Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes

• Status: Completed
• Trial end date: 2018-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this study is to examine whether sitagliptin, an agent which enhances the action of hormones that control the release of insulin and is already in clinical use for type 2 diabetes, might also improve functional exercise capacity.

Specific aims:

1. To test whether sitagliptin will improve functional exercise capacity in persons with type 2 diabetes compared to glimepiride.

1a. The primary outcome will be peak oxygen consumption (VO2peak) and oxygen uptake kinetics (VO2 kinetics).

1b. Secondary outcomes include cardiac function, endothelial function and tissue oxygen saturation (STO2) as well as health-related quality of life.

2. To evaluate the impact of sitagliptin on muscle mitochondrial function 2a. The primary outcome to address this aim will be 31P measurements (phosphocreatine, free inorganic phosphate, adenosine triphosphate peaks, adenosine diphosphate and pH)

Impact: Novel approaches are needed to decrease excess cardiovascular morbidity and mortality in diabetes. Diabetes impairs cardiovascular fitness and thereby mortality. A demonstration that sitagliptin improves cardiovascular fitness, (and possibly mitochondrial function) will provide important new data pertinent to the management of diabetes and pre-diabetes.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Glimepiride; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

1. Female subjects may be pre, peri or post-menopausal.

2. People who do not participate in a regular exercise program (> one bout of exercise per week).

3. Presence of type 2 diabetes will be documented by chart review that will confirm the diagnosis as well as the presence of treatment for diabetes.

4. Persons with type 2 diabetes will be accepted for study only if they have total glycosylated hemoglobin levels (HbA1C) between 7 and 9.5% (adequate control) on therapy.

5. Persons who are taking metformin 500-2000 mg/day only to control their T2D, but are not taking any other diabetes medication in addition to or instead of metformin.

6. Persons not taking medication to control diabetes.

Exclusion Criteria:

1. Females of childbearing potential who are pregnant, planning to become pregnant or breastfeeding.

2. Persons will be excluded if they have evidence of ischemic heart disease by history or abnormal resting or exercise electrocardiogram (EKG) (> 1 mm ST segment depression), regional wall motion abnormalities, left ventricular systolic dysfunction or significant valvular disease.

3. Persons with angina or any other cardiac or pulmonary symptoms potentially limiting exercise performance.

4. Presence of systolic blood pressure >190 at rest or >250 with exercise or diastolic pressure >95 at rest or >115 with exercise.

5. Subjects who have peripheral arterial disease.

6. Subjects with proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl, suggestive of renal disease.

7. Persons with liver function impairment defined as elevated liver function tests three times the upper limit.

8. Persons with a history of pancreatitis.

9. Subjects more than 140% of ideal body weight.

10. Patients on insulin therapy will not be included.

11. Current smokers will not be accepted for study since smoking can impair cardiovascular exercise performance but people who have quit smoking for at least 1year will be accepted for study.

12. Persons with autonomic dysfunction (>20 mm fall in upright blood pressure without a change in heart rate) will be excluded.

13. Diabetic persons with clinically evident distal symmetrical neuropathy will be excluded from further study, because of possible effects on exercise performance, by evaluation of symptoms (numbness, paresthesia) and signs (elicited by vibration, pinprick, light touch, ankle jerks).

14. Persons with diabetic ketoacidosis.

15. Persons with a serious hypersensitivity to sitagliptin, sulfonylureas or sulfonamides.

16. Inability to walk or ride a bike unassisted for a continuous 5 minutes.

17. Subjects will be excluded if they have any implanted metal in their body.

18. Subjects currently being treated with Digoxin.