Sitagliptin and Kinetics of Triglyceride-rich Lipoproteins Apolipoprotein B48 and B100 in Patients With Type 2 Diabetes

NCT01334229 | Completed Phase 3 Results DMC

• 1 other identifier: IIS#39262
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

sitagliptin; diabetes; apolipoprotein B48 and B100

Outcome Measures

Primary Outcomes (1)

• Measurement of Apolipoprotein B48 and Apolipoprotein B100 Production Rates With Stable Isotope During Postprandial Period

  6 weeks

Secondary Outcomes (5)

• Measurement of Glucagon-like Peptide-1 by ELISA

  6 weeks

• Measurement of Glucose

  6 weeks

• Measurement of Insulin

  6 weeks

• Measurement of Apolipoprotein B48 and Apolipoprotein B100 Pool Sizes With Stable Isotope During Postprandial Period

  6 weeks

• Measurement of Apolipoprotein B48 and Apolipoprotein B100 Fractional Catabolic Rates With Stable Isotope During Postprandial Period

  6 weeks

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Sitagliptin 100 mg/d for 6 weeks

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Placebo for 6 weeks

Drug: Placebo

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg/d for 6 weeks

Also known as: Januvia

Sitagliptin

Placebo DRUG

Placebo for 6 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• 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 \< 15.0 mmol/L.
• Plasma triglyceride levels between 1.5 and 8.0 mmol/L (135 and 710 mg/dl) at screening and week -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 thyroid stimulating hormone 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.
• Patients taking any other hypoglycemic agent, other than metformin.
• Subjects will be excluded if they have cardiovascular disease (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 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.

Sponsors & Collaborators

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

Study Sites (1)

Laval University

Québec, Quebec, G1V 0A6, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Patrick Couture MD, PhD, FRCP
• 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: MD, PhD, FRCP

Study Record Dates

• First Submitted: April 11, 2011
• First Posted: April 13, 2011
• Study Start: April 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 4, 2016
• Results First Posted: September 10, 2014

Record last verified: 2016-03

Locations

CA (1)