Effects of DPP-4 Inhibition on Triglycerides

Oregon Health & Science University (OHSU)

Status and phase

Suspended

Phase 4

Conditions

Hypertriglyceridemia

Type 2 Diabetes

Treatments

Drug: Saxagliptin

Study type

Interventional

Funder types

Other

Identifiers

NCT01527747

CV181-142

Details and patient eligibility

About

The purpose of this study is to test the effects of saxagliptin, a treatment for diabetes, on fasting and post-meal blood triglyceride (blood fat) levels.

Full description

This study is designed to help us understand the effects of DPP-4 inhibition on triglyceride levels before and after eating.

Enrollment

15 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Willing to provide signed written informed consent
Men and women aged 18-80 years
Type 2 diabetes (as defined by the ADA - see reference 18)
Baseline HgbA1c between 6.5% and 8%; HgbA1c 7.5-8.0% among subjects taking sulfonylureas
Baseline plasma triglyceride concentration between 200 and 700 mg/dl
Stable diabetes medication regimen for at least 12 weeks prior to study entry
Taking a statin for at least 8 weeks, unless statin therapy is contraindicated or intolerable
Treatment with other lipid-lowering medications only if the dose has been stable for > 8 weeks.
Non-smoker
Body mass index < 45.0 kg/m2
BP < 140/85
Normal serum TSH and free T4 concentrations (hypothyroid subjects taking a stable replacement dose of levothyroxine will be allowed if they are biochemically euthyroid)
Subjects will otherwise be healthy
Women of child-bearing potential must be willing to use reliable contraception, as defined by our IRB, throughout the study (There are currently no FDA recommended restrictions on the use of saxagliptin in sexually active men, or requirements for contraception in their wives or sexual partners)
Able and willing to complete study procedures

Exclusion criteria

Transaminase concentrations > 2 times the ULN. (Mild elevations of AST and ALT will be allowed up to 2x ULN at baseline if there is no evidence of viral hepatitis or intrinsic liver disease. Since many of these subjects may have some degree of hepatic steatosis, a key intervention is the implementation of treatment to lower glucose and triglycerides)
Estimated creatinine clearance < 60 ml/min
Microalbumin-creatinine ratio > 120
Alcohol consumption > 1 drink daily in women and > 2 drinks daily in men
Pancreatitis within the preceding 6 months
Type 1 diabetes
History of diabetic ketoacidosis (DKA)
Cardiovascular disease (CAD, stroke, PVD)
Known human immunodeficiency virus (HIV) infection
Viral hepatitis
Pregnancy or lactation
A current diagnosis of active non-dermatologic cancer
Other life-threatening illness
History of small bowel resection or gastric bypass surgery
Use of glucocorticoid medications, beta blockers, thiazide diuretics, excess alcohol intake (beta-blockers and thiazide diuretic will be allowed, if necessary, if the dose has been stable for > 12 weeks prior to study entry and the dose will remain stable throughout the study. Complete exclusion of these drugs would exclude a substantial proportion of diabetic patients)
Use of systemic cytochrome P450 3A4 (CYP 3A4/5) inhibitors such as ketaconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir and telithromycin.
Current enrollment in another research study or use of any investigational drug within 90 days of study entry
Other medical conditions that may interfere with participation in the study, in the opinion of the investigator