Ursodiol on Insulin Sensitivity, Gastric Emptying and Body Weight With Type 2 Diabetes on Metformin

Background: Intra-jejunal administration of bile acids improves insulin sensitivity.

Hypothesis: The bile acid, ursodeoxycholic acid (UDCA) in delayed (ileocolonic)-release
formulation, stimulates TGR-5 and FXR receptors in the ileum and colon, increasing the
secretion of FGF-19, GLP-1, oxyntomodulin (OXM), and PYY3-36, improving insulin sensitivity
and inducing weight loss.

Aim: To study the effect of an ileocolonic formulation of UDCA on insulin sensitivity,
postprandial plasma glycemia and incretin levels, gastric emptying and body weight in
overweight or obese type 2 diabetic subjects on monotherapy with metformin.

Study design: This is a single center, placebo-controlled, parallel group, single dose
randomized controlled trial to study the effect of delayed (ileocolonic)-release UDCA 600 mg
twice daily on insulin sensitivity, gastric emptying of liquids and solids (measured by
scintigraphy)and weight loss in overweight or obese type 2 diabetic subjects. Participants
will be receiving monotherapy with metformin. Blood samples will be collected at defined
times to measure glycemia and the incretin (GLP-1, OXM, PYY3-36) fasting levels and responses
to the meal.

Anticipated Results: In comparison with placebo, UDCA will increase insulin sensitivity,
enhance glycemic control, increase postprandial incretins, and delay GE of liquids.

Significance: This study will prove that ileocolonic-release UDCA enhances glycemic control
in T2DM patients.

Overweight or Obese subjects with BMI> 25 Kg/m2 with Type 2 Diabetes mellitus on Metformin,
receiving standard of care for Type 2 DM. Otherwise individuals who are not currently on
treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological,
neurological, endocrine (other than T2DM) and unstable psychiatric disease.

Men or women. Women of childbearing potential will have a negative pregnancy test before
initiation of medication.