Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes

NCT01951339 | Completed Results

• 1 other identifier: 13-2015
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes; Cardiovascular Disease

Keywords

diabetes; type 2 diabetes; exercise; echo; heart; sitagliptin; glimepiride; cardiovascular

Outcome Measures

Primary Outcomes (7)

• Peak Oxygen Consumption (VO2peak).

  Subjects' peak oxygen consumption will be tested on a stationary bike before and after 3 months of study medication.

  Pre-intervention (Baseline) and post-intervention (3 months)

• Changes From Baseline in 31P Measurement: Phosphocreatine Time Constant

  Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment

  Pre-intervention (Baseline) and post-intervention (3 months)

• Change in Oxygen Uptake Kinetics (VO2 Kinetics)

  Oxygen uptake kinetics will be tested on a stationary bike before and after 3 months of study medication. VO2 kinetics is reported as the time constant associated with the change in oxygen update from rest to steady state.

  Pre-intervention (Baseline) and post-intervention (3 months)

• Changes From Baseline in 31P Measurement: Free Pi Time Constant

  Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment. Data are represented as the change in Pi through the scan.

  Pre-intervention (Baseline) and post-intervention (3 months)

• Changes From Baseline in 31P Measurement: Adenosine Triphosphate (ATP) Peaks

  Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment

  Pre-intervention (Baseline) and post-intervention (3 months)

• Changes From Baseline in 31P Measurement: Adenosine Diphosphate (ADP) Time Constant

  Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment

  Pre-intervention (Baseline) and post-intervention (3 months)

• Changes From Baseline in 31P Measurement: pH

  Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment

  Pre-intervention (Baseline) and post-intervention (3 months)

Secondary Outcomes (2)

• Changes From Baseline in Echocardiographic Measures (Stroke Volume)

  Pre-intervention (Baseline) and post-intervention (3 months)

• Change in (Non-invasively Measured) Deoxygenated Hemoglobin Concentration in the Vastus Lateralis During Exercise

  Pre-intervention (Baseline) and post-intervention (3 months)

Study Arms (2)

Sitagliptin plus placebo

EXPERIMENTAL

100 mg sitagliptin plus 2 mg placebo once daily for three months

Drug: Sitagliptin; Drug: Placebo

Glimepiride plus placebo

ACTIVE COMPARATOR

2 mg glimepiride plus 100 mg placebo once daily for three months

Drug: Glimepiride; Drug: Placebo

Interventions

Sitagliptin DRUG

100 mg sitagliptin

Also known as: Januvia (sitagliptin)

Sitagliptin plus placebo

Glimepiride DRUG

Active Comparator 2mg glimepiride

Also known as: Amaryl

Glimepiride plus placebo

Placebo DRUG

2 mg placebo once daily

Also known as: Placebo 1-sitagliptin

Sitagliptin plus placebo

Eligibility Criteria

• Age: 22 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subjects may be pre, peri or post-menopausal.
• People who do not participate in a regular exercise program (\> one bout of exercise per week).
• 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.
• 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.
• 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.
• Persons not taking medication to control diabetes.

You may not qualify if:

• Females of childbearing potential who are pregnant, planning to become pregnant or breastfeeding.
• 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.
• Persons with angina or any other cardiac or pulmonary symptoms potentially limiting exercise performance.
• Presence of systolic blood pressure \>190 at rest or \>250 with exercise or diastolic pressure \>95 at rest or \>115 with exercise.
• Subjects who have peripheral arterial disease.
• Subjects with proteinuria (urine protein \>200 mg/dl) or a creatinine \> 2 mg/dl, suggestive of renal disease.
• Persons with liver function impairment defined as elevated liver function tests three times the upper limit.
• Persons with a history of pancreatitis.
• Subjects more than 140% of ideal body weight.
• Patients on insulin therapy will not be included.
• 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.
• Persons with autonomic dysfunction (\>20 mm fall in upright blood pressure without a change in heart rate) will be excluded.
• 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).
• Persons with diabetic ketoacidosis.
• Persons with a serious hypersensitivity to sitagliptin, sulfonylureas or sulfonamides.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Scalzo RL, Rafferty D, Schauer I, Huebschmann AG, Cree-Green M, Reusch JEB, Regensteiner JG. Sitagliptin improves diastolic cardiac function but not cardiorespiratory fitness in adults with type 2 diabetes. J Diabetes Complications. 2019 Aug;33(8):561-566. doi: 10.1016/j.jdiacomp.2019.05.002. Epub 2019 May 10.

  PMID: 31182338 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases; Diabetes Mellitus; Motor Activity

Interventions

Sitagliptin Phosphate; glimepiride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Judy Regensteiner
• Organization: University of Colorado

judy.regensteiner@ucdenver.edu

303-724-2247

Study Officials

• Judith G. Regensteiner, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Jane EB Reusch, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: September 26, 2013
• Study Start: October 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: July 12, 2023
• Results First Posted: May 22, 2019

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)