Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06638671
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-23
Brief Title:
Short-Term Metformin Use in Young Healthy Adults Impacts on Exercise Capacity
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Short-Term Metformin Use in Young Healthy Adults Impacts on the Blood Lactate Response to Exercise and Time-to-exhaustion in a Placebo-controlled Crossover Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Metformin is the most prescribed blood sugar glucose-lowering medication for patients diagnosed with type 2 diabetes mellitus T2DM Metformin stimulates glucose uptake in skeletal muscle similar to the effects of exercise though some studies report that metformin may decrease exercise capacity
The main question this study looks to answer is
Does metformin alter exercise capacity
Participants will
Complete 5 exercise tests on a stationary bike
Take metformin and placebo
Complete food and symptom logs
The researchers hypothesize that
Metformin will reduce aerobic capacity
The main question this study looks to answer is
Does metformin alter exercise capacity
Participants will
Complete 5 exercise tests on a stationary bike
Take metformin and placebo
Complete food and symptom logs
The researchers hypothesize that
Metformin will reduce aerobic capacity
Detailed Description:
Metformin a potent biguanide is the most prescribed glucose-lowering medication for patients newly diagnosed with type 2 diabetes mellitus T2DM Metformin has purported utility for various conditions such as aging autoimmune conditions and cancer however the primary use of metformin is for blood glucose reduction via decreased glucose production in the liver increased glycogenesis decreased glycogenolysis and gluconeogenesis reduced glucose absorption in the gut and enhanced insulin-independent skeletal muscle glucose uptake The effect of metformin within skeletal muscle is the focus of this study
The mechanism for improved metformin-mediated skeletal muscle glucose uptake involves the inhibition of complex 1 NADHubiquinone oxidoreductase in the mitochondrial electron transport chain ETC This leads to a reduced cellular energy charge marked by a reduced ATP concentration and increased ratios of ADPATP and AMPATP This energetic imbalance initiates phosphorylation of 5 adenosine monophosphate-activated protein kinase AMPK which in turn induces glucose transporter GLUT4 translocation to the cell membrane and upregulates insulin-independent glucose uptake by skeletal muscle fibers This cellular energy imbalance and subsequent AMPK signaling cascade is similar to stress elicited by exercise However during exercise the energy imbalance is created by increased ATP utilization from skeletal muscle contraction rather than incomplete glucose metabolism less ATP per glucose and an increased reliance on glycolysis
Exercise training is considered the gold standard approach to enhanced cardiorespiratory fitness and peripheral insulin sensitivity across the lifespan Metformin also benefits glycemic control and reduces cardiovascular risk Although the evidence is not conclusive metformin has been shown to potentially decrease exercise capacity in healthy subjects and those with metabolic syndrome Importantly due to the increased reliance on anaerobic metabolism metformin may reduce the lactate threshold LT and lactate turn point LTP which are strong predictors of perception of effort submaximal fitness and endurance performance Given cardiorespiratory fitness strength glucose control and insulin sensitivity are predictors of disease disability and all-cause mortality it is important to determine the effects of metformin on cardiorespiratory fitness and physical function
While these mechanisms of metformin in skeletal muscle are compelling for glucose regulation there is significant variation in the literature on the effects of metformin on exercise capacity largely due to differences in dosing eg 50-500 mgkg and exercise intervention design eg acute vs short-term or chronic exercise andor submaximal vs maximal exercise intensity A recent meta-analysis by found that because previous studies have predominantly used exercise intensities well below VO2max metformin does not appear to affect maximal oxygen uptake in healthy volunteers metformin may only alter exercise capacity at high or near-maximal work rates Thus there is a lack of data on the effects of metformin on lactate threshold blood lactate clearance and exercise-induced fatigue
Data from this study will provide valuable insight into the effects of metformin compared to placebo on exercise capacity at near-maximal work rates in young healthy adults While some studies have examined metformins impact on exercise performance these tend to be studies where exercise intensity was well below maximal effort in highly trained cyclists or in clinical populations eg individuals with T2DM Importantly the results from this study may lead healthy individuals to adjust exercise protocols to accommodate for the decline in performance along with an increased perceived exertion that may accompany metformin consumption Moreover this study may fill the gap in literature on a slightly longer timeline for metformin ingestion effects on exercise capacity compared to acute consumption which may have a more profound impact on cardiorespiratory fitness and capacity over time
The mechanism for improved metformin-mediated skeletal muscle glucose uptake involves the inhibition of complex 1 NADHubiquinone oxidoreductase in the mitochondrial electron transport chain ETC This leads to a reduced cellular energy charge marked by a reduced ATP concentration and increased ratios of ADPATP and AMPATP This energetic imbalance initiates phosphorylation of 5 adenosine monophosphate-activated protein kinase AMPK which in turn induces glucose transporter GLUT4 translocation to the cell membrane and upregulates insulin-independent glucose uptake by skeletal muscle fibers This cellular energy imbalance and subsequent AMPK signaling cascade is similar to stress elicited by exercise However during exercise the energy imbalance is created by increased ATP utilization from skeletal muscle contraction rather than incomplete glucose metabolism less ATP per glucose and an increased reliance on glycolysis
Exercise training is considered the gold standard approach to enhanced cardiorespiratory fitness and peripheral insulin sensitivity across the lifespan Metformin also benefits glycemic control and reduces cardiovascular risk Although the evidence is not conclusive metformin has been shown to potentially decrease exercise capacity in healthy subjects and those with metabolic syndrome Importantly due to the increased reliance on anaerobic metabolism metformin may reduce the lactate threshold LT and lactate turn point LTP which are strong predictors of perception of effort submaximal fitness and endurance performance Given cardiorespiratory fitness strength glucose control and insulin sensitivity are predictors of disease disability and all-cause mortality it is important to determine the effects of metformin on cardiorespiratory fitness and physical function
While these mechanisms of metformin in skeletal muscle are compelling for glucose regulation there is significant variation in the literature on the effects of metformin on exercise capacity largely due to differences in dosing eg 50-500 mgkg and exercise intervention design eg acute vs short-term or chronic exercise andor submaximal vs maximal exercise intensity A recent meta-analysis by found that because previous studies have predominantly used exercise intensities well below VO2max metformin does not appear to affect maximal oxygen uptake in healthy volunteers metformin may only alter exercise capacity at high or near-maximal work rates Thus there is a lack of data on the effects of metformin on lactate threshold blood lactate clearance and exercise-induced fatigue
Data from this study will provide valuable insight into the effects of metformin compared to placebo on exercise capacity at near-maximal work rates in young healthy adults While some studies have examined metformins impact on exercise performance these tend to be studies where exercise intensity was well below maximal effort in highly trained cyclists or in clinical populations eg individuals with T2DM Importantly the results from this study may lead healthy individuals to adjust exercise protocols to accommodate for the decline in performance along with an increased perceived exertion that may accompany metformin consumption Moreover this study may fill the gap in literature on a slightly longer timeline for metformin ingestion effects on exercise capacity compared to acute consumption which may have a more profound impact on cardiorespiratory fitness and capacity over time
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None