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

Mayo Clinic

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Ursodiol

Study type: Interventional

Funder types: Other

Identifiers

NCT02033876

13-004908

Details and patient eligibility

About

This study will evaluate whether bile acids are able to increase insulin sensitivity and enhance glycemic control in T2DM patients, as well as exploring the mechanisms that enhance glycemic control. These observations will provide the preliminary data for proposing future therapeutic as well as further mechanistic studies of the role of bile acids in the control of glycemia in T2DM.

Full description

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

Hypothesis: The bile acid, ursodeoxycholic acid (UDCA) in delayed (ileocolonic)-release formulation, stimulates bile acid membrane receptor (TGR-5) and farnesol X (FXR) receptors in the ileum and colon, increasing the secretion of Fibroblast growth factor 19 (FGF-19), GLP-1, oxyntomodulin (OXM), and Peptide (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 gastric emptying (GE) of liquids.

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

Enrollment: 24 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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24 participants in 2 patient groups, including a placebo group

Ursodiol

Experimental group

Description:

Ursodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily

Treatment:

Drug: Ursodiol

Placebo

Placebo Comparator group

Description:

matching placebo capsules to be taken twice daily

Treatment:

Drug: Ursodiol