Clinical trial NCT02951260: The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation
Official title: The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2016-11-01
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall aerobic work performed during an exercise bout with self-selected intensity
timeFrame: Total oxygen consumption (L O2) during a 45 min ergometer cycling bout with self-selected intensity
Secondary outcomes:
measure: External work performed during an exercise bout with self-selected intensity
timeFrame: Total work produced (kJ) during a 45 min ergometer cycling bout with self-selected intensity
measure: Rate of perceived exertion during an exercise bout with fixed intensity
timeFrame: Mean rate of perceived exertion (Borg scale) during a 45 min ergometer cycling bout with fixed intensity
measure: blood lactate during an exercise bout with fixed intensity
timeFrame: Mean blood lactate (mmol/l) during a 45 min ergometer cycling bout with fixed intensity
measure: Heartrate during an exercise bout with fixed intensity
timeFrame: Mean heart rate (bpm) during a 45 min ergometer cycling bout with fixed intensity
measure: Respiratory exchange ratio during an exercise bout with fixed intensity
timeFrame: Mean VCO2/VO2 during a 45 min ergometer cycling bout with fixed intensity
measure: Physical fitness (VO2max)
timeFrame: maximal oxygen consumption (L/min) during a VO2 max test
Other outcomes:
measure: AMPK-activation in skeletal muscle during an exercise bout with fixed intensity
timeFrame: change in exercise induced AMPK-activation after compared to before a 45 min ergometer cycling bout with self-selected intensity
measure: Oxidative phosphorylation in skeletal muscle fibers
timeFrame: Mitochondrial Complex I respiration in skeletal muscle tissue after 17 days of metformin/placebo treatment
Locations:
city: Copenhagen
country: Denmark
facility: Center for aktiv sundhed
state: Copenhagen N
Study officials:
affiliation: Center for aktiv sundhed, Rigshospitalet
name: Kristian Karstoft, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pilmark NS, Oberholzer L, Halling JF, Kristensen JM, Bonding CP, Elkjaer I, Lyngbaek M, Elster G, Siebenmann C, Holm NFR, Birk JB, Larsen EL, Lundby AM, Wojtaszewski J, Pilegaard H, Poulsen HE, Pedersen BK, Hansen KB, Karstoft K. Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of 2 randomized, clinical trials. Appl Physiol Nutr Metab. 2022 Mar;47(3):309-320. doi: 10.1139/apnm-2021-0194. Epub 2021 Nov 16.