Effects of Sitagliptin on Postprandial Lipemia in Men With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Patrick Couture, Laval University
ClinicalTrials.gov Identifier:
NCT00660075
First received: April 14, 2008
Last updated: November 13, 2012
Last verified: November 2012
  Purpose

Sitagliptin is a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-4), and has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes mainly through incretin hormone-mediated improvements in islet function. Although clinical studies to date indicate that fasting lipid levels are minimally affected by DPP-4 inhibitor treatment, animal studies suggested that DPP-4 inhibition reduce intestinal triglyceride (TG) absorption and apolipoprotein production and increased chylomicron catabolism. Therefore, the present study was designed to examine the effects of sitagliptin on postprandial lipemia in patients with type 2 diabetes. A possible reduction in postprandial atherogenic triglyceride-rich lipoproteins (TRL) levels by sitagliptin would add to therapeutic utility of this DPP-4 inhibitor and suggest the potential to reduce cardiovascular risk in patients with type 2 diabetes.


Condition Intervention Phase
Diabetes Mellitus
Postprandial Lipemia
Drug: Sitagliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Evaluate The Effects of Sitagliptin on Postprandial Plasma Lipoprotein Concentrations in Men With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Measurement of the Area Under the Curve of Plasma Triglycerides (TG) Levels During Postprandial Period (Time 0,2,4,6,8 Hours) [ Time Frame: At the end of the two 6-week interventions ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: February 2008
Study Completion Date: April 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Sitagliptin 100 mg/d for 6 weeks
Drug: Sitagliptin
Sitagliptin 100 mg/d for 6 weeks
Placebo Comparator: 2
Placebo for 6 weeks
Drug: Placebo
Placebo for 6 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes as defined by the American Diabetes Association;
  • Non-smoker;
  • Body mass index between 25.0 and 40.0 kg/m2;
  • Baseline HbA1c between 6.5 and 8.5%;
  • Baseline fasting plasma glucose < 15.0 mmol/L;
  • Plasma triglyceride levels between 1.5 and 8.0 mmol/L (135 and 710 mg/dl) at week and -4;
  • Patients having received stable doses of metformin for at least 3 months before randomization;
  • Subjects must be willing to give written informed consent and able to adhere to dosing schedule, visit schedule and phone follow-up assessment;
  • Patients should be otherwise generally healthy, without elevations in hepatic transaminases or abnormal renal function or coagulation;
  • Patients having normal TSH at screening.

Exclusion Criteria:

  • Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be excluded;
  • Patients with type 1 diabetes, secondary form of diabetes or acute metabolic diabetic complications will be excluded;
  • Patients having received or being treated with insulin or a thiazolidinedione within the past 6 months will be excluded;
  • Subjects will be excluded if they have cardiovascular disease (CVD) (coronary heart disease, cerebrovascular disease or peripheral arterial disease) or if they are taking other medications known to affect lipoprotein metabolism (e.g. steroids, beta blockers, thiazide diuretics, lipid lowering agents, significant alcohol intake etc.);
  • Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study;
  • Individuals with a history of mental instability, drug or alcohol abuse or individuals who have been treated or are being treated for severe psychiatric illness that, in the opinion of the investigator, may interfere with optimal participation in the study;
  • History of alcohol or drug abuse within the past 2 years. Patients must not take alcohol during the study;
  • Disorders of the hematologic, digestive, or central nervous systems, including cerebrovascular disease and degenerative disease, that would limit study evaluation or participation;
  • Known impairment of renal function (serum creatinine levels > 1.7 mg/dL for men), dysproteinemia, nephrotic syndrome, or other renal disease (24-hour urinary protein ≥3 ± 1 g);
  • Active or chronic hepatobiliary or hepatic disease. In addition, patients with AST or ALT >2 x upper limit of the laboratory reference range will be excluded;
  • Subjects with coagulopathy (prothrombin time [PT] or partial thromboplastin time [PTT] at Visit 1 >1.5 times control;
  • Patients who are known to have tested positive for human immunodeficiency virus (HIV);
  • Patients who are currently enrolled in another clinical study;
  • Patients who have used any investigational drug within 30 days of the first clinic visit;
  • Congestive heart failure NYHA Class III or IV. Uncontrolled cardiac arrhythmias within 3 months of study entry;
  • Uncontrolled diabetes mellitus (HbA1c>8.5%) or other endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid subjects on replacement doses of thyroid hormone are eligible for enrollment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660075

Locations
Canada, Quebec
Laval University Medical Center
Quebec City, Quebec, Canada, G1V 4G2
Sponsors and Collaborators
Laval University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Patrick Couture, MD, PhD Laval University
  More Information

No publications provided

Responsible Party: Patrick Couture, Médecin, Laval University
ClinicalTrials.gov Identifier: NCT00660075     History of Changes
Other Study ID Numbers: SITA001
Study First Received: April 14, 2008
Results First Received: May 18, 2011
Last Updated: November 13, 2012
Health Authority: Canada: Health Canada

Keywords provided by Laval University:
Diabetes mellitus
Postprandial
Hyperlipidemia
Atherosclerosis

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperlipidemias
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dyslipidemias
Lipid Metabolism Disorders
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014