Effects of Sitagliptin on Postprandial Lipemia in Men With Type 2 Diabetes
Condition: Diabetes Mellitus; Postprandial Lipemia
MeSH terms: Diabetes Mellitus; Hyperlipidemias
Intervention: Sitagliptin; Placebo
Intervention description: Sitagliptin 100 mg/d for 6 weeks; Placebo for 6 weeks
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Diabetes mellitus; Postprandial; Hyperlipidemia; Atherosclerosis

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.
    

Eligibility 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.