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects. The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition, including glucose lowering, antihypertensive and weight reduction effects.


BACKGROUND



BACKGROUND
NCT01392560.
Division of Nephrology, University Health Network, University of Toronto, Toronto General Hospital, 585 University Ave, Toronto 8N-845, M5G 2N2, Ontario, Canada. david.cherney@uhn.on.ca.
David Zi
DZ
Cherney
Bruce A
BA
Perkins
Nima
N
Soleymanlou
Ronnie
R
Har
Nora
N
Fagan
Odd Erik
OE
Johansen
Hans-Juergen
HJ
Woerle
Maximilian
M
von Eynatten
Uli C
UC
Broedl
D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
D001559:Benzhydryl Compounds; D005960:Glucosides; C570240:empagliflozin