This study is intended to evaluate the pharmacodynamics, safety, and tolerability of LX4211 when administered concurrently with sitagliptin (Januvia®) in patients with Type 2 Diabetes Mellitus.

Inclusion Criteria:

• Adults aged 18 to 65 years of age
• History of Type 2 Diabetes Mellitus for at least 3 months prior to Screening, with HgbA1c values of 6.5 to 10.5% and C-peptide ≥1.0 ng/mL
• Body mass index (BMI) ≤45 kg/sq m
• Willing and able to self-monitor blood glucose
• Able to provide written informed consent

Exclusion Criteria:

• History of Type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic syndrome, or diabetes resulting from pancreatic disorder or secondary diabetes
• Current use of any blood glucose lowering agent other than metformin
• History of renal disease or clinically significant abnormal kidney function tests at Screening or Day -2
• Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or Day -2
• History of myocardial infarction, severe/unstable angina, or coronary revascularization procedure within 6 months of Day -2
• History of clinically significant cardiac arrhythmias within 1 year of Day -2
• Congestive heart failure and/or New York Heart Association (NYHA) class III or IV symptoms of heart failure
• Subjects with uncontrolled Stage 3 hypertension
• History of 2 or more emergency room visits, doctor's visits, or hospitalizations due to hypoglycemia within 6 months of Day -2
• History of alcohol or drug abuse within 12 months of Screening
• History of bowel resection > 20 cm, any malabsorptive disorder, severe gastroparesis, and GI procedure for the purpose of weight loss that would slow gastric emptying
• History of HIV or hepatitis C
• Major surgery within 3 months of Day -2 or any planned surgery during the study
• History of any active infection within 2 weeks of Day -2
• History of pancreatitis
• History of any malignancy within the last 5 years which would affect the diagnosis or assessment of LX4211 or sitagliptin
• History of any serious adverse reaction or hypersensitivity to LX4211 or sitagliptin
• Presence of any clinically significant physical, laboratory, or ECG findings or any concurrent condition at Screening that may interfere with the study in the opinion of the investigator
• Triglycerides > 1000 mg/dL at Screening or Day -2
• Donation or loss of >400 mL of blood or blood product within 8 weeks prior to Day -2
• Use of any tobacco product for the duration of study participation
• Use of corticosteroids within 2 weeks of Day 1
• Use of digoxin or warfarin within 2 weeks prior to Screening