Safety and Efficacy of the Combination of Empagliflozin and Linagliptin Compared to Linagliptin Alone Over 24 Weeks in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial compare the use of two different doses of Empagliflozin to placebo, in T2DM patients on 16 wks linagliptin treatment and metformin background therapy.

Official Title
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A Phase III, Randomised, Double-blind, Parallel Group, 24 Week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg and 25 mg Compared to Placebo, All Administered as Oral Fixed Dose Combinations With Linagliptin 5 mg, in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16 Weeks Treatment With Linagliptin 5 mg Once Daily on Metformin Background Therapy.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Empagliflozin + Linagliptin
* Drug: Empagliflozin + Linagliptin
* Drug: Empagliflozin + Linagliptin
* Drug: Empaglifozin placebo + Linagliptin placebo
* Drug: Empagliflozin + Linagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of type 2 diabetes mellitus. Male and female patients on diet and exercise regimen, pre-treated with immediate release metformin for at least 12 weeks, and patients should be on a dose higher or equal to 1500 mg/day of metformin, or maximum tolerated dose, or maximum dose as per local label. HbA1c higher or equal to 8.0% and lower or equal to 10.5% at screening visit. Age 18 years or more at screening. Body Mass Index lower or equal to 45 kg/m2 at screening visit. Signed and dated written informed consent. Exclusion criteria: Uncontrolled hyperglycemia with glucose level above 270 mg/dl (above 15 mmol/dl) after an overnight fast. Use of any other antidiabetic drug (except metformin background therapy). Acute coronary syndrome, stroke or TIA within 3 months prior to informed consent. Indication of liver disease. Impaired renal function. Gastrointestinal surgery. Treatment with anti-obesity drugs within 3 months prior to screening, or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight. Current treatment with systemic steroids at time of informed consent or uncontrolled endocrine disorder except type 2 diabetes mellitus.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Linagliptin<br>5 mg once daily | Drug: Linagliptin<br>* tablet<br>Drug: Empaglifozin placebo + Linagliptin placebo<br>* Matching Empaglifozin + Linagliptin low dose<br>|
| Experimental: Empaglifozin + Linagliptin low dose<br>1 tablet once daily | Drug: Empagliflozin + Linagliptin<br>* Fixed dose combination.<br>Drug: Empagliflozin + Linagliptin<br>* Fixed dose combination<br>|
| Experimental: Empagliflozin + Linagliptin high dose<br>1 tablet once daily | Drug: Empagliflozin + Linagliptin<br>* Fixed dose combination<br>Drug: Empagliflozin + Linagliptin<br>* Fixed dose combination.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Change From Baseline After 24 Weeks Double-blind Randomized Treatment | Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double-blind trial medication. Baseline was defined as the last observation before the first intake of any double-blind randomised trial medication. The term 'baseline' was not used to refer to measurements before the administration of open-label medication. | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose (FPG) Change From Baseline After 24 Weeks of Double-blind Treatment. | Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication. | Baseline and 24 weeks | 
| Body Weight Change From Baseline After 24 Weeks of Double-blind Treatment | Change from baseline Body weight after 24 weeks of treatment with double-blind trial medication. | Baseline and 24 weeks |