Short-Term Metformin Use in Young, Healthy Adults: Impacts on Exercise Capacity

NCT06638671 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: HSR240014
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Metformin is the most prescribed blood sugar (glucose)-lowering medication for patients diagnosed with type 2 diabetes mellitus (T2DM). Metformin stimulates glucose uptake in skeletal muscle similar to the effects of exercise, though, some studies report that metformin may decrease exercise capacity. The main question this study looks to answer is:

• Does metformin alter exercise capacity? Participants will:
• Complete 5 exercise tests on a stationary bike.
• Undergo a body composition test.
• Take metformin and placebo.
• Complete food and symptom logs. The researchers hypothesize that:
• Metformin will reduce aerobic capacity.

Conditions

Metformin; Exercise Capacity

Keywords

Exercise capacity; Metformin; Lactate threshold

Outcome Measures

Primary Outcomes (5)

• Exercise capacity

  Exercise capacity will be measured by absolute and relative VO2peak

  6 weeks

• Lactate threshold

  Lactate threshold (LT) will be determined by power output immediately before the curvilinear increase in lactate concentration

  6 weeks

• VO2 at Lactate threshold

  VO2 at LT denoted as VO2 obtained at the same power output as LT

  6 weeks

• Lactate turnpoint (LTP)

  LTP will be determined by the power output obtained immediately before the second sharp increase in blood lactate concentration

  6 weeks

• Maximal power output

  Maximal power output (watts) during exercise

  6 weeks

Secondary Outcomes (3)

• Respiratory exchange ratio (RER)

  6 weeks

• Ventilation (VE)

  6 weeks

• Maximal fat oxidation (Fatmax)

  6 weeks

Other Outcomes (5)

• Resting blood pressure

  6 weeks

• Blood pressure during exercise

  6 weeks

• Resting heart rate

  6 weeks

Study Arms (2)

Metformin (MET)

EXPERIMENTAL

At the end of the screening visit, participants will be randomized to either Condition A or Condition B (MET or PL first). Participants will begin the 19-day treatment phase of study the day after screening. During each treatment phase, participants will consume metformin as follows: 1x500 mg tablet/day for 5 days, 2x500 mg tablets/day for 5 days, and 3x500 mg tablets/day (or maximally tolerated dosage) for 9 days. Participants will then complete a VO2peak/LT test on day 16, rest for 48 hours, then complete a time-to-exhaustion test (day 19) during the final days of the treatment phase. After the time-to-exhaustion test, participants will begin the placebo treatment phase.

Drug: Metformin Hydrochloride

Placebo (PL)

PLACEBO COMPARATOR

At the end of the screening visit, participants will be randomized to either Condition A or Condition B (MET or PL first). Participants will begin the 19-day treatment phase of study the day after screening. During each treatment phase, participants will consume placebo as follows: 1x500 mg tablet/day for 5 days, 2x500 mg tablets/day for 5 days, and 3x500 mg tablets/day (or maximally tolerated dosage) for 9 days. Participants will then complete a VO2peak/LT test on day 16, rest for 48 hours, then complete a time-to-exhaustion test (day 19) during the final days of the treatment phase. After the time-to-exhaustion test, participants will begin the metformin treatment phase.

Drug: Placebo

Interventions

Placebo DRUG

Participants will consume metformin or placebo in a randomized order. Participants will complete exercise visits during each treatment phase.

Placebo (PL)

Metformin Hydrochloride DRUG

Participants will consume metformin or placebo in a randomized order. Participants will complete exercise visits during each treatment phase.

Metformin (MET)

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years old
• Metformin-naïve
• BMI \< 30 kg/m2
• Recreationally active (≥ 3 days/week of exercise)
• Females must be premenopausal and report normal menstrual cycles
• Willingness and ability to comply with scheduled visits and study procedures.

You may not qualify if:

• History of cardiometabolic disease, such as type 1 or type 2 diabetes
• Smoking (must have quit at least 6 mos prior)
• Use of medication that significantly alters glucose regulation (e.g., metformin, insulin, GLP-1 receptor agonists, SGLT-2 inhibitors, biguanides)
• Severe liver or kidney disease, or medications to treat liver or kidney disease
• Pregnant, breastfeeding, or plans to become pregnant during study period

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Jason D Allen, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomized, double-blind, placebo-controlled crossover design

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: October 15, 2024
• Study Start: January 31, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)