Impact on Glycemic Variability After Treatment With Dapagliflozin on Type 2 Diabetes Patients

Type 2 Diabetes Clinical Trial

Official title:

Impact on Glycaemic Variability, Oxidative Stress and Inflammatory Disease Biomarkers After Treatment With Dapagliflozin as Dual Therapy With Metformin on Mexican Type 2 Diabetes Patients. A Randomized, Open-label Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04090580
• Other study ID #: 3089
• Status: Recruiting
• Phase: Phase 4
• Start date: August 27, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2021
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: Miguel Angel Gomez Samano, MD
• Phone: 55 54870900
• Email: gsamano83[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Glycemic variability is refered as swings in glucemic concentration throughout the day, including preprandial and postprandial glucose, and it has been proposed that could be determinant in the development in microvascular complications of type 2 diabetes (Brownlee and Hirsch 2006) SGLT2 inhibitors (SGLT2i) are a novel group of medications for treating type 2 diabetes patients but their effect on glucose variability, and oxidative stress has not been determined as a primary endpoint in clinical trials of type 2 diabetes mellitus patients. The aim of this study is to compare the effect of SGLT2 inhibition on glucose variability, oxidative stress and inflammatory disease biomarkers (VCAM-1) on new onset type 2 DM patients.

Description:

The aim of this study is to compare the effect of SGLT2 inhibition on glucose variability, oxidative stress and inflammatory disease biomarkers (VCAM-1) on new onset type 2 DM patients. Methods: The investigators will include 36 patients with type 2 diabetes diagnosis with an Hba1c ≥ 7.5% and ≤ 9%, with BMI > 25 and <45 kg/m2, drug-naïve subjects. Subjects enrolled will be randomized 1:1 to either receive a daily dosage of dapagliflozin 10 mg and 2000 mg metformin for 12 weeks (n=18) or 2000 mg metformin (n=18). Patients who do not tolerate metformin at 2000mg dose will be downtitrated to 1500 mg daily. In case patients do not tolerate 1500 mg daily, they will be excluded. Patients who do not achieve glycaemic control, another antihyperglycaemic drug can be used.

Both groups will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA), or other available in Mexico. Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit).

The main variables of interest are going to be in order of importance the delta of change (before and after study entry) of: 1.- glycaemic variability, 2.- change in Hba1c. 3.- change in oxidative stress status, 4. change in VCAM-1, 5.- change in weight, 6.- Blood pressure and 7.- waist circumference; before and after SGLT2i. The expected results are: compared to standard treatment, dapagliflozin arm will have lower glycaemic variability, higher reduction in Hba1c, lower oxidative stress, lower inflammsatory biomarker levels, and lower blood pressure

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 77 Years

Eligibility

Inclusion Criteria:

• Subjects > 18-77 years-old

• Both Male and female

• Hba1c = 7.5 % and =9%

• BMI > 25 and <45 kg/m2

• Type 2 diabetes diagnosis, drug-naïve

Exclusion Criteria:

• Hba1c > 9%

• Creatinine clearance CKD-EPI: < 60 mL/min

• LADA or Type 1 diabetes

• Gestational diabetes

• Clinically significant disease like: hepatic, hematological, oncological, psychiatric or rheumatic disease.

• Symptoms of marked uncontrolled diabetes: (marked poliuria or polidipsia + 10% weight loss prior the last 3 months enrollement)

• Known hypersensitivity to dapagliflozin or any of the excipients of the product

• eGFR persistently <45 mL/min/1.73 m2

• Unstable or rapidly progressing renal disease

• Patients with severe hepatic impairment (Child-Pugh class C)

• Any major CV event/Vascular Disease within 3 months prior to signing the consent at enrolment, as assessed by the investigator

• For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Diagnostic Test:
• Continuous glucose monitoring
Subjects enrolled will be randomized 1:1 to either receive a daily dosage of dapagliflozin 10 mg and 2000 mg metformin for 12 weeks (n=18) or 2000 mg metformin (n=18). Patients who do not tolerate metformin at 2000mg dose will be downtitrated to 1500 mg daily. In case patients do not tolerate 1500 mg daily, they will be excluded. Both groups will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA). Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit).

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán ''INCMNSZ''	Ciudad de mexico

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	AztraZeneca

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of dapagliflozin in glycemic variability	Patients from both groups (dapagliflozin + metformin and metformin) will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA). Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit) comparing glycemic variability between them. Mean difference of glycaemic variability (MAGE) calculated in mmol/L.	12 weeks
Secondary	Impact of dapagliflozin in insulin level concentration	Mean difference of insulin serum concentrations represented in µU/mL	12 weeks
Secondary	Impact of dapagliflozin in Hba1c	Mean difference of HbA1c represented in %	12 weeks
Secondary	Impact of dapagliflozin on patients weight	Mean difference of weight represented in kilograms	12 weeks
Secondary	Impact of dapagliflozin in blood pressure	Mean difference of systolic and diastolic blood pressure represented in mmHg	12 weeks
Secondary	Impact of dapagliflozin in waist circumference	Mean difference waist measured in centimeters	12 weeks