The Interaction Between Metformin and Acute Exercise

Physical activity is a first line treatment for patients with type 2 diabetes (T2D), however, the vast majority of patients with T2D do not achieve satisfying glycemic control with physical activity alone, which is why pharmacological treatment with metformin is most often initiated.

It is known that metformin and exercise both activates 5' adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle and liver, and the activation of AMPK results in many different metabolic effects, including improvements in glycemic control. Because of this similarity in mechanism of action, an interaction between metformin and exercise is plausible, but knowledge in the area is sparse. Thus, the aim of this study is to assess the effects of acute physical activity with and without concomitant metformin treatment, in order to investigate whether an interaction between the two occur.

Subjects with impaired glucose tolerance will be randomized (1:1) to metformin/placebo treatment in a double-blinded way. Following a treatment run-in period of 17 days, two experimental days (one with acute exercise and one without acute exercise), separated by one week, will be performed in each subject.

This registration concerns a sub-study of another study which has previously been registrered at ClinicalTrials.gov (Unique Protocol ID: H-17012307). The specific outcomes in this registration have not previously been registered.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: Metformin treatment; Drug: Placebo treatment

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen N
    • Copenhagen, Copenhagen N, Denmark, 2200
      • Center for aktiv sundhed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Glucose-lowering-medication naïve T2D and/or subjects with impaired glucose tolerance defined as: 2-h plasma glucose (PG) in the 75-g OGTT (7.8-11.0 mmol/L) and/or HbA1c (39-47 mmol/mol)
• Caucasian
• BMI > 25 but < 40 kg/m2
• Low to moderate physically active (≤90 min of structured physical activity/week)

Exclusion Criteria:

• Pregnancy
• Smoking
• Glucose-lowering treatment
• Treatment with steroids and other immunomodulating drugs
• Contraindication to increased levels of physical activity
• Liver disease (ALAT elevated more than 3 times above upper normal limit, or reduced levels of the liver function markers albumin and KF II+VII+X)
• Renal insufficiency (eGFR<60 ml/min)
• Prior history of lactic acidosis
• HbA1c >55 mmol/mol and/or 2-hPG in the 75-g OGTT > 15 mmol/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo treatment	Drug: Placebo treatment; Daily treatment with placebo tablets for 24 days according to the following scheme: Day 1-4: Placebo tablet 500 mg x 2 Day 5-8: Placebo tablet 1000 + 500 mg Day 9-24: Placebo tablet 1000 mg x 2
Experimental: Metformin treatment	Drug: Metformin treatment; Daily treatment with metformin tablets for 24 days according to the following scheme: Day 1-4: Metformin tablet 500 mg x 2 Day 5-8: Metformin tablet 1000 + 500 mg Day 9-24: Metformin tablet 1000 mg x 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test	Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference in endogenous glucose production as assessed by rate of infused glucose tracer appearance in blood	Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)
Difference in exogenous glucose uptake as assessed by rate of ingested glucose tracer appearance in blood	Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)
Difference in peripheral glucose uptake as assessed by rate of glucose disappearance from blood	Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)

Collaborators and Investigators

• Sponsor: Kristian Karstoft
• Collaborators: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2017
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 9, 2018
• Last Update Submitted That Met QC Criteria: November 7, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Diabetes Mellitus, Type 2; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: H-17012307-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No