The Interaction Between Metformin and Physical Training

NCT03316690 | Completed DMC

• 1 other identifier: H-17012307
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Impaired Glucose Tolerance; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Change in free-living glycemic control

  Day 0 (before randomisation), 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 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 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)

• Change in maximal oxygen consumption

  Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)

Study Arms (2)

Metformin treatment

EXPERIMENTAL

Drug: Metformin treatment; Behavioral: Physical training

Placebo treatment

PLACEBO COMPARATOR

Drug: Placebo treatment; Behavioral: Physical training

Interventions

Metformin treatment DRUG

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

Metformin treatment

Placebo treatment DRUG

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

Placebo treatment

Physical training BEHAVIORAL

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

Metformin treatment; Placebo treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kristian Karstoft: lead
• University of Copenhagen: collaborator

Study Sites (1)

Center for aktiv sundhed

Copenhagen, Copenhagen N, 2200, Denmark

Location

Related Publications (2)

• 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.

  PMID: 34784247 DERIVED

• Pilmark NS, Lyngbaek M, Oberholzer L, Elkjaer I, Petersen-Bonding C, Kofoed K, Siebenmann C, Kellenberger K, van Hall G, Abildgaard J, Ellingsgaard H, Lauridsen C, Ried-Larsen M, Pedersen BK, Hansen KB, Karstoft K. The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomised, clinical trial. Diabetologia. 2021 Feb;64(2):397-409. doi: 10.1007/s00125-020-05282-6. Epub 2020 Sep 26.

  PMID: 32979074 DERIVED

MeSH Terms

Conditions

Glucose Intolerance; Diabetes Mellitus, Type 2

Interventions

Physical Conditioning, Human

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Kristian Karstoft, MD, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 20, 2017
• Study Start: October 20, 2017
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: November 9, 2018

Record last verified: 2018-11

Locations

DK (1)