Phase 3
N=22
Sitagliptin and Kinetics of Triglyceride-rich Lipoproteins Apolipoprotein B48 and B100 in Patients With Type 2 Diabetes
Type 2 Diabetes Mellitus
Bottom Line
View on ClinicalTrials.gov: NCT01334229 ↗Enrolled (actual)
22
Serious AEs
0.0%
Results posted
Sep 2014
Primary outcome: Primary: Measurement of Apolipoprotein B48 and Apolipoprotein B100 Production Rates With Stable Isotope During Postprandial Period — 2.1; 2.5; 27.5; 30.3 mg/kg/day
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sitagliptin (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Laval University
- Primary completion
- Mar 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Measurement of Apolipoprotein B48 and Apolipoprotein B100 Production Rates With Stable Isotope During Postprandial Period |
2.1; 2.5; 27.5; 30.3 | — |
| SECONDARY Measurement of Glucagon-like Peptide-1 by ELISA |
5.6; 3.1 | — |
| SECONDARY Measurement of Glucose |
7.7; 8.9 | — |
| SECONDARY Measurement of Insulin |
161.1; 179.5 | — |
| SECONDARY Measurement of Apolipoprotein B48 and Apolipoprotein B100 Pool Sizes With Stable Isotope During Postprandial Period |
38.4; 48.5; 488.0; 537.8 | — |
| SECONDARY Measurement of Apolipoprotein B48 and Apolipoprotein B100 Fractional Catabolic Rates With Stable Isotope During Postprandial Period |
6.2; 6.3; 5.9; 5.9 | — |
Summary
Sitagliptin is a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-IV), 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 [13]. Although clinical studies to date indicate that fasting lipid levels are minimally affected by DPP-IV inhibitor treatment [14-16], animal studies suggested that DPP-IV inhibition reduce intestinal triglycerides (TG) absorption and apolipoprotein (apo) production [17] and increased chylomicron catabolism [18]. Interestingly, a recent study supporting this hypothesis showed that vildagliptin therapy was able to reduce postprandial intestinal triglyceride-rich lipoproteins (TRL) particles in patients with type 2 diabetes [19]. Recently, our group has reported that sitagliptin treatment significantly reduced plasma apo B-48 and TG concentrations in the postprandial state. Moreover, animal studies showed that sitagliptin decreased intestinal secretion of intestinal apo B-48, mainly by increasing level of glucagon-like peptide (GLP)-1 [20]. Therefore, the present study was designed to examine the effects of sitagliptin on the kinetics of TRL apo B-48 and in patients with type 2 diabetes. A possible reduction in postprandial atherogenic TRL apo B-48-containing lipoprotein 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
- Males 18 to 65 years of age.
- Post-menopausal women under age 65 on stable medical therapy for 6 months before the study (the patient should have demonstrated stable lipid panels)
- Women should not be on hormone replacement therapy (no recent starting or stopping)
- Type 2 diabetes as defined by the American Diabetes Association.
- Non-smoker.
- Body mass index between 25.0 and 40.0 kg/m2.
- Baseline glycated hemoglobin A1c (HbA1c) between 6.5 and 8.5%.
- Baseline fasting plasma glucose 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 aspartate aminotransferase or alanine aminotransferase >2 x upper limit of the laboratory reference range will be excluded.
- Subjects with coagulopathy (prothrombin time or partial thromboplastin time at Visit 1 >1.5 times control).
- Subjects with hemoglobin >2 x the lower limit of the laboratory reference range will be excluded.
- 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 New York Heart Association (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.
Data sourced from ClinicalTrials.gov (NCT01334229). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.