Clinical trial NCT03329651: The Interaction Between Metformin and Acute Exercise
Official title: The Interaction Between Metformin and Acute Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Impaired Glucose Tolerance
Diabetes Mellitus, Type 2
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2017-11-06
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Difference in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test
timeFrame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)
Secondary outcomes:
measure: Difference in endogenous glucose production as assessed by rate of infused glucose tracer appearance in blood
timeFrame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)
measure: Difference in exogenous glucose uptake as assessed by rate of ingested glucose tracer appearance in blood
timeFrame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)
measure: Difference in peripheral glucose uptake as assessed by rate of glucose disappearance from blood
timeFrame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Center for aktiv sundhed
state: Copenhagen N
Study officials:
affiliation: Rigshospitalet, Denmark
name: Kristian Karstoft, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: