Vildagliptin vs Sitagliptin add-on to Insulin - Impact on Glycemic Profile and Correlation of Hypoglycemic Episodes and Heart Function

Inclusion criteria

• 1. Written informed consent must be obtained before any assessment is performed.

• Ability to comply with all study requirements. 3. Patients with Type 2 diabetes treated with stable, once or twice daily doses (minimal dose of 0.3 unit/kg/day) of basal long-acting or intermediate-acting insulin alone or in pre-mixed combination with rapid-acting or short-acting insulin for at least 12 weeks prior to Visit 1. Stable is defined as ±10% of the Visit 1 dose during the previous 12 weeks.

• Patients receiving metformin must be on a stable dose of metformin (at least 1500 mg daily or a maximally tolerated dose) for at least 12 weeks prior to Visit 1. 5. HbA1c ≥7.5 to ≤ 9,0% at Visit 1 6. Known CV disease based on a documented history of one or more of pre-defined criteria 7. Age: ≥40 to ≤80 years at Visit 1

Exclusion criteria

• 1. FPG ≥ 270 mg/dL (15 mmol/L) at Visit 1. 2. Use of any of the following medications as assessed at Visit 1:

• rapid or short acting insulin except in pre-mixed formulations with intermediate or long-acting insulin; insulin administration more frequently than twice-daily, or total insulin dose < 0.3 unit/kg/day for the past 12 weeks
• use of any oral antidiabetic medication or GLP-1 analogues within the last 12 weeks, except metformin
• use of weight control products including weight-loss medications in the last 12 weeks.
• use of oral (≥7 consecutive days) or chronic parenteral or intra-articular corticosteroid treatment within the last 8 weeks. Inhaled or topical steroids without systemic effects will be allowed.
• treatment with growth hormone within the previous 6 months.
• treatment with any drug of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study.

• a history or evidence of any of the following at Visit 1:

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• acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including precoma and coma) within the past 6 months.
• current diagnosis of congestive heart failure (NYHA III or IV).
• myocardial infarction within the past 6 months.
• coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months.
• Stroke, transient ischemic attack, or reversible ischemic neurologic deficit within the past 6 months.
• unstable angina within the past 6 months.
• sustained and clinically relevant ventricular arrhythmia (patients with premature ventricular contractions if deemed not clinically significant may be enrolled).
• Patients with permanent atrial fibrillation or pacemaker.
• active substance abuse, alcohol abuse and history of alcohol-related diseases within the past 2 years.
• type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes (e.g. Cushing's syndrome or acromegaly-associated diabetes).
• malignancy of an organ system (other than localized basal cell carcinoma of the skin) treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• hepatic disorder defined as:

• acute or chronic liver disease, evidence of hepatitis, cirrhosis or portal hypertension.
• history of imaging abnormalities that suggest liver disease (except hepatic steatosis), such as portal hypertension, capsule scalloping, cirrhosis.
• acute infections which may affect blood glucose control within the past 4 weeks.

• any of the following significant laboratory abnormalities as assessed at Visit 1:

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• clinically significant increase or reduction in thyroid stimulating hormone (TSH) outside of the normal range.
• clinically significant renal dysfunction: glomerular filtration rate (GFR) <50 mL/min/1.73m2 (via MDRD formula).
• Patients on metformin with a GFR <60 mL/min/1.73m2 (via MDRD formula).
• alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Visit 1, confirmed by repeated measurements within 3 working days.
• total bilirubin > 2 x ULN and/or direct bilirubin > 1 x ULN confirmed by repeated measurements within 3 working days.
• positive Hepatitis B surface antigen (HBsAg).
• positive Hepatitis C virus (HCV) antibody test (anti-HCV).
• elevated fasting triglycerides (TGs) > 500mg/dL (5.65mmol/L), confirmed by a repeated measurements within 3 working days.
• clinically significant laboratory abnormalities which, in the opinion of the investigator, cause the patient to be considered inappropriate for inclusion in the study.

• any of the following electrocardiographic abnormalities at Visit 1:

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• second or third degree atrio-ventricular block.
• A QTc of > 440 ms.
• clinically significant electrocardiogram (ECG) abnormalities which, in the opinion of the investigator, may cause the patient to be considered inappropriate for inclusion in the study

Other protocol-defined inclusion/exclusion criteria may apply.