The Interaction Between Metformin and Physical Training
Overview
- Phase
- Not Applicable
- Intervention
- Metformin treatment
- Conditions
- Impaired Glucose Tolerance
- Sponsor
- Kristian Karstoft
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Change in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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 training with and without concomitant metformin treatment, in order to investigate whether an interaction between the two occur.
Subjects with impaired glucose tolerance will all undergo 12 weeks of training but will be randomized (1:1) to concomitant metformin/placebo treatment in a double-blinded way. Experimental days will be performed before randomisation (before initiation of metformin/placebo treatment), before initiation of the training period and after the training period.
Investigators
Kristian Karstoft
Principal Investigator
Rigshospitalet, Denmark
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
- •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 reduce 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
Arms & Interventions
Metformin treatment
Intervention: Metformin treatment
Metformin treatment
Intervention: Physical training
Placebo treatment
Intervention: Placebo treatment
Placebo treatment
Intervention: Physical training
Outcomes
Primary Outcomes
Change in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test
Time Frame: Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary Outcomes
- Change in systemic oxidative stress(Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in lean body mass(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Maximal mitochondrial respiration(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in endogenous glucose production as assessed by rate of infused glucose tracer appearance in blood(Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in peripheral glucose uptake as assessed by rate of glucose disappearance from blood(Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Training heart rate(Average heart rate during all training sessions (through study completion, [Day 101]))
- Training rate of perceived exertion(Average rate of perceived exertion of all training sessions (through study completion, [Day 101]))
- Change in exogenous glucose uptake as assessed by rate of ingested glucose tracer appearance in blood(Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in maximal oxygen consumption(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in body weight(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in total fat mass(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in visceral fat mass(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in AMPK activity in skeletal muscle(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in skeletal muscle oxidative stress(Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))
- Change in free-living glycemic control(Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training))