Phase 3
N=91
Exercise Dose and Metformin for Vascular Health in Metabolic Syndrome
Metabolic Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT03355469 ↗Enrolled (actual)
91
Serious AEs
0.0%
Results posted
Sep 2025
Primary outcome: Primary: Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery — -0.45; 0.76; 3.50; 5.28 Percent change in diameters — p=0.045
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Metformin (Drug); Placebo (Drug); Low Intensity Exercise (Behavioral); High Intensity Exercise (Behavioral)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Rutgers University
- Primary completion
- Mar 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery |
-0.45; 0.76; 3.50; 5.28 | 0.045 sig |
| SECONDARY Change in Metabolic Insulin Sensitivity. Glucose Infusion Rate Normalized to Steady-State Insulin (GIR). |
0.0012; 0.011; 0.0086; 0.0053 | 0.373 |
| SECONDARY Change in Fasting Augmentation Index |
-1.33; -4.65; 0.00; -1.20 | 0.671 |
| SECONDARY Change in Insulin-stimulated Microvascular Blood Flow (MBF) of the Forearm. |
0.027; 0.041; -0.026; -0.065 | 0.088 |
| SECONDARY Change in Insulin-stimulated Microvascular Flow Velocity (MFV) of the Forearm. |
0.006; 0.009; -0.007; -0.018 | 0.147 |
| SECONDARY Change in Insulin-stimulated Microvascular Blood Volume (MBV) of the Forearm. |
0.188; 0.433; -0.257; -0.510 | 0.086 |
Summary
Health organizations recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease. Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and cardiovascular disease (CVD) risk. However, the optimal dose of exercise to be combined with metformin for vascular health remains unknown. The purpose of this study is to evaluate whether combining high or low intensity exercise with metformin has the potential to outperform either exercise intensity alone on blood flow across the arterial tree as well as impact insulin action in individuals with metabolic syndrome. Identification of such outcomes will indicate 1) whether and how metformin should be combined with physical activity for CVD prevention, 2) provide the first indication of whether exercise intensity reduces CVD risk via multi-level vasculature function vs. metabolic insulin action, and 3) provide a rational early treatment for people with metabolic syndrome to prevent/treat type 2 diabetes and CVD.
Eligibility Criteria
Inclusion Criteria
- Male or female ≥40 and ≤80 years old.
- Has a body mass index ≥25 and ≤47 kg/m2.
- Not diagnosed with Type 2 or Type 1 diabetes
- Not currently engaged in > 150 min/wk of exercise
- Weight stable ( 5 years
At minimum, subject will have abdominal obesity (increased waist circumference as defined below) and may have any additional National Cholesterol Education Adult Treatment Panel III Metabolic Syndrome criteria:
- Increased waist circumference (≥102 cm in men; ≥88 cm in women)
- Elevated triglycerides (≥150 mg/dl), or on medication for treating the condition
- Reduced HDL-cholesterol ( 130 mg/dL
- Family history of type 2 diabetes (immediate family, i.e. parent/sibling)
- History of gestational diabetes
- History of Polycystic Ovarian Syndrome
- Family history of pre-mature cardiovascular disease (immediate family i.e. parent/sibling) before 55 for males or 65 for females that can include heart attack, peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease or clinical coronary heart disease)
- Age ( > 45 years old for men; > 55 years old for women)
- Black/African American, Mexican, Asian, and/or Hispanic
- Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers)
Exclusion Criteria
- Subjects prescribed metformin or have taken metformin within 1 year.
- Subjects with abnormal estimated glomerular filtration rate (eGFR).
- Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
- Hypertensive (>160/100 mmHg)
- Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
- Pregnant (as evidenced by positive pregnancy test) or nursing women
- Subjects with contraindications to participation in an exercise training program
- Currently taking active weight suppression medication (e.g. phentermine,orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
- Known hypersensitivity to perflutren (contained in Definity)
- Subjects who are considered non-English speaking individuals
Data sourced from ClinicalTrials.gov (NCT03355469). 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.