SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2

The inhibition of the renal (kidney) SGLT2 transporter has proven to be an effective
therapeutic intervention to reduce plasma glucose levels (amount of glucose found in the
liquid part of blood) and HbA1c.

In this study, the investigators hope to define the role of increased plasma glucagon,
decline in plasma insulin, and fall in plasma glucose concentration. The investigators will
examine whether the signal for the increase in EGP (endogenous glucose production) caused by
glucosuria (an excess of sugar in the urine, typically associated with diabetes) is mediated
via the decrease in plasma glucose and insulin concentrations, or by the increase in plasma
glucagon concentration.

Inclusion Criteria:

- T2DM subjects

- 18 - 70 yrs old

- BMI = 25-45 kg/m2

- Must be on a stable dose (more than 3 months) of monotherapy or combination therapy
with metformin and/or a sulfonylurea

- HbA1c <10.0%

- Stable body weight (± 3 lbs) over preceding 3 months

- Do not participate in excessively heavy exercise

Exclusion Criteria:

- Subjects taking drugs known to affect glucose metabolism (other than metformin and
sulfonylurea)

- Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine
>1.4 females or >1.5 males, or 24-hour urine albumin excretion > 300 mg