The Interaction Between Metformin and Acute Exercise

NCT03329651 | Completed DMC

• 1 other identifier: H-17012307-1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Impaired Glucose Tolerance; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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)

Study Arms (2)

Metformin treatment

EXPERIMENTAL

Drug: Metformin treatment

Placebo treatment

PLACEBO COMPARATOR

Drug: Placebo treatment

Interventions

Metformin treatment DRUG

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

Metformin treatment

Placebo treatment DRUG

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

Placebo treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kristian Karstoft: lead
• University of Copenhagen: collaborator

Study Sites (1)

Center for aktiv sundhed

Copenhagen, Copenhagen N, 2200, Denmark

Location

MeSH Terms

Conditions

Glucose Intolerance; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Kristian Karstoft, MD, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: November 10, 2017
• Primary Completion: July 1, 2018
• Study Completion: October 1, 2018
• Last Updated: November 9, 2018

Record last verified: 2018-11

Locations

DK (1)