The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the potential interaction between metformin and exercise in order to optimize clinical guidelines for treatment of T2D.

Detailed Description
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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 AMPK, which results in many different metabolic effects. Because of this similarity, an interaction between metformin and exercise is plausible, but knowledge in the area is sparse. With this study the investigators aim to look at the individual and combined effects of metformin and exercise in order to investigate whether an interaction occur. An Interaction will have tremendous clinical importance for patients with T2D given current guidelines where the vast majority of these patients are recommended both exercise and metformin treatment. The investigators hypothesize that metformin treatment reduces self-selected exercise intensity, which may be explained via decreased mitochondrial complex 1 function, increased blood lactate levels, heart rate and RPE during exercise. Furthermore exercise-induced AMPK-activation is reduced with metformin treatment.

Official Title
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The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Metformin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male HbA1c < 39 mmol/l BMI < 25 structured physical activity < = 150 min/week apparently healthy Exclusion Criteria: smoking daily pharmaceutical treatment contraindication to increased levels of physical activity ALAT/ASAT elevated 3 times above upper normal values renal insufficiency (eGFR < 60 ml/min) prior history of lactic acidosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>17 days metformin treatment | Drug: Metformin<br>* 17 days treatment with metformin<br>|
| Placebo Comparator: Placebo<br>17 days placebo treatment | Other: Placebo<br>* 17 days treatment with placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall aerobic work performed during an exercise bout with self-selected intensity |  | Total oxygen consumption (L O2) during a 45 min ergometer cycling bout with self-selected intensity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| External work performed during an exercise bout with self-selected intensity |  | Total work produced (kJ) during a 45 min ergometer cycling bout with self-selected intensity | 
| Rate of perceived exertion during an exercise bout with fixed intensity |  | Mean rate of perceived exertion (Borg scale) during a 45 min ergometer cycling bout with fixed intensity | 
| blood lactate during an exercise bout with fixed intensity |  | Mean blood lactate (mmol/l) during a 45 min ergometer cycling bout with fixed intensity | 
| Heartrate during an exercise bout with fixed intensity |  | Mean heart rate (bpm) during a 45 min ergometer cycling bout with fixed intensity | 
| Respiratory exchange ratio during an exercise bout with fixed intensity |  | Mean VCO2/VO2 during a 45 min ergometer cycling bout with fixed intensity | 
| Physical fitness (VO2max) |  | maximal oxygen consumption (L/min) during a VO2 max test |