Impaired Glucose ToleranceNCT03316690
The Interaction Between Metformin and Physical Training
A study testing Metformin treatment and Physical training in people with Impaired Glucose Tolerance and Diabetes Mellitus, Type 2, run by Kristian Karstoft at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Impaired Glucose Tolerance, Diabetes Mellitus, Type 2
- What is being tested?
- Metformin treatment and Physical training
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Oct 2017to 1 Oct 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Being tested
- Metformin treatment, Placebo treatment, Physical training
- Medical subject headings
- Glucose Intolerance, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin treatmentDrug
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 treatmentDrug
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
Physical trainingBehavioural
Twelve weeks of supervised physical training (4 times per week, 45 min per session, mean intensity at 70% of maximal oxygen consumption rate)
| Study group | Role | What they receive |
|---|---|---|
| Metformin treatment | Experimental | Not described Receives: Drug: Metformin treatment; Behavioral: Physical training |
| Placebo treatment | Placebo comparator | Not described Receives: Drug: Placebo treatment; Behavioral: Physical training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test
Measured: 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
Blood HbA1c levels
Measured: 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
Measured: 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
Measured: 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
Measured: Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in maximal oxygen consumption
Maximal oxygen uptake during an incremental bicycle test
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in body weight
Body weight measured by standard procedures
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in lean body mass
Lean body mass evaluated via Dual energy x-ray absorptiometry (Dxa)
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in total fat mass
Total body fat mass evaluated via Dual energy x-ray absorptiometry (Dxa)
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in visceral fat mass
Visceral fat mass evaluated via magnetic resonance imaging (MRI) scans
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in AMPK activity in skeletal muscle
AMPK activity measured via western blotting and activity assays
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in skeletal muscle oxidative stress
Muscle mitochondrial oxidative stress measured via respirometry in muscle biopsies
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in systemic oxidative stress
Systemic oxidative stress measured via RNA/DNA oxidation products in urine
Measured: Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Maximal mitochondrial respiration
Maximal mitochondrial respiration measured via respirometry in muscle biopsies
Measured: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Training heart rate
Heart rate will be measured continuously during all training sessions
Measured: Average heart rate during all training sessions (through study completion, [Day 101])
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
Measured: Average rate of perceived exertion of all training sessions (through study completion, [Day 101])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2017
- Study start20 Oct 2017
- Primary completion1 Oct 2018
- Study completion1 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Impaired Glucose ToleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kristian Karstoft
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Sponsor-investigator, Kristian Karstoft, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Kristian Karstoft, MD, PhD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03316690
- Sponsor's protocol ID
- H-17012307
- Status last verified
- Nov 2018
- First submitted
- 3 Oct 2017
- Last updated
- 9 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34784247Pilmark 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.
PubMed 32979074
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Interaction Between Metformin and Physical Training
- ClinicalTrials.gov ID
- NCT03316690
- Acronym / sponsor ID
- H-17012307
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Kristian KarstoftUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- 20 Oct 2017 (actual)
- Primary completion
- 1 Oct 2018 (actual)
- Study completion
- 1 Oct 2018 (actual)
- First posted
- 20 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin treatment | Experimental | Drug: Metformin treatment, Behavioral: Physical training |
| Placebo treatment | Placebo comparator | Drug: Placebo treatment, Behavioral: Physical training |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (9 listed)
- Pregnancy
- Smoking
- Glucose-lowering treatment
- Treatment with steroids and other immunomodulating drugs
- Contraindication to increased levels of physical activity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin treatmentDaily 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 | Drug | Metformin treatment |
| Placebo treatmentDaily 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 | Drug | Placebo treatment |
| Physical trainingTwelve weeks of supervised physical training (4 times per week, 45 min per session, mean intensity at 70% of maximal oxygen consumption rate) | Behavioural | Metformin treatment, Placebo treatment |
Primary outcome
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)
15 secondary outcomes
Change in free-living glycemic control
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in maximal oxygen consumption
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in body weight
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in lean body mass
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in total fat mass
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in visceral fat mass
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in AMPK activity in skeletal muscle
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in skeletal muscle oxidative stress
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Change in systemic oxidative stress
Time frame: Day 0 (before randomisation), 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Maximal mitochondrial respiration
Time frame: Day 17 (after initiation of metformin/placebo treatment), 101 (after 12 weeks of training)
Training heart rate
Time frame: Average heart rate during all training sessions (through study completion, [Day 101])
Training rate of perceived exertion
Time frame: Average rate of perceived exertion of all training sessions (through study completion, [Day 101])
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2018.
- Derived from this study: PubMed 34784247Pilmark 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.
- Derived from this study: PubMed 32979074Pilmark 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristian Karstoft, MD, PhD principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metformin treatment and Physical training in people with Impaired Glucose Tolerance and Diabetes Mellitus, Type 2, run by Kristian Karstoft at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03316690, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2018; AzTrials last refreshed its copy on 29 Oct 2026.