Clinical trial NCT04090580: Impact on Glycemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin Versus Metformin Alone
Official title: Impact on Glycemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin Versus Metformin Alone: A Randomized Open Label Clinical Study. The MAGNNIFY Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: dapagliflozin
glycemic variability
MAGE
DIABETES MELLITUS
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2019-09-16
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 77
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Evaluation of efficacy between Dapagliflozin with Metformin (Intervention) vs Metformin alone (Standard of care)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ΔHbA1c
timeFrame: 12 weeks
measure: ΔMAGE
timeFrame: 12 weeks
measure: Δweight
timeFrame: 12 weeks
measure: ΔTIR %Target 70-180 mg/dL
timeFrame: 12 weeks
measure: Δinsulin
timeFrame: 12 weeks
measure: Δsystolic Blood Pressure
timeFrame: 12 weeks
measure: ΔTriglycerides mg/dL
timeFrame: 12 weeks
Secondary outcomes:
measure: ΔUric Acid
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán ''INCMNSZ''
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Miguel Angel Gomez Samano, MD
role: PRINCIPAL_INVESTIGATOR
References: