The Interaction Between Metformin and Physical Training

Not Applicable

Completed

• Conditions: Impaired Glucose Tolerance; Diabetes Mellitus, Type 2
• Interventions: Drug: Metformin treatment; Drug: Placebo treatment; Behavioral: Physical training

• Registration Number: NCT03316690
• Lead Sponsor: Kristian Karstoft

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-03
• Study First Submitted QC: 2017-10-17
• Study Start: 2017-10-20
• Study First Posted: 2017-10-20
• Primary Completion: 2018-10-01
• Study Completion: 2018-10-01
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-07
• Last Update Posted: 2018-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin treatment	Metformin treatment	-
Metformin treatment	Physical training	-
Placebo treatment	Placebo treatment	-
Placebo treatment	Physical training	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Change in systemic oxidative stress	Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Systemic oxidative stress measured via RNA/DNA oxidation products in urine
Change in lean body mass	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Lean body mass evaluated via Dual energy x-ray absorptiometry (Dxa)
Maximal mitochondrial respiration	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Maximal mitochondrial respiration measured via respirometry in muscle biopsies
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])	Heart rate will be measured continuously during all training sessions
Training rate of perceived exertion	Average rate of perceived exertion of all training sessions (through study completion, [Day 101])	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
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)	Maximal oxygen uptake during an incremental bicycle test
Change in body weight	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Body weight measured by standard procedures
Change in total fat mass	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Total body fat mass evaluated via Dual energy x-ray absorptiometry (Dxa)
Change in visceral fat mass	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Visceral fat mass evaluated via magnetic resonance imaging (MRI) scans
Change in AMPK activity in skeletal muscle	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	AMPK activity measured via western blotting and activity assays
Change in skeletal muscle oxidative stress	Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Muscle mitochondrial oxidative stress measured via respirometry in muscle biopsies
Change in free-living glycemic control	Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)	Blood HbA1c levels

Trial Locations

Locations (1)

Center for aktiv sundhed; 🇩🇰 Copenhagen, Copenhagen N, Denmark