Metformin and Vascular Function in Prediabetes

December 17, 2025 updated by: Diana Jalal

The goal of this clinical trial is to investigate whether metformin improves vascular function in individuals with prediabetes. The main questions it aims to answer are:

  1. Does metformin improve large conduit artery endothelial function in individuals with prediabetes?
  2. Does metformin improve microvascular endothelial function in individuals with prediabetes?

Researchers will compare metformin to a placebo to see if metformin improves vascular function in prediabetes.

The trial duration is 12 weeks. Participants will take metformin or a placebo once a day for 2 weeks. After 2 weeks, participants will take metformin or a placebo twice a day for the remaining 10 weeks. There will be a screening visit, two baseline visits, a 4-week safety visit, and two 12-week end-of-study visits. Adherence will be calculated from pill count and adverse events will be quantified via a questionnaire.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Prediabetes affects approximately 98 million people in the United States and significantly elevates the risk of cardiovascular disease (CVD) and progression to type-2 diabetes. Endothelial dysfunction, characterized by reduced nitric oxide bioavailability, is a key subclinical risk factor contributing to the increased CVD risk in prediabetes. Additionally, endothelial dysfunction exacerbates insulin resistance and hyperglycemia, further elevating the likelihood of progression to overt diabetes. Thus, targeting endothelial dysfunction in prediabetes presents a strategic opportunity to mitigate the risks of both CVD and overt diabetes.

Hyperglycemia-induced reactive oxygen species (ROS) generation reduces nitric oxide bioavailability, driving endothelial dysfunction in prediabetes. Therefore, interventions that lower hyperglycemia could decrease ROS production, enhance nitric oxide bioavailability, and improve endothelial function in prediabetes. Metformin, a first-line anti-diabetic agent, lowers hyperglycemia by reducing hepatic glucose output and enhancing insulin-mediated glucose uptake. Despite its established vascular benefits in diabetes, the effects of metformin on endothelial function in prediabetes remain unexplored.

This study will enroll 30 individuals in a randomized, double-blind, placebo-controlled clinical trial utilizing innovative methodologies to elucidate the vascular benefits of metformin in prediabetes. Specifically, the investigators will assess 1) large conduit artery endothelial function, and 2) cutaneous microvascular endothelial function in prediabetes. By investigating these mechanisms, the investigators aim to provide critical insights into metformin's potential to reduce CVD risk and prevent the progression to diabetes in individuals with prediabetes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
      • Iowa City, Iowa, United States, 52245
        • University of Iowa Hospitals and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-55 years
  • Prediabetes defined as an HbA1c between 5.7% and 6.4%
  • Able to provide informed consent

Exclusion Criteria:

  • Current use of metformin or metformin use within the past 12 months
  • Current use of medicated contraindicated for use with metformin
  • Current use of vitamin C supplement
  • Current smoker or quit smoking within the last 6 months
  • Pregnant, breastfeeding, planning to become pregnant, or unwilling to use adequate birth control
  • Uncontrolled hypertension (Systolic blood pressure >140 mmHg)
  • Body Mass Index > 40 kg/m2
  • History of diabetes, myocardial infarction, heart failure, liver disease, or chronic kidney disease (estimated glomerular filtration rate < 45 ml/min/1.73m2)
  • History of lactic acidosis
  • History of alcohol abuse
  • Severe infection within the last 30 days
  • Immunosuppressive therapy within the past year
  • Life expectancy < 1 year
  • Allergy to metformin, nitroglycerin, sodium nitroprusside, ringer's lactate
  • Study compliance: Unwilling to fast overnight, have an intravenous catheter placed, take a study drug for 12 weeks, or visit Iowa campus 6 times within a 12-16 week period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Patients will receive placebo pill identical in appearance and taste to the supplement
Other: Placebo
Oral placebo for 12 weeks
Experimental: Metformin
Participants will receive metformin 850 mg PO once a day for 2 weeks. After 2 weeks, participants will receive metformin 1700 mg PO once a day for the remaining 10 weeks.
Drug: Metformin
Oral ingestion for 12 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Macrovascular endothelial function
Time Frame: 12 weeks
Brachial artery flow-mediated dilation
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Microvascular endothelial function
Time Frame: 12 weeks
Cutaneous microvascular dilation
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Diana Jalal

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Diana I Jalal, MD, University of Iowa

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 13, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 24, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 24, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202403617

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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