Diabetes Mellitus, Type 1 Clinical Trial
Official title:
The Effects of Empagliflozin on Functional and Structural Arterial Wall Characteristics
Introduction: Diabetes mellitus is characterized by impaired arterial function and high
incidence of cardiovascular events. Metformin and most recent antidiabetic groups of drugs,
SGLT2 inhibitors, were in previous studies shown to reduce cardiovascular events. Until now,
direct effect of empagliflozin on arterial function and its comparison to metformin was not
studied yet.
Aim: The aim of the present study is to explore and compare potential direct effects of
empagliflozin and metformin on arterial functional and structural arterial wall
characteristics in patients with type 1 diabetes mellitus.
Methods: Patients with type 1 diabetes mellitus are randomized into four groups: 1)
empagliflozin (25 mg daily), 2) metformin (2000 mg daily), 3) combination (empagliflozin 25
mg daily and metformin 2000 mg daily) and 4) control (placebo). At inclusion and after 12
weeks treatment, arterial function is assessed: endothelial function (brachial artery
flow-mediated dilation (FMD), reactive hyperemia index (RHI)) and arterial stiffness (carotid
pulse wave velocity (PWV), carotid-femoral PWV (cfPWV) and common carotid artery stiffness
(β-stiffness)).
Introduction: Diabetes mellitus is characterized by impaired arterial function and high
incidence of cardiovascular events. Metformin and most recent antidiabetic groups of drugs,
SGLT2 inhibitors, were in previous studies shown to reduce cardiovascular events. Until now,
direct effect of empagliflozin on arterial function and its comparison to metformin was not
studied yet.
Aim: The aim of the present study is to explore and compare potential direct effects of
empagliflozin and metformin on arterial functional and structural arterial wall
characteristics in patients with type 1 diabetes mellitus.
Methods: Patients with type 1 diabetes mellitus are randomized into four groups: 1)
empagliflozin (25 mg daily), 2) metformin (2000 mg daily), 3) combination (empagliflozin 25
mg daily and metformin 2000 mg daily) and 4) control (placebo). At inclusion and after 12
weeks treatment, arterial function is assessed: endothelial function (brachial artery
flow-mediated dilation (FMD), reactive hyperemia index (RHI)) and arterial stiffness (carotid
pulse wave velocity (PWV), carotid-femoral PWV (cfPWV) and common carotid artery stiffness
(β-stiffness)).
Background:
Diabetes mellitus is characterized by chronic hyperglycaemia causing chronic microvascular
and macrovascular complications. Among the microvascular complications, diabetic retinopathy,
neuropathy and nephropathy are included. Macrovascular complications include atherosclerotic
brain-vascular disease, coronary disease and peripheral arterial disease. Chronic
complications of diabetes pose a greater risk of disability, development of blindness, renal
failure, neuropathy and cardiovascular disease. Consequently, a good glycemic control is
crucial to protect the patients from the development of chronic complications. In this
regard, glycemic control is of primary importance, as well as the choice of treatment that
can further improve the functioning of the arteries and thus protect against the onset of
cardiovascular damage or complications.
For the treatment of hyperglycemia patients with type 1 diabetes need insulin. Some oral
anti-diabetics have been found to improve glycemic control, reduce insulin consumption (the
total daily insulin dose), and also protect against the development of cardiovascular
complications. Such effects have been shown in clinical studies for metformin. The latter
improved from endothelium-dependent relaxation of the arteries and reduced insulin
resistance, but most studies were performed in patients with type 2 diabetes and studies in
type 1 diabetes are limited.
A novel group of oral antidiabetics are SGLT2 inhibitors, such as empagliflozin, reduce
glucose reabsorption in proximal kidney tubules and increase glucose excretion through urine.
Most of the previous studies on the efficacy of empagliflozin basic antidiabetic activity and
additional effects have been performed in patients with type 2 diabetes. They were shown to
improve glyceamia control and also reduced blood pressure body weight. In patients with type
1 diabetes, favorable effects of empagliflozin on the reduction of arterial wall stiffness
and blood pressure reduction were observed, but no systematic studies were performed yet and
the mechanisms behind the beneficial effects are not known yet.
Methods:
Type 1 diabetes mellitus patients are being recruited. The patients are equally randomized
into 4 groups that receive one of the three drugs in addition to insulin. The groups were as
follows: 1) empagliflozin group (receiving 25 mg daily), 2) metformin group (receiving 2000
mg daily), combination group (receiving empagliflozin 25 mg daily and metformin 2000 mg
daily) and 4) control group (receiving placebo). The duration of the study period is 12
weeks. All subjects are voluntarily participating in this study. The study was approved by
the National Medical Ethics Committee of Slovenia.
At the beginning of the study, a complete history and full medical examination of each
patient are performed. At inclusion to the study and after 12 weeks of treatment, arterial
function measurements are performed, comprising of i) measurements of endothelial function
(brachial artery flow-mediated dilation (FMD), reactive hyperemia index (RHI)); and ii)
measurements of arterial stiffness (carotid artery pulse wave velocity (PWV), carotid-femoral
PWV (cfPWV) and common carotid artery stiffness (β-stiffness)). Additionally, venous blood
samples are obtained at the beginning and at the end of the study period. Automated
sphygmomanometer is used for blood pressure measurements. Ultrasound measurements are
obtained on Aloka ProSound alpha7 machine with integrated high resolution eTracking system.
Endothelial function, by means of brachial artery FMD, was assessed in accordance to the
current guidelines. Reactive hyperemia index is measured using Endopat 2000 device (Itamar
Medical Ltd., Caesarea, Israel), while cfPWV is obtained using SphygmoCor device (AtCor
Medical, Sydney, Australia) with SphygmoCor CvMS software (version 9).
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04030091 -
Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus
|
Phase 4 | |
Terminated |
NCT03605329 -
Evaluation of the Severity of Cardiovascular Autonomic Neuropathy in Type 1 Diabetic Patients With OSAS
|
N/A | |
Completed |
NCT01696266 -
An International Survey on Hypoglycaemia Among Insulin-treated Patients With Diabetes
|
||
Recruiting |
NCT06050642 -
Study of the Impact of PROximity Support for Patients With Type 1 DIABetes Treated With an Insulin Pump or Closed Loop.
|
N/A | |
Completed |
NCT05107544 -
Metabolic, Physical Fitness and Mental Health Effects of High Intensity Interval Training (HIIT) in Adolescents With Type 1 Diabetes
|
N/A | |
Active, not recruiting |
NCT04443153 -
Adapting Diabetes Treatment Expert Systems to Patient in Type 1 Diabetes
|
N/A | |
Completed |
NCT04521634 -
Glycaemic Variability in Acute Stroke
|
||
Completed |
NCT04569994 -
A Study to Look at the Safety of NNC0363-0845 in Healthy People and People With Type 1 Diabetes
|
Phase 1 | |
Completed |
NCT04089462 -
Effects of Frequency and Duration of Exercise in People With Type 1 Diabetes A Randomized Crossover Study
|
N/A | |
Completed |
NCT03143816 -
Study Comparing Prandial Insulin Aspart vs. Technosphere Insulin in Patients With Type 1 Diabetes on Multiple Daily Injections: Investigator-Initiated A Real-life Pilot Study-STAT Study
|
Phase 4 | |
Completed |
NCT01892319 -
An International Non-interventional Cohort Study to Evaluate the Safety of Treatment With Insulin Detemir in Pregnant Women With Diabetes Mellitus. Diabetes Pregnancy Registry
|
||
Recruiting |
NCT04039763 -
RT-CGM in Young Adults at Risk of DKA
|
N/A | |
Completed |
NCT04042207 -
Diabeloop for Highly Unstable Type 1 Diabetes
|
N/A | |
Not yet recruiting |
NCT06068205 -
COMPARATIVE ANALYSIS OF THE MORPHO-MECHANICAL PROPERTIES OF RED BLOOD CELLS EXTRACTED FROM DIABETIC PATIENTS WITH AND WITHOUT MICROVASCULAR COMPLICATIONS
|
||
Recruiting |
NCT05909800 -
Prolonged Remission Induced by Phenofibrate in Children Newly Diagnosed With Type 1 Diabetes.
|
Phase 2 | |
Active, not recruiting |
NCT04974528 -
Afrezza® INHALE-1 Study in Pediatrics
|
Phase 3 | |
Completed |
NCT04530292 -
Home Intervention and Social Precariousness in Childhood Diabetes
|
N/A | |
Completed |
NCT05428943 -
OPT101 in Type 1 Diabetes Patients
|
Phase 1 | |
Recruiting |
NCT03988764 -
Monogenic Diabetes Misdiagnosed as Type 1
|
||
Completed |
NCT05597605 -
The SHINE Study: Safety of Implant and Preliminary Performance of the SHINE SYSTEM in Diabetic Subjects
|
N/A |