A Double-Blind, Randomized, Active-Comparator (Metformin) Controlled, Clinical Trial to Study the Efficacy and Safety of the Strategy to Start Patients With Type 2 Diabetes Mellitus on Janumet™ Compared to Metformin
A Double-Blind, Randomized, Active-Comparator (Metformin) Controlled, Clinical Trial to Study the Efficacy and Safety of the Strategy to Start Patients With Type 2 Diabetes Mellitus on Janumet™ Compared to Metformin
Comparison between the effectiveness of one anti-diabetic drug (Metformin, To combination of
 this drug and additional drug (Janufer), In the community setting.
This is a randomized, double-blind, active-comparator (metformin) controlled study in
 drug-naïve patients with T2DM who have an HbA1c ≥ 7.5%. The duration of the study is 55
 weeks, which will include a 1-week screening period (Visit 1 to Visit 2) and a 54 week
 double-blind, active treatment period. At Visit 2/Day 1 patients who meet all enrollment
 criteria will be randomized in a 1:1 ratio to one of two active treatment groups: 1. JANUMET™
 (fixed-dose combination sitagliptin/metformin) or 2. metformin. The starting fixed-dose
 combination of sitagliptin/metformin will be 50/500 mg administered twice-daily and then
 up-titrated to a dose of 50/1000 mg b.i.d. over 4 weeks. The starting dose of metformin will
 be 500 mg twice-daily and then up-titrated to a dose of 1000 mg b.i.d. over 4 weeks. Patients
 who can not tolerate JANUMET™ at a dose of at least 50/500 mg b.i.d. or metformin at a dose
 of at least 500 mg b.i.d. 6 weeks after randomization and throughout the study will be
 discontinued. During the double-blind treatment period patients will remain on the study
 medication, but investigators are allowed to add other antihyperglycemic agents to improve
 glycemic control as necessary. The investigator can schedule additional visits to initiate
 additional antihyperglycemic agents or monitor glycemic control at any time during the study
 period. There will be no fixed visit schedule, but 7 clinical visits are recommended. It is
 also recommended to perform the first visit on active treatment 6 weeks after randomization
 and after this visit to schedule visits every 3 months. All clinical and lab data can be
 obtained using the "Clalit health care information system".
Inclusion Criteria:

 -  All laboratory measurements are to be performed after an overnight fast ≥ 10 hours in
 duration. Patients with laboratory screening values/findings not meeting protocol
 inclusion criteria may, at the discretion of the investigator, have one repeat
 determination performed. If the repeat value satisfies the criterion they may continue
 in the screening process. Only the laboratory test not meeting inclusion should be
 repeated (not the entire panel).

 Exclusion Criteria:

 Glucose Metabolism and Therapy Criteria

 -  Patient has a history of type 1 diabetes mellitus or history of ketoacidosis. Patients
 Requiring Specific Treatments

 -  Patient has symptomatic hyperglycemia requiring immediate initiation of insulin
 therapy.

 -  Patient has a history of intolerance or hypersensitivity to metformin or sitagliptin
 or has any contraindication to use metformin.

 Concomitant Disease of Organs and Systems

 -  Patient has a medical history of active liver disease (excluding hepatic steatosis).

 -  Patient has severe active peripheral vascular disease (e.g., manifested by
 claudication with minimal activity, a non-healing ischemic ulcer, or disease which is
 likely to require intervention such as with bypass or angioplasty).

 -  Patient has unstable or acute congestive heart failure.

 -  Patient has a history of malignancy without documentation of remission/cure. Other
 Criteria

 -  Patient is pregnant, has a positive urine pregnancy test at Visit 1, is expecting to
 conceive within the projected duration of the study, or is breast feeding.

 Exclusion Criteria Based on Lab Abnormalities

 -  Patient has increased serum-creatinine and/or decreased estimated creatinine
 clearance.

 -  If screening labs are repeated, the last laboratory draw/result should be used for
 inclusion.§ Either elevated Creatinine or decreased estimated creatinine clearance
 lead to exclusion of the patient.

 -  Patients whose serum creatinine does not meet the exclusion criteria, but whose
 estimated creatinine clearance is <60 mL/min but ≥50 mL/min, may have a measured
 creatinine clearance (i.e., based upon a 24-hour urine collection). These patients may
 be eligible if their measured creatinine clearance is ≥60 mL/min.

 At Visit 2

 -  Patient has a site fingerstick glucose <130 mg/dL (7.2 mmol/L) or >320 mg/dL (17.8
 mmol/L).

 Note: If the patient meets this exclusion criterion AND the investigator believes that the
 value does not reflect the patient's recent glycemic control based upon recent SBGM values
 and/or the Visit 1 FPG value, the patient should not be excluded at this time. The current
 visit should be changed to an "Unscheduled visit" and the patient should be rescheduled for
 Visit 2. If, at the rescheduled Visit 2, the patient meets this exclusion criterion, the
 patient MUST be excluded.

 -  Patient has a positive urine pregnancy test.

 -  Patient developed a new medical condition, suffered a change in status of an
 established medical condition, developed a laboratory abnormality, or required a new
 treatment or medication between Visit 1 and Visit 2 which meets any previously
 described study exclusion criterion.