The Interaction Between Metformin and Physical Training

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Interaction Between Metformin and Physical Training

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03316690
• Other study ID #: H-17012307
• Status: Completed
• Phase: N/A
• Start date: October 20, 2017
• Est. completion date: October 1, 2018

Study information

• Verified date: November 2018
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: October 1, 2018
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Impaired Glucose Tolerance

Intervention

Drug:
• Metformin treatment
Daily treatment with metformin tablets for 101 days according to the following scheme: Day 1-4: Metformin tablet 500 mg x 2 Day 5-8: Metformin tablet 1000 + 500 mg Day 9-101: Metformin tablet 1000 mg x 2
• Placebo treatment
Daily treatment with placebo tablets for 101 days according to the following scheme: Day 1-4: Placebo tablet 500 mg x 2 Day 5-8: Placebo tablet 1000 + 500 mg Day 9-101: Placebo tablet 1000 mg x 2

Behavioral:
• Physical training
Twelve weeks of supervised physical training (4 times per week, 45 min per session, mean intensity at 70% of maximal oxygen consumption rate)

Locations

Country	Name	City	State
Denmark	Center for aktiv sundhed	Copenhagen	Copenhagen N

Sponsors (2)

Lead Sponsor	Collaborator
Kristian Karstoft	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test		Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in free-living glycemic control	Blood HbA1c levels	Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Change in maximal oxygen consumption	Maximal oxygen uptake during an incremental bicycle test	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in body weight	Body weight measured by standard procedures	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in lean body mass	Lean body mass evaluated via Dual energy x-ray absorptiometry (Dxa)	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in total fat mass	Total body fat mass evaluated via Dual energy x-ray absorptiometry (Dxa)	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in visceral fat mass	Visceral fat mass evaluated via magnetic resonance imaging (MRI) scans	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in AMPK activity in skeletal muscle	AMPK activity measured via western blotting and activity assays	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in skeletal muscle oxidative stress	Muscle mitochondrial oxidative stress measured via respirometry in muscle biopsies	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Change in systemic oxidative stress	Systemic oxidative stress measured via RNA/DNA oxidation products in urine	Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Maximal mitochondrial respiration	Maximal mitochondrial respiration measured via respirometry in muscle biopsies	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Secondary	Training heart rate	Heart rate will be measured continuously during all training sessions	Average heart rate during all training sessions (through study completion, [Day 101])
Secondary	Training rate of perceived exertion	Rate of perceived exertion measured via a Borg scale (range 6-20 where higher values indicate higher rate of perceived exertion) will be assessed for each training session	Average rate of perceived exertion of all training sessions (through study completion, [Day 101])