Trial Outcomes & Findings for Metformin and Its Impact on the Substances Associated With NO Production in Prediabetes Patients. (NCT NCT03398356)
NCT ID: NCT03398356
Last Updated: 2022-05-27
Results Overview
the serum concentration of the studied drug-metformin
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
47 participants
Primary outcome timeframe
6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start
Results posted on
2022-05-27
Participant Flow
Participant milestones
| Measure |
Group B
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
Group A
metformin dose 3 x 500 mg
Metformin: 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.
|
|---|---|---|---|
|
Before Treatment
STARTED
|
21
|
11
|
15
|
|
Before Treatment
COMPLETED
|
13
|
0
|
12
|
|
Before Treatment
NOT COMPLETED
|
8
|
11
|
3
|
|
After 6 Weeks of Treatment
STARTED
|
13
|
0
|
12
|
|
After 6 Weeks of Treatment
COMPLETED
|
11
|
0
|
12
|
|
After 6 Weeks of Treatment
NOT COMPLETED
|
2
|
0
|
0
|
|
Post 6 Week Period Initial Evaluation
STARTED
|
11
|
0
|
14
|
|
Post 6 Week Period Initial Evaluation
COMPLETED
|
11
|
0
|
14
|
|
Post 6 Week Period Initial Evaluation
NOT COMPLETED
|
0
|
0
|
0
|
|
After 12 Weeks of Treatment
STARTED
|
11
|
0
|
14
|
|
After 12 Weeks of Treatment
COMPLETED
|
11
|
0
|
14
|
|
After 12 Weeks of Treatment
NOT COMPLETED
|
0
|
0
|
0
|
|
After 15 Weeks of Treatment
STARTED
|
11
|
0
|
14
|
|
After 15 Weeks of Treatment
COMPLETED
|
11
|
0
|
14
|
|
After 15 Weeks of Treatment
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Group B
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
Group A
metformin dose 3 x 500 mg
Metformin: 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.
|
|---|---|---|---|
|
Before Treatment
Lost to Follow-up
|
2
|
0
|
1
|
|
Before Treatment
drug intolerance
|
1
|
0
|
2
|
|
Before Treatment
Withdrawal by Subject
|
5
|
0
|
0
|
|
Before Treatment
Physician Decision
|
0
|
11
|
0
|
|
After 6 Weeks of Treatment
Physician Decision
|
2
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Group A
n=14 Participants
Patients with pre-diabetes; metformin dose 3 x 500 mg
Metformin: for group A: 12 weeks metformin treatment with a final dose 3 x 500 mg, after 3 weeks of the titration Total treatment time: 15 weeks
|
Group B
n=11 Participants
Patients with pre-diabetes, max metformin dose 3 x 1000 mg
Metformin: for group B: 3 weeks metformin treatment with a dose 3 x 500 mg, after 3 weeks of the titration next: 3 weeks metformin treatment with a final dose 3 x 1000mg, after 3 weeks of the titration next: 3 weeks metformin treatment with a dose 3 x 500 mg. Total treatment time: 15 weeks
|
Group C
n=11 Participants
healthy volunteers
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
50.64 years
STANDARD_DEVIATION 8.85 • n=14 Participants
|
55.73 years
STANDARD_DEVIATION 8.27 • n=11 Participants
|
49.90 years
STANDARD_DEVIATION 8.37 • n=11 Participants
|
51.97 years
STANDARD_DEVIATION 8.67 • n=36 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=14 Participants
|
3 Participants
n=11 Participants
|
6 Participants
n=11 Participants
|
14 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=14 Participants
|
8 Participants
n=11 Participants
|
5 Participants
n=11 Participants
|
22 Participants
n=36 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Poland
|
14 Participants
n=14 Participants
|
11 Participants
n=11 Participants
|
11 Participants
n=11 Participants
|
36 Participants
n=36 Participants
|
|
BMI
|
31.49 kg/m^2
STANDARD_DEVIATION 5.26 • n=14 Participants
|
30.75 kg/m^2
STANDARD_DEVIATION 4 • n=11 Participants
|
26.99 kg/m^2
STANDARD_DEVIATION 5.43 • n=11 Participants
|
29.89 kg/m^2
STANDARD_DEVIATION 5.21 • n=36 Participants
