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

Phase 3

Completed

Lead Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Brief Summary: 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?

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Daily dosage of metformin	Continuous glucose monitoring	Subjects enrolled will be randomized 1:1 to either receive a daily dosage of 2000 mg metformin for 12 weeks
Daily dosage of dapagliflozin and metformin	Continuous glucose monitoring	Subjects enrolled will be randomized 1:1 to either receive a daily dosage of 10 mg dapagliflozin and 2000 mg metformin for 12 weeks

Primary Outcome Measures

Name	Time	Method
ΔHbA1c	12 weeks	Difference between serum HbA1c before treatment (W0) and at the end of intervention (W12) expressed in percentage.
ΔMAGE	12 weeks	● 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
ΔTIR %Target 70-180 mg/dL	12 weeks	Time in range is defined as the percentage of time that the patient's blood glucose is between 70-180 mg/dL.
Δweight	12 weeks	The difference between weight before the treatment period (W0) and the end of the intervention is calculated and expressed as delta for results interpretation.
Δinsulin	12 weeks	Delta insulin is defined as the difference in insulin plasma concentration before treatment (W0) and at the end of the intervention (W12).
Δsystolic Blood Pressure	12 weeks	It is defined as the difference in systolic blood pressure before treatment (W0) and after the end of intervention (W12)
ΔTriglycerides mg/dL	12 weeks	It is defined as the difference in triglycerides plasma concentration before and at the end of intervention (W12-W0)