PreDiabetesPhase 4NCT03398356
Metformin and Its Impact on the Substances Associated With NO Production in Prediabetes Patients.
A Phase 4 study testing Metformin in people with PreDiabetes and Impaired Fasting Glucose (IFG), run by Wroclaw Medical University at 1 site in Poland.
Trial summary
This study evaluates the effect of different doses of metformin on the function of endothelium in people with pre-diabetes. One group of the patients will receive metformin in dose: 1500 mg, the second one will receive 3000 mg/day. Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- PreDiabetes, Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT)
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 sitePoland
- Study dates
- 20 Oct 2017to 30 Apr 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- age: 40-65 years;
- pre-diabetic status based on fasting plasma glucose (FPG) and / or OGTT;
- without metformin before;
- without ischemic heart disease in history;
- without a stroke in a history;
- without PAOD (peripheral arterial occlusive disease) in a history;
Show all 14Show fewer
- without active cancer in a history
- age: 40-65 years;
- no carbo-hydrates disturbances (based on fasting plasma glucose (FPG) and/or OGTT);
- without metformin before;
- without ischemic heart disease in history;
- without a stroke in a history;
- without PAOD (peripheral arterial occlusive disease) in a history;
- without active cancer in a history
Who cannot join
- age <40 or >65;
- diabetes;
- taking metformin before study;
- active cancer;
- history of macro-angiopathy (ischemic heart disease, stroke or TIA, PAOD);
- serious gastrointestinal disease that may affect metformin tolerance;
- renal failure with GFR<45 ml/min/1.73m2;
- alanin transaminase > 3 x ULN
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Assessment of the Effect of Metformin and Its Serum Concentration on the Concentration of Substances Associated With the Production of Nitric Oxide in Patients With Impaired Carbohydrate Metabolism
This study evaluates the effect of different doses of metformin on the function of endothelium in people with pre-diabetes. One group of the patients will receive metformin in dose: 1500 mg, the second one will receive 3000 mg/day.
The parameters from healthy volunteers will be taken only at the study beginning to compare the test results with the parameters from patients with pre-diabetes. This group will be not treated with metformin (no intervention)
Read the detailed description
In addition to exercise and diet, metformin is a medicine used to treat diabetes mellitus (DM) and pre-diabetic (pre-DM) conditions. This drug improves insulin sensitivity in both groups of patients (DM and pre-DM) and as a result gives a reduction in blood glucose.
However, studies also confirm the effect of metformin on the reduction of cardiovascular risk in patients with diabetes (UKPDStudy), regardless of the hypoglycaemic effect.
The precise mechanism of action of the drug in this field is not clear. There is also no data on whether similar effects apply to patients with pre-diabetes. Although we know that this group of patients is also characterized by increased cardiovascular risk.
One of the most important substances that are involved in vasodilation is nitric oxide (NO). Impairment of its secretion is an important signal of endothelial damage and is connected with cardiovascular complications.
The impact of metformin on endothelial function in pre-diabetes patients is not known. We do not know the effect of the drug dose and its different serum concentration on the secretion of the dilators of the vessels, which are associated with endothelial function.
The study involves patients with pre-diabetes who meet the inclusion criteria, have no contraindication to participate in the study (see exclusion criteria), and give their written consent after reading "Information for the patient".
The conditions (IFG, IGT) for participation in the study are confirmed by a diabetologist (principal investigator ) based on fasting glucose and OGTT (oral glucose tolerance test) with 75 mg of glucose.
Metformin will be given in an increasing dose in accordance with the test protocol.
After reaching a one-week treatment with a dose of 3 x 500 mg, patients will be assigned to group A -a continuation of a dose of 3 x 500 and group B- increase dose to 3 x 1000mg. Randomization depends on the identification number (ID). The patients with an even, second number in the PESEL (identification number) will be randomized to the A group, the patients with the second, odd number in the PESEL will be randomized to the group B. Here as an example: PESEL: 60010102823-" 0" is as an even number so the patient will be randomized to the group A; PESEL: 61010102823- "1" is an odd number- the patient will be randomized to the group B. This PESEL number (ID) in Poland is given to every person shortly after birth and the researchers have no influence on it.
In the final stage also patients from group B (metformin: 3 x 1000 mg), will back to the treatment dose of metformin 3 x 500 mg- to show the relationship between the dose, serum concentration of the metformin and its effect on the secretion of the measured substances.
The healthy volunteers will be not treated with metformin. Patients will be reminded by phone about the increase in metformin dose as well as on control visits.
The lack of possible treatment with proper doses of metformin due to poor drug tolerance will move the patient from group B to group A if such dose (3 x 500 mg) is well tolerated. The patient will be excluded from the study if no compliance or lack of contact with the patient will be recorded during the treatment period or if metformin dose: 3 x 500 mg will be characterized with bad tolerance.
Information about: age, gender, BMI, cardiovascular risk factors, the current basic lab-tests, and pharmacotherapy will be recorded.
The blood samples for: plasma metformin level and listed substances will be collected for patients with pre-diabetes as described below (see diagram). The basic parameters as well as NO indirect products concentrations will be assessed for healthy volunteers only once-at the beginning of the study.
Test 1: NO(0) (indirect products) for patients before treatment start
3 weeks increasing dose of metformin to the final dose: 1500mg/day
3 x 500 mg (1500/day)- the dose is reached
3 weeks treatment 1500mg/day
Tests 2: NO1(1500) and metformin concentration
Randomization B:3 weeks increasing dose A: 6 weeks continuation with of metformin to the final a dose 3 x 500 mg
dose 3 x 1000mg
3 x 1000mg (3000mg/day)- the dose is reached 3 weeks treatment 3000mg/day Tests 3: NO2(1000) or NO3(500) and metformin concentration for both groups
3 weeks treatment 1500mg/day for both groups
Test 4: NO4 and metformin concentration
Statistical analysis:
For statistical analysis, the Statistica 12 program will be used (StatSoft Polska Sp. z o.o. www.statsoft.pl).
The cut-off point for statistical significance (p) was determined at 0.05. To determine the statistical significance will be used tests compliant with the distribution of variables and data character (Student's t-test, Mann-Whitney test, chi-square test, Kruskal-Wallis ANOVA test). For analysis taking into account the duration of the study and determine the impact of relevant variables to achieve the appropriate concentration of nitric oxide will be used Cox proportional hazard regression. The goal of the optimal determination cut-off point for predictors will use ROC curves. Logistic regression was used to determine the independent predictors to obtain the desired concentration of nitric oxide. In order to determine the correlation, it will be used correlation of order Spearman's rank correlation coefficient or Pearson correlation coefficient.
- Being tested
- Metformin
- Keywords
- prediabetes, impaired fasting glucose, impaired glucose tolerance, metformin, nitric oxide
- Medical subject headings
- Prediabetic State, Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Metformax, Glucophage, Formetic, Siofor
for group A: 12 weeks metformin treatment in a final dose 3 x 500 mg
for group B: 3 weeks metformin treatment in a dose 3 x 500 mg, next: 3 weeks metformin treatment in a final dose 3 x 1000mg, next: 3 weeks metformin treatment in a dose 3 x 500 mg.
| Study group | Role | What they receive |
|---|---|---|
| group A | Other | metformin dose 3 x 500 mg Receives: Drug: Metformin |
| group B | Other | metformin dose 3 x 1000 mg Receives: Drug: Metformin |
| group C | No intervention | healthy volunteers who had basic parameters assessment and blood tests only at the beginning of the study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Levels of Metformin at Different Time Points
the serum concentration of the studied drug-metformin
Measured: 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Serum Levels of Arginine at Different Time Points
arginine serum concentration
Measured: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Serum Levels of ADMA at Different Time Points
ADMA- asymmetric dimethylarginine-serum concentration
Measured: before study start; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Serum Levels of SDMA at Different Time Points
SDMA-symmetric dimethylarginine-serum concentration
Measured: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Serum Levels of Citrulline at Different Time Points
serum concentration of the citrulline
Measured: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Serum Levels of DMA at Different Time Points
DMA- dimethylamine, serum concentration
Measured: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2018
- Study start20 Oct 2017
- Primary completion30 Dec 2018
- Study completion30 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for PreDiabetesStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The group of patients taking the drug at the target dose of 3 x 1000 after 4 weeks returned to the dose of 3 x 500 mg. The group of patients taking the drug at the target dose 3 x 500 mg consequently had this dose during the whole study period. The basic parameters and biochemical parameters from healthy individuals at the beginning of the study were assessed to compare with patients with pre-diabetes. This group did not take the metformin and thus did not have further examination and lab-tests during the study.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wroclaw Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Edyta Sutkowska, Wroclaw Medical University
- Investigators
- Edyta Sutkowska, PhD, Principal investigator, Wroclaw Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03398356
- Sponsor's protocol ID
- ST.C310.17.009
- Status last verified
- May 2022
- First submitted
- 7 Jan 2018
- Last updated
- 27 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data for all primary outcome will be made available.
Publications
IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes: recommendations for standard, comprehensive, and minimal care. Diabet Med. 2006 Jun;23(6):579-93. doi: 10.1111/j.1464-5491.2006.01918.x.
PubMed 16759299Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B; Professional Practice Committee, American Diabetes Association; European Association for the Study of Diabetes. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2006 Aug;49(8):1711-21. doi: 10.1007/s00125-006-0316-2. No abstract available.
PubMed 16802130Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65.
PubMed 9742977Hamed S, Brenner B, Roguin A. Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res. 2011 Jul 1;91(1):9-15. doi: 10.1093/cvr/cvq412. Epub 2010 Dec 24.
PubMed 21186243De Jager J, Kooy A, Lehert P, Bets D, Wulffele MG, Teerlink T, Scheffer PG, Schalkwijk CG, Donker AJ, Stehouwer CD. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2005 Jan;257(1):100-9. doi: 10.1111/j.1365-2796.2004.01420.x.
PubMed 15606381Wisniewski J, Fleszar MG, Piechowicz J, Krzystek-Korpacka M, Chachaj A, Szuba A, Lorenc-Kukula K, Maslowski L, Witkiewicz W, Gamian A. A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS. Biomed Chromatogr. 2017 Nov;31(11). doi: 10.1002/bmc.3994. Epub 2017 May 24.
PubMed 28436051Sutkowska E, Fortuna P, Wisniewski J, Sutkowska K, Hodurek P, Gamian A, Kaluza B. Low metformin dose and its therapeutic serum concentration in prediabetes. Sci Rep. 2021 Jun 3;11(1):11684. doi: 10.1038/s41598-021-91174-7.
PubMed 34083618Sutkowska E, Fortuna P, Kaluza B, Sutkowska K, Wisniewski J, Prof AG. Metformin has no impact on nitric oxide production in patients with pre-diabetes. Biomed Pharmacother. 2021 Aug;140:111773. doi: 10.1016/j.biopha.2021.111773. Epub 2021 May 29.
PubMed 34062418Sutkowska E, Fortuna P, Kaluza B, Sutkowska K, Hodurek P, Fleszar MG. The impact of Sample Handling Time on metformin serum concentration. Biomed Pharmacother. 2021 Jan;133:110971. doi: 10.1016/j.biopha.2020.110971. Epub 2020 Nov 25.
PubMed 33248407
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Assessment of the Effect of Metformin and Its Serum Concentration on the Concentration of Substances Associated With the Production of Nitric Oxide in Patients With Impaired Carbohydrate Metabolism
- ClinicalTrials.gov ID
- NCT03398356
- Acronym / sponsor ID
- ST.C310.17.009
- Keywords
- prediabetes, impaired fasting glucose, impaired glucose tolerance, metformin, nitric oxide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Wroclaw Medical UniversityUniversity, hospital or other
- Study start
- 20 Oct 2017 (actual)
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 12 Jan 2018 (actual)
- Results
- Posted 24 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effect of different doses of metformin on the function of endothelium in people with pre-diabetes. One group of the patients will receive metformin in dose: 1500 mg, the second one will receive 3000 mg/day.
The parameters from healthy volunteers will be taken only at the study beginning to compare the test results with the parameters from patients with pre-diabetes. This group will be not treated with metformin (no intervention)
Detailed description
In addition to exercise and diet, metformin is a medicine used to treat diabetes mellitus (DM) and pre-diabetic (pre-DM) conditions. This drug improves insulin sensitivity in both groups of patients (DM and pre-DM) and as a result gives a reduction in blood glucose.
However, studies also confirm the effect of metformin on the reduction of cardiovascular risk in patients with diabetes (UKPDStudy), regardless of the hypoglycaemic effect.
The precise mechanism of action of the drug in this field is not clear. There is also no data on whether similar effects apply to patients with pre-diabetes. Although we know that this group of patients is also characterized by increased cardiovascular risk.
One of the most important substances that are involved in vasodilation is nitric oxide (NO). Impairment of its secretion is an important signal of endothelial damage and is connected with cardiovascular complications.
The impact of metformin on endothelial function in pre-diabetes patients is not known. We do not know the effect of the drug dose and its different serum concentration on the secretion of the dilators of the vessels, which are associated with endothelial function.
The study involves patients with pre-diabetes who meet the inclusion criteria, have no contraindication to participate in the study (see exclusion criteria), and give their written consent after reading "Information for the patient".
The conditions (IFG, IGT) for participation in the study are confirmed by a diabetologist (principal investigator ) based on fasting glucose and OGTT (oral glucose tolerance test) with 75 mg of glucose.
Metformin will be given in an increasing dose in accordance with the test protocol.
After reaching a one-week treatment with a dose of 3 x 500 mg, patients will be assigned to group A -a continuation of a dose of 3 x 500 and group B- increase dose to 3 x 1000mg. Randomization depends on the identification number (ID). The patients with an even, second number in the PESEL (identification number) will be randomized to the A group, the patients with the second, odd number in the PESEL will be randomized to the group B. Here as an example: PESEL: 60010102823-" 0" is as an even number so the patient will be randomized to the group A; PESEL: 61010102823- "1" is an odd number- the patient will be randomized to the group B. This PESEL number (ID) in Poland is given to every person shortly after birth and the researchers have no influence on it.
In the final stage also patients from group B (metformin: 3 x 1000 mg), will back to the treatment dose of metformin 3 x 500 mg- to show the relationship between the dose, serum concentration of the metformin and its effect on the secretion of the measured substances.
The healthy volunteers will be not treated with metformin. Patients will be reminded by phone about the increase in metformin dose as well as on control visits.
The lack of possible treatment with proper doses of metformin due to poor drug tolerance will move the patient from group B to group A if such dose (3 x 500 mg) is well tolerated. The patient will be excluded from the study if no compliance or lack of contact with the patient will be recorded during the treatment period or if metformin dose: 3 x 500 mg will be characterized with bad tolerance.
Information about: age, gender, BMI, cardiovascular risk factors, the current basic lab-tests, and pharmacotherapy will be recorded.
The blood samples for: plasma metformin level and listed substances will be collected for patients with pre-diabetes as described below (see diagram). The basic parameters as well as NO indirect products concentrations will be assessed for healthy volunteers only once-at the beginning of the study.
Test 1: NO(0) (indirect products) for patients before treatment start
3 weeks increasing dose of metformin to the final dose: 1500mg/day
3 x 500 mg (1500/day)- the dose is reached
3 weeks treatment 1500mg/day
Tests 2: NO1(1500) and metformin concentration
Randomization B:3 weeks increasing dose A: 6 weeks continuation with of metformin to the final a dose 3 x 500 mg
dose 3 x 1000mg
3 x 1000mg (3000mg/day)- the dose is reached 3 weeks treatment 3000mg/day Tests 3: NO2(1000) or NO3(500) and metformin concentration for both groups
3 weeks treatment 1500mg/day for both groups
Test 4: NO4 and metformin concentration
Statistical analysis:
For statistical analysis, the Statistica 12 program will be used (StatSoft Polska Sp. z o.o. www.statsoft.pl).
The cut-off point for statistical significance (p) was determined at 0.05. To determine the statistical significance will be used tests compliant with the distribution of variables and data character (Student's t-test, Mann-Whitney test, chi-square test, Kruskal-Wallis ANOVA test). For analysis taking into account the duration of the study and determine the impact of relevant variables to achieve the appropriate concentration of nitric oxide will be used Cox proportional hazard regression. The goal of the optimal determination cut-off point for predictors will use ROC curves. Logistic regression was used to determine the independent predictors to obtain the desired concentration of nitric oxide. In order to determine the correlation, it will be used correlation of order Spearman's rank correlation coefficient or Pearson correlation coefficient.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 3
- Model description
- The group of patients taking the drug at the target dose of 3 x 1000 after 4 weeks returned to the dose of 3 x 500 mg. The group of patients taking the drug at the target dose 3 x 500 mg consequently had this dose during the whole study period. The basic parameters and biochemical parameters from healthy individuals at the beginning of the study were assessed to compare with patients with pre-diabetes. This group did not take the metformin and thus did not have further examination and lab-tests during the study.
| Arm | Type | Receives |
|---|---|---|
| group A | Other | Drug: Metforminmetformin dose 3 x 500 mg |
| group B | Other | Drug: Metforminmetformin dose 3 x 1000 mg |
| group C | No intervention | –healthy volunteers who had basic parameters assessment and blood tests only at the beginning of the study |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- age: 40-65 years;
- pre-diabetic status based on fasting plasma glucose (FPG) and / or OGTT;
- without metformin before;
- without ischemic heart disease in history;
- without a stroke in a history;
Key exclusion criteria (8 listed)
- age <40 or >65;
- diabetes;
- taking metformin before study;
- active cancer;
- history of macro-angiopathy (ischemic heart disease, stroke or TIA, PAOD);
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 |
|---|---|---|
| MetforminAlso: Metformax, Glucophage, Formetic, Sioforfor group A: 12 weeks metformin treatment in a final dose 3 x 500 mg for group B: 3 weeks metformin treatment in a dose 3 x 500 mg, next: 3 weeks metformin treatment in a final dose 3 x 1000mg, next: 3 weeks metformin treatment in a dose 3 x 500 mg. | Drug | group A, group B |
Primary outcome
Serum Levels of Metformin at Different Time Points
Time frame: 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
the serum concentration of the studied drug-metformin
Serum Levels of Arginine at Different Time Points
Time frame: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
arginine serum concentration
Serum Levels of ADMA at Different Time Points
Time frame: before study start; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
ADMA- asymmetric dimethylarginine-serum concentration
Serum Levels of SDMA at Different Time Points
Time frame: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
SDMA-symmetric dimethylarginine-serum concentration
Serum Levels of Citrulline at Different Time Points
Time frame: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
serum concentration of the citrulline
Serum Levels of DMA at Different Time Points
Time frame: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
DMA- dimethylamine, serum concentration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16759299IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes: recommendations for standard, comprehensive, and minimal care. Diabet Med. 2006 Jun;23(6):579-93. doi: 10.1111/j.1464-5491.2006.01918.x.
- Background: PubMed 16802130Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B; Professional Practice Committee, American Diabetes Association; European Association for the Study of Diabetes. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2006 Aug;49(8):1711-21. doi: 10.1007/s00125-006-0316-2. No abstract available.
- Background: PubMed 9742977Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65.
- Background: PubMed 21186243Hamed S, Brenner B, Roguin A. Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res. 2011 Jul 1;91(1):9-15. doi: 10.1093/cvr/cvq412. Epub 2010 Dec 24.
- Background: PubMed 15606381De Jager J, Kooy A, Lehert P, Bets D, Wulffele MG, Teerlink T, Scheffer PG, Schalkwijk CG, Donker AJ, Stehouwer CD. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2005 Jan;257(1):100-9. doi: 10.1111/j.1365-2796.2004.01420.x.
- Background: PubMed 28436051Wisniewski J, Fleszar MG, Piechowicz J, Krzystek-Korpacka M, Chachaj A, Szuba A, Lorenc-Kukula K, Maslowski L, Witkiewicz W, Gamian A. A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS. Biomed Chromatogr. 2017 Nov;31(11). doi: 10.1002/bmc.3994. Epub 2017 May 24.
- Results publication: PubMed 34083618Sutkowska E, Fortuna P, Wisniewski J, Sutkowska K, Hodurek P, Gamian A, Kaluza B. Low metformin dose and its therapeutic serum concentration in prediabetes. Sci Rep. 2021 Jun 3;11(1):11684. doi: 10.1038/s41598-021-91174-7.
- Results publication: PubMed 34062418Sutkowska E, Fortuna P, Kaluza B, Sutkowska K, Wisniewski J, Prof AG. Metformin has no impact on nitric oxide production in patients with pre-diabetes. Biomed Pharmacother. 2021 Aug;140:111773. doi: 10.1016/j.biopha.2021.111773. Epub 2021 May 29.
- Results publication: PubMed 33248407Sutkowska E, Fortuna P, Kaluza B, Sutkowska K, Hodurek P, Fleszar MG. The impact of Sample Handling Time on metformin serum concentration. Biomed Pharmacother. 2021 Jan;133:110971. doi: 10.1016/j.biopha.2020.110971. Epub 2020 Nov 25.
- Individual participant dataSharing planned: Yes. De-identified individual participant data for all primary outcome will be made available.
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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.
Edyta Sutkowska, PhD principal investigator
Wroclaw Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with PreDiabetes and Impaired Fasting Glucose (IFG), run by Wroclaw Medical University at 1 site in Poland.
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 14 inclusion and 8 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 27 May 2022. 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 Poland. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Serum Levels of Metformin at Different Time Points (time frame: 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start). The study lists 6 primary outcomes in all. 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 NCT03398356, which also lists 9 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 27 May 2022.