|
|
body mass
|
96.71 kg
STANDARD_DEVIATION 13.74 • n=14 Participants
|
92.36 kg
STANDARD_DEVIATION 9.73 • n=11 Participants
|
80.81 kg
STANDARD_DEVIATION 20.64 • n=11 Participants
|
90.52 kg
STANDARD_DEVIATION 16.28 • n=36 Participants
|
|
creatinine
|
0.86 mg/dl
STANDARD_DEVIATION 0.18 • n=14 Participants
|
0.89 mg/dl
STANDARD_DEVIATION 0.16 • n=11 Participants
|
0.73 mg/dl
STANDARD_DEVIATION 0.03 • n=11 Participants
|
0.85 mg/dl
STANDARD_DEVIATION 0.16 • n=36 Participants
|
|
alanin transaminase
|
28.13 U/l
STANDARD_DEVIATION 14.01 • n=14 Participants
|
35.45 U/l
STANDARD_DEVIATION 20.51 • n=11 Participants
|
19.11 U/l
STANDARD_DEVIATION 12.06 • n=11 Participants
|
28.11 U/l
STANDARD_DEVIATION 16.74 • n=36 Participants
|
|
TCL- total cholesterol level
|
207.21 mg/dl
STANDARD_DEVIATION 50.22 • n=14 Participants
|
184.91 mg/dl
STANDARD_DEVIATION 34.19 • n=11 Participants
|
201 mg/dl
STANDARD_DEVIATION 27.47 • n=11 Participants
|
198.50 mg/dl
STANDARD_DEVIATION 39.71 • n=36 Participants
|
|
TG-triglicerydes
|
133.29 mg/dl
STANDARD_DEVIATION 62.77 • n=14 Participants
|
136.82 mg/dl
STANDARD_DEVIATION 66.63 • n=11 Participants
|
137.09 mg/dl
STANDARD_DEVIATION 49.20 • n=11 Participants
|
135.53 mg/dl
STANDARD_DEVIATION 58.54 • n=36 Participants
|
|
HDL- high density lipoprotein
|
49.86 mg/dl
STANDARD_DEVIATION 12.07 • n=14 Participants
|
50.73 mg/dl
STANDARD_DEVIATION 14.35 • n=11 Participants
|
57.91 mg/dl
STANDARD_DEVIATION 16.82 • n=11 Participants
|
52.58 mg/dl
STANDARD_DEVIATION 14.38 • n=36 Participants
|
|
LDL-low density lipoprotein
|
125.29 mg/dl
STANDARD_DEVIATION 30.79 • n=14 Participants
|
106.95 mg/dl
STANDARD_DEVIATION 23.78 • n=11 Participants
|
115.70 mg/dl
STANDARD_DEVIATION 19.91 • n=11 Participants
|
116.75 mg/dl
STANDARD_DEVIATION 26.20 • n=36 Participants
|
|
Fasting Plasma Glucose (FPG)
|
109.39 mg/dl
STANDARD_DEVIATION 11.13 • n=14 Participants
|
107.23 mg/dl
STANDARD_DEVIATION 5.95 • n=11 Participants
|
88.81 mg/dl
STANDARD_DEVIATION 4.44 • n=11 Participants
|
102.44 mg/dl
STANDARD_DEVIATION 12.11 • n=36 Participants
|
|
liver steatosis
|
7 Participants
n=14 Participants
|
9 Participants
n=11 Participants
|
1 Participants
n=11 Participants
|
17 Participants
n=36 Participants
|
|
nicotinism
|
3 Participants
n=14 Participants
|
4 Participants
n=11 Participants
|
2 Participants
n=11 Participants
|
9 Participants
n=36 Participants
|
|
hypertension
|
7 Participants
n=14 Participants
|
6 Participants
n=11 Participants
|
3 Participants
n=11 Participants
|
16 Participants
n=36 Participants
|
|
family history for DM
|
7 Participants
n=14 Participants
|
4 Participants
n=11 Participants
|
3 Participants
n=11 Participants
|
14 Participants
n=36 Participants
|
|
arginine
|
114.29 µM
STANDARD_DEVIATION 28.15 • n=14 Participants
|
110.37 µM
STANDARD_DEVIATION 27.63 • n=11 Participants
|
122.11 µM
STANDARD_DEVIATION 27.96 • n=11 Participants
|
115.48 µM
STANDARD_DEVIATION 27.54 • n=36 Participants
|
|
ADMA
|
0.51 µM
STANDARD_DEVIATION 0.09 • n=14 Participants
|
0.53 µM
STANDARD_DEVIATION 0.09 • n=11 Participants
|
0.56 µM
STANDARD_DEVIATION 0.10 • n=11 Participants
|
0.53 µM
STANDARD_DEVIATION 0.09 • n=36 Participants
|
|
SDMA
|
0.39 µM
STANDARD_DEVIATION 0.07 • n=14 Participants
|
0.41 µM
STANDARD_DEVIATION 0.10 • n=11 Participants
|
0.42 µM
STANDARD_DEVIATION 0.08 • n=11 Participants
|
0.41 µM
STANDARD_DEVIATION 0.08 • n=36 Participants
|
|
DMA
|
1.77 µM
STANDARD_DEVIATION 0.71 • n=14 Participants
|
1.74 µM
STANDARD_DEVIATION 0.48 • n=11 Participants
|
1.67 µM
STANDARD_DEVIATION 0.40 • n=11 Participants
|
1.73 µM
STANDARD_DEVIATION 0.55 • n=36 Participants
|
|
Citrulline
|
34.10 µM
STANDARD_DEVIATION 9.84 • n=14 Participants
