Trial Outcomes & Findings for Antecedent Metabolic Health and Metformin Aging Study (NCT NCT04264897)
NCT ID: NCT04264897
Last Updated: 2026-07-02
Results Overview
Insulin Sensitivity Index = M / I x 1000. M = Glucose disposal rate (mg/min), normalized to fat-free mass (kg). I = insulin concentration (mU/L) during steady state of the clamp (based on glucose infusion rate). We rely on the delta (post-pre) of the insulin sensitivity index as our primary outcome. Positive delta values indicate improved insulin sensitivity (a positive outcome), while negative delta values indicate lower insulin sensitivity (a negative outcome). Insulin sensitivity cannot be physiologically zero or negative. Maximum negative change insulin sensitivity index = -52.31 mg/kg FFM/min/mU/L. Maximum positive insulin sensitivity index = 42.32 mg/kg FFM/min/mU/L.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
166 participants
Primary outcome timeframe
Change from baseline to 12 weeks
Results posted on
2026-07-02
Participant Flow
Participants were recruited from 2 sites: The Oklahoma Medical Research Foundation/University of Oklahoma Health Sciences Center and the University of Wisconsin-Madison.
Three hundred and sixty participants were phone screened, of whom 166 signed the informed consent. Of the 166 who signed the consent, 101 subjects completed the study. Subjects were randomized based on Baseline HOMA-IR (Placebo-IS = 48, Placebo-IR = 31, Metformin-IS = 52, and Metformin-IR = 35) but were re-assigned based on GIR (mg/kg FFM/min/mU/L) for statistical analyses (Placebo-IS = 24, Placebo-IR = 23, Metformin-IS = 27, and Metformin-IR = 27).
Participant milestones
| Measure |
Placebo - Insulin Sensitive
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
48
|
31
|
52
|
35
|
|
Overall Study
HOMA-IR Based Population - Completed
|
27
|
20
|
33
|
21
|
|
Overall Study
Re-Distribution of Subjects for Insulin Sensitivity Index-Based Analyses Population
|
24
|
23
|
27
|
27
|
|
Overall Study
COMPLETED
|
27
|
20
|
33
|
21
|
|
Overall Study
NOT COMPLETED
|
21
|
11
|
19
|
14
|
Reasons for withdrawal
| Measure |
Placebo - Insulin Sensitive
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
7
|
8
|
5
|
2
|
|
Overall Study
Investigator Decision
|
10
|
0
|
7
|
0
|
|
Overall Study
Failed Inclusion Criteria
|
4
|
3
|
5
|
12
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
Baseline Characteristics
This measure was used for re-stratification of subjects based on metabolic status (insulin sensitive or insulin resistant) and serves as baseline measure. The number of subjects per group is lower due to failed hyperinsulinemic euglycemic clamp procedure.
Baseline characteristics by cohort
| Measure |
Placebo - Insulin Sensitive
n=24 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
n=23 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
n=27 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
n=27 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Total
n=101 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
Age
|
57 Years
STANDARD_DEVIATION 8 • n=24 Participants
|
57 Years
STANDARD_DEVIATION 10 • n=23 Participants
|
57 Years
STANDARD_DEVIATION 9 • n=27 Participants
|
56 Years
STANDARD_DEVIATION 10 • n=27 Participants
|
57 Years
STANDARD_DEVIATION 10 • n=101 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=24 Participants
|
18 Participants
n=23 Participants
|
18 Participants
n=27 Participants
|
15 Participants
n=27 Participants
|
61 Participants
n=101 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=24 Participants
|
5 Participants
n=23 Participants
|
9 Participants
n=27 Participants
|
12 Participants
n=27 Participants
|
40 Participants
n=101 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=24 Participants
|
3 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=27 Participants
|
6 Participants
n=101 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=24 Participants
|
1 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=101 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=24 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=101 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=24 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=101 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=24 Participants
|
17 Participants
n=23 Participants
|
26 Participants
n=27 Participants
|
20 Participants
n=27 Participants
|
81 Participants
n=101 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=24 Participants
|
2 Participants
n=23 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=27 Participants
|
6 Participants
n=101 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=24 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=101 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=24 Participants
|
1 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=101 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=24 Participants
|
22 Participants
n=23 Participants
|
27 Participants
n=27 Participants
|
27 Participants
n=27 Participants
|
99 Participants
n=101 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=24 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=101 Participants
|
|
Body Mass Index (BMI)
|
27.4 kg/(m^2)
STANDARD_DEVIATION 4.8 • n=24 Participants
|
31.9 kg/(m^2)
STANDARD_DEVIATION 6.4 • n=23 Participants
|
28.0 kg/(m^2)
STANDARD_DEVIATION 6.3 • n=27 Participants
|
32.2 kg/(m^2)
STANDARD_DEVIATION 6.5 • n=27 Participants
|
29.9 kg/(m^2)
STANDARD_DEVIATION 6.3 • n=101 Participants
|
|
Precent Body Fat
|
34.14 %
STANDARD_DEVIATION 12.78 • n=24 Participants
|
42.52 %
STANDARD_DEVIATION 7.05 • n=23 Participants