The Effects of Co-admin of Colesevelam and Sitagliptin on Glucose Metabolism in Subjects With Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Effects of Co-administration of Colesevelam and Sitagliptin on Glucose Metabolism in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01092663
• Other study ID #: KM-29
• Status: Completed
• Phase: N/A
• First received: March 23, 2010
• Last updated: January 15, 2013
• Start date: March 2010
• Est. completion date: July 2011

Study information

• Verified date: January 2013
• Source: KineMed
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This study will assess the effects of colesevelam, alone or in combination with sitagliptin, on glucose metabolism in subjects with T2DM inadequately controlled by diet and exercise

Description:

The hypothesis is that co-administrationof colesevelam plus sitagliptin results in a greater reduction in HbA1c compared to colesevelam HCl treatment by

1. improving the effects of colesevelam on fasting glucose metabolism

2. improving the effects of colsevelam on postprandial glucose metabolism

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male or Female

• Females of childbearing potential are on approved birth control method

• Negative pregnancy testing for females of childbearing potential

• Previously diagnosed or newly diagnosed with T2DM drug naïve subjects

• HbA1c: 6.7-10%

• Age 18 - 80 years

• BMI = 18.5 kg/m2 and = 40 kg/m2

• Fasting serum glucose < 300 mg/dL

• Normal liver function, normal thyroid function, no history of liver, biliary or intestinal disease

• Normal TSH

• On stable diet and exercise routine for at least 4 weeks prior to screening

• Has had a stable weight (+/-5%) for =3 months before screening

Exclusion Criteria:

• A history of type 1 diabetes mellitus or history of diabetic ketoacidosis

• History of chronic (required daily for > 2 months) use of insulin therapy

• Treatment with blood pressure lowering therapy that has not been stable for three months before screening

• Treatment with lipid lowering medication other than statins

• Treatment with statins that has not been stable for three months before screening

• Treatment with a DPP-4 inhibitor or and GLP1 agonists at any time

• Treatment with a thiazolidinedione (TZD) within the last 6 months of screening

• History of an allergic or toxic reaction to sitagliptin or colesevelam

• History of dysphagia, swallowing disorders, bowel obstruction, intestinal motility disorder, and gastrointestinal disorders

• History of major gastrointestinal surgery

• History of kidney problems

• Fasting plasma triglycerides > 300 mg/dL

• Serum LDL-C <60 mg/dL

• Positive toxicology test

• Known hypersensitivity to colesevelam HCl or sitagliptin.

• Any contraindications to a study medication (colesevelam HCl or sitagliptin).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Colesevelam HCl
Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks.
• Sitagliptin
Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks.

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami	Miami	Florida
United States	Healthcare Discoveries, LLC d/b/a ICON Development Solutions	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
KineMed

Country where clinical trial is conducted

United States, 

References & Publications (7)

Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7. — View Citation

Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008 Oct 13;168(18):1975-83. doi: 10.1001/archinte.168.18.1975. — View Citation

Fonseca VA, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care. 2008 Aug;31(8):1479-84. doi: 10.2337/dc08-0283. Epub 2008 May 5. — View Citation

Goldberg RB, Fonseca VA, Truitt KE, Jones MR. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control receiving insulin-based therapy. Arch Intern Med. 2008 Jul 28;168(14):1531-40. doi: 10.1001/archinte.168.14.1531. — View Citation

Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007 Aug;30(8):1979-87. Epub 2007 May 7. Erratum in: Diabetes Care. 2008 Aug;31(8):1713. — View Citation

Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP; Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007 Mar;9(2):194-205. — View Citation

Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clin Ther. 2007 Jan;29(1):74-83. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemoglobin A1C	Change from baseline in hemoglobin A1C after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments	Baseline and 12 weeks	No
Primary	Fasting Plasma Glucose	Change from baseline in fasting plasma glucose concentrations after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments.	Baseline and 12 weeks	Yes
Primary	Fasting Endogenous Glucose Production	Change from baseline in fasting endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment	baseline and 12 weeks	No
Primary	Fasting Gluconeogenesis	Change from baseline in fasting gluconeogenesis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment	baseline and 12 weeks	No
Primary	Fasting Glycogenolysis	Change from baseline in fasting glycogenolysis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment	baseline and 12 weeks	No
Primary	Fasting Plasma Glucose Clearance	Change from baseline in fasting plasma glucose clearance after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments.	baseline and 12 weeks	No
Primary	Appearance Rate of Oral Glucose	Change from baseline in appearance rate of oral glucose after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments	baseline and 12 weeks	No
Primary	Postprandial Endogenous Glucose Production	Change from baseline in postprandial endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments; Mean value was calculated using all results measured between 10 and 300 min post meal.	baseline and 12 weeks	No
Primary	Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC)	Change from baseline in postprandial rate of total glucose disposal (AUC) after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments; AUC was calculated by the trapezoid method using all results measured between 0 and 300 min during the meal tolerance test.	baseline and 12 weeks	No
Primary	Whole-body Glycolytic Disposal of Oral Glucose	Change in baseline in whole-body glycolytic disposal of oral glucose after 12 weeks of colesevelam alone or colesevelam plus glucose treatments	baseline and 12 weeks	No
Primary	Postprandial Glucose (AUC)	Comparison between baseline and 12 weeks values of postrandial glucose (AUC).	Baseline and 12 weeks	No
Secondary	Fasting Plasma C-peptide	To evaluate the effect of treatments on plamsa C-peptide concentrations.	Baseline and 12 weeks	No
Secondary	Fasting Plamsa Glucagon	To evaluate the effect of treatments on plasma glucagon concentrations.	Baseline and 12 weeks	No
Secondary	Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1)	To evaluate the effect of treatments on plasma GLP-1 concentrations.	Baseline and 12 weeks	No
Secondary	Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP)	To evaluate the effect of treatments on plasma Glucose-dependent Insulinotropic Peptide (GIP) concentrations.	Baseline and 12 weeks	No
Secondary	Fasting Insulin	To evaluate the effect of treatments on fasting insulin concentrations	Baseline and 12 weeks	No
Secondary	Postprandial Insulin (AUC)	To evaluate the effect of treatments on postprandial insulin (AUC)	Baseline and 12 weeks	No
Secondary	Postprandial C-peptide (AUC)	To evaluate the effect of treatments on postprandial C-peptide (AUC)	Baseline and 12 weeks	No
Secondary	Postprandial Active GLP-1 (AUC)	To evaluate the effects of treatments on postprandial active GLP-1 (AUC)	Baseline and 12 weeks	No
Secondary	Postprandial Total GIP (AUC)	To evaluate the effects of treatment on postprandial total GIP (AUC)	Baseline and 12 weeks	No
Secondary	Postprandial Glucagon (AUC)	To evaluate the effects of treatment on postprandial glucagon (AUC)	Baseline and 12 weeks	No

External Links

•   Ethics and Compliance
•   link to completed trials