|
38.33 µM
STANDARD_DEVIATION 7.49 • n=11 Participants
|
36.45 µM
STANDARD_DEVIATION 8.82 • n=11 Participants
|
36.11 µM
STANDARD_DEVIATION 8.8 • n=36 Participants
|
|
Ornithine
|
34.77 µM
STANDARD_DEVIATION 11.58 • n=14 Participants
|
37.12 µM
STANDARD_DEVIATION 15.71 • n=11 Participants
|
35.57 µM
STANDARD_DEVIATION 11.09 • n=11 Participants
|
35.73 µM
STANDARD_DEVIATION 12.51 • n=36 Participants
|
PRIMARY outcome
Timeframe: 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment startPopulation: Group A and B- patients with pre-diabetes treated with different metformin dose (according to the information above as arm description) , group C- healthy volunteers, no metformin assessment as no treatment
the serum concentration of the studied drug-metformin
Outcome measures
| Measure |
Group A
n=14 Participants
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=11 Participants
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
|---|---|---|---|
|
Serum Levels of Metformin at Different Time Points
6 weeks from the start of treatment
|
4.36 µM
Standard Deviation 2.36
|
4.25 µM
Standard Deviation 2.58
|
—
|
|
Serum Levels of Metformin at Different Time Points
12 weeks from the start of treatment
|
5.09 µM
Standard Deviation 2.29
|
7.42 µM
Standard Deviation 4.77
|
—
|
|
Serum Levels of Metformin at Different Time Points
15 weeks from the start of treatment
|
4.66 µM
Standard Deviation 3.73
|
4.01 µM
Standard Deviation 4.01
|
—
|
PRIMARY outcome
Timeframe: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment startPopulation: Groups A and B -patients with pre-diabetes treated with different dose of the metformin, group C- healthy volunteers, no metformin
arginine serum concentration
Outcome measures
| Measure |
Group A
n=14 Participants
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=11 Participants
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
|---|---|---|---|
|
Serum Levels of Arginine at Different Time Points
6 weeks from the start of treatment
|
112.18 µM
Standard Deviation 53.42
|
111.72 µM
Standard Deviation 36.89
|
—
|
|
Serum Levels of Arginine at Different Time Points
12 weeks from the start of treatment
|
107.72 µM
Standard Deviation 13.93
|
97.69 µM
Standard Deviation 38.76
|
—
|
|
Serum Levels of Arginine at Different Time Points
15 weeks from the start of treatment
|
104.72 µM
Standard Deviation 34.21
|
103.76 µM
Standard Deviation 19.76
|
—
|
PRIMARY outcome
Timeframe: before study start; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment startPopulation: Groups A and B -patients with pre-diabetes treated with different dose of the metformin, group C- healthy volunteers, no metformin
ADMA- asymmetric dimethylarginine-serum concentration
Outcome measures
| Measure |
Group A
n=14 Participants
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=11 Participants
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
|---|---|---|---|
|
Serum Levels of ADMA at Different Time Points
6 weeks from the start of treatment
|
0.51 µM
Standard Deviation 0.11
|
0.57 µM
Standard Deviation 0.11
|
—
|
|
Serum Levels of ADMA at Different Time Points
12 weeks from the start of treatment
|
0.52 µM
Standard Deviation 0.09
|
0.55 µM
Standard Deviation 0.14
|
—
|
|
Serum Levels of ADMA at Different Time Points
15 weeks from the start of treatment
|
0.50 µM
Standard Deviation 0.08
|
0.52 µM
Standard Deviation 0.10
|
—
|
PRIMARY outcome
Timeframe: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment startPopulation: Groups A and B -patients with pre-diabetes treated with different dose of the metformin, group C- healthy volunteers, no metformin
SDMA-symmetric dimethylarginine-serum concentration
Outcome measures
| Measure |
Group A
n=14 Participants
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=11 Participants
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
|---|---|---|---|
|
Serum Levels of SDMA at Different Time Points
6 weeks from the start of treatment
|
0.40 µM
Standard Deviation 0.08
|
0.45 µM
Standard Deviation 0.08
|
—
|
|
Serum Levels of SDMA at Different Time Points
12 weeks from the start of treatment
|
0.41 µM
Standard Deviation 0.08
|
0.42 µM
Standard Deviation 0.08
|
—
|
|
Serum Levels of SDMA at Different Time Points
15 weeks from the start of treatment
|
0.39 µM
Standard Deviation 0.07
|
0.39 µM
Standard Deviation 0.06
|
—
|
PRIMARY outcome
Timeframe: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment startPopulation: Groups A and B -patients with pre-diabetes treated with different dose of the metformin, group C- healthy volunteers, no metformin
serum concentration of the citrulline
Outcome measures
| Measure |
Group A
n=14 Participants
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=11 Participants
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
|---|---|---|---|
|
Serum Levels of Citrulline at Different Time Points
6 weeks from the start of treatment
|
21.73 µM
Standard Deviation 6.66
|
28.08 µM
Standard Deviation 11.31
|
—
|
|
Serum Levels of Citrulline at Different Time Points
12 weeks from the start of treatment
|
25.95 µM
Standard Deviation 9.48
|
27.01 µM
Standard Deviation 15.38
|
—
|
|
Serum Levels of Citrulline at Different Time Points
15 weeks from the start of treatment
|
26.93 µM
Standard Deviation 9.71
|
29.77 µM
Standard Deviation 11.26
|
—
|
PRIMARY outcome
Timeframe: Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment startPopulation: Groups A and B -patients with pre-diabetes treated with different dose of the metformin, group C- healthy volunteers, no metformin
DMA- dimethylamine, serum concentration
Outcome measures
| Measure |
Group A
n=14 Participants
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=11 Participants
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
control healthy volunteers, no intervention
|
|---|---|---|---|
|
Serum Levels of DMA at Different Time Points
6 weeks from the start of treatment
|
1.71 µM
Standard Deviation 0.31
|
2.07 µM
Standard Deviation 0.52
|
—
|
|
Serum Levels of DMA at Different Time Points
12 weeks from the start of treatment
|
1.63 µM
Standard Deviation 0.28
|
1.89 µM
Standard Deviation 0.43
|
—
|
|
Serum Levels of DMA at Different Time Points
15 weeks from the start of treatment
|
1.62 µM
Standard Deviation 0.34
|
1.84 µM
Standard Deviation 0.68
|
—
|
Adverse Events
Group A
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Group B
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Group C
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group A
n=15 participants at risk
metformin dose 3 x 500 mg
Metformin: 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.
|
Group B
n=21 participants at risk
metformin dose 3 x 1000 mg
Metformin: 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.
|
Group C
n=11 participants at risk
healthy volunteers, no intervention
|
|---|---|---|---|
|
Gastrointestinal disorders
drug intolerance
|
20.0%
3/15 • Number of events 3 • 15 weeks
Other- important gastrointestinal side effects which did not allow the prescribed dose to be continued
|
9.5%
2/21 • Number of events 2 • 15 weeks
Other- important gastrointestinal side effects which did not allow the prescribed dose to be continued
|
0.00%
0/11 • 15 weeks
Other- important gastrointestinal side effects which did not allow the prescribed dose to be continued
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place