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

NCT00660075 | Completed Phase 3 Results DMC

• 1 other identifier: SITA001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus; Postprandial Lipemia

Keywords

Diabetes mellitus; Postprandial; Hyperlipidemia; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Measurement of the Area Under the Curve of Plasma Triglycerides (TG) Levels During Postprandial Period (Time 0,2,4,6,8 Hours)

  At the end of the two 6-week interventions

Study Arms (2)

1

EXPERIMENTAL

Sitagliptin 100 mg/d for 6 weeks

Drug: Sitagliptin

2

PLACEBO COMPARATOR

Placebo for 6 weeks

Drug: Placebo

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg/d for 6 weeks

1

Placebo DRUG

Placebo for 6 weeks

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Laval University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Laval University Medical Center

Québec, Quebec, G1V 4G2, Canada

Location

Related Publications (1)

• Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism. 2014 Sep;63(9):1141-8. doi: 10.1016/j.metabol.2014.06.004. Epub 2014 Jun 14.

  PMID: 25034387 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Hyperlipidemias; Atherosclerosis

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Dyslipidemias; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Patrick Couture
• Organization: Laval University

patrick.couture@crchul.ulaval.ca

418-654-2106

Study Officials

• Patrick Couture, MD, PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Médecin

Study Record Dates

• First Submitted: April 14, 2008
• First Posted: April 17, 2008
• Study Start: February 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: April 1, 2009
• Last Updated: December 11, 2012
• Results First Posted: December 11, 2012

Record last verified: 2012-11

Locations

CA (1)