Impact on Glycemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin Versus Metformin Alone

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran88 enrolled

Overview

This study will compare the effect of Dapagliflozin added to Metformin vs Metformin alone on blood sugar fluctuations of adults with a recent diagnosis of Type 2 Diabetes (T2D). The duration of the protocol will be 12 weeks. Continuous glucose monitoring will be measured before and at the end of the intervention. The questions this protocol will answer include: * Is there a difference in blood sugar fluctuations when Dapagliflozin is added to Metformin compared with Metformin alone in adults with type 2 Diabetes? * Does Dapagliflozin added to Metformin improve blood glucose control in patients with type 2 Diabetes?

This is an open-label randomized clinical trial aimed to compare the effect of Dapagliflozin added to Metformin vs Metformin alone on glycemic variability of adults with a recent diagnosis of type 2 Diabetes. The central hypothesis is that the addition of Dapagliflozin will lead to a statistically significant improvement in GV parameters compared to Metformin alone. A total of 88 adults aged 18-70 years with T2DM and HbA1c between 7.5% and 12% while on a stable dose of Metformin 2000 mg/day will be enrolled. Participants will be randomized in a 1:1 ratio to one of two treatment arms for a duration of 12 weeks. The primary objective is to compare the change from baseline to end-of-treatment in key glycemic variability indices derived from continuous glucose monitoring (CGM) (Mean Amplitude Glucose Excursions -MAGE, Time in Range), changes in HbA1c, fasting blood glucose, lipid profile, BMI, blood pressure, among others.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Interventions

Continuous glucose monitoringDIAGNOSTIC_TEST

Subjects enrolled will be randomized 1:1 to either receive a daily dosage of dapagliflozin 10 mg and 2000 mg metformin for 12 weeks or 2000 mg metformin. 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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 77 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects \> 18-77 years-old * Both Male and female * Hba1c ≥ 7.5 % and ≤12% * BMI \> 25 and \<45 kg/m2 * Type 2 diabetes diagnosis, drug-naive Exclusion Criteria: * Hba1c \> 12% * 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 enrollment, as assessed by the investigator * For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.

Outcomes

Primary Outcomes

ΔHbA1c

Difference between serum HbA1c before treatment (W0) and at the end of intervention (W12) expressed in percentage.

Time frame: 12 weeks

ΔMAGE

● Calculation of Mean Amplitude of Glucose Excursion (MAGE): * In the first step, all local maximum/minimum values are determined. * The next step is an evaluation of maximum/minimum pairs against the standard deviation (SD). * If the difference from minimum to maximum is greater than the SD, this variation from the mean measurement is retained. * If the local maximum/minimum is less than 1 SD, it is excluded from further calculations. * These channels are retained and summed to achieve the MAGE

Time frame: 12 weeks

Δweight

The difference between weight before the treatment period (W0) and the end of the intervention is calculated and expressed as delta for results interpretation.

Time frame: 12 weeks

ΔTIR %Target 70-180 mg/dL

Time in range is defined as the percentage of time that the patient's blood glucose is between 70-180 mg/dL.

Time frame: 12 weeks

Δinsulin

Delta insulin is defined as the difference in insulin plasma concentration before treatment (W0) and at the end of the intervention (W12).

Time frame: 12 weeks

Δsystolic Blood Pressure

It is defined as the difference in systolic blood pressure before treatment (W0) and after the end of intervention (W12)

Time frame: 12 weeks

ΔTriglycerides mg/dL

It is defined as the difference in triglycerides plasma concentration before and at the end of intervention (W12-W0)

Time frame: 12 weeks

Secondary Outcomes

ΔUric Acid

It is defined as the difference in plasma uric acid concentration before and at the end of intervention (W12-W0)

Time frame: 12 weeks

Impact on Glycemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin Versus Metformin Alone

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes