Safety and Efficacy Study of Empagliflozin and Metformin for 24 Weeks in Treatment Naive Patients With Type 2 Diabetes

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Hyperglycemia; Diabetes Mellitus, Type 2

Treatments: Drug: Empagliflozin low dose qd; Drug: Empagliflozin high dose qd; Drug: Empagliflozin low dose bid; Drug: Metformin 500 mg bid; Drug: Metformin 1000 mg bid; Drug: Empagliflozin high dose bid

Study type: Interventional

Funder types: Industry

Identifiers

NCT01719003

1276.1

2010-021375-92 (EudraCT Number)

Details and patient eligibility

About

This study will investigate the efficacy and safety of two doses (high and low) of empagliflozin in combination with metformin (500 mg and 1000 mg) administered twice daily in patients with type 2 diabetes mellitus (T2DM). Study will compare four dose combinations of empagliflozin + metformin versus each individual component after 24 weeks of treatment.

Enrollment: 1,413 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of type 2 diabetes mellitus prior to informed consent
2. Male and female patients on diet and exercise regimen who are drug-naive, defined as absence of any oral antidiabetic therapy for 12 weeks prior to randomization
3. HbA1c >=7.5% and <= 12% (>=58.5 mmol/mol and <=107.7 mmol/mol)
4. Body Mass Index (BMI) <= 45 kg/m2 at screening

Exclusion criteria

1. Uncontrolled hyperglycemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second laboratory measurement (not on the same day)
2. Any antidiabetic drug within 12 weeks prior to randomization
3. Impaired renal function, defined as estimated creatinine clearance rate (eCCr) <60 ml/min (Cockcroft-Gault formula) as determined during screening and/or run-in period
4. Contraindications to metformin according to the local label

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

1,413 participants in 9 patient groups

Empagliflozin low dose qd

Experimental group

Description:

Empagliflozin low dose once daily

Treatment:

Drug: Empagliflozin low dose qd

Empagliflozin high dose qd

Experimental group

Description:

Empagliflozin high dose once daily

Treatment:

Drug: Empagliflozin high dose qd

OL empa high dose + met 1000 mg bid

Experimental group

Description:

Open label empagliflozin high dose split twice daily + metformin 1000 mg twice daily - Patients are no longer enrolled into this arm because of change in the inclusion criteria in protocol version 2.0 all patients are now enrolled into remaining double-blind arms. Patients already enrolled in the open-label arm according to protocol version 1.0 can complete the study.

Treatment:

Drug: Metformin 1000 mg bid

Drug: Metformin 1000 mg bid

Drug: Empagliflozin high dose bid

Drug: Metformin 1000 mg bid

Drug: Empagliflozin high dose bid

Drug: Empagliflozin high dose bid

Drug: Metformin 1000 mg bid

Empagliflozin low dose + met 500 mg bid

Experimental group

Description:

Empagliflozin low dose split twice daily + metformin 500 mg twice daily

Treatment:

Drug: Metformin 500 mg bid

Drug: Empagliflozin low dose bid

Drug: Metformin 500 mg bid

Drug: Empagliflozin low dose bid

Drug: Metformin 500 mg bid

Empagliflozin low dose + met 1000 mg bid

Experimental group

Description:

Empagliflozin low dose split twice daily + metformin 1000 mg twice daily

Treatment:

Drug: Metformin 1000 mg bid

Drug: Empagliflozin low dose bid

Drug: Metformin 1000 mg bid

Drug: Metformin 1000 mg bid

Drug: Empagliflozin low dose bid

Drug: Metformin 1000 mg bid

Empagliflozin high dose + met 500 mg bid

Experimental group

Description:

Empagliflozin high dose split twice daily + metformin 500 mg twice daily

Treatment:

Drug: Metformin 500 mg bid

Drug: Empagliflozin high dose bid

Drug: Metformin 500 mg bid

Drug: Empagliflozin high dose bid

Drug: Metformin 500 mg bid

Drug: Empagliflozin high dose bid

Empagliflozin high dose + met 1000mg bid

Experimental group

Description:

Empagliflozin high dose split twice daily + metformin 1000 mg twice daily

Treatment:

Drug: Metformin 1000 mg bid

Drug: Metformin 1000 mg bid

Drug: Empagliflozin high dose bid

Drug: Metformin 1000 mg bid

Drug: Empagliflozin high dose bid

Drug: Empagliflozin high dose bid

Drug: Metformin 1000 mg bid

Metformin 500 mg bid

Experimental group

Description:

Metformin 500 mg twice daily

Treatment:

Drug: Metformin 500 mg bid

Drug: Metformin 500 mg bid

Drug: Metformin 500 mg bid

Metformin 1000 mg bid

Experimental group

Description:

Metformin 1000 mg twice daily

Treatment:

Drug: Metformin 1000 mg bid

Drug: Metformin 1000 mg bid

Drug: Metformin 1000 mg bid

Drug: Metformin 1000 mg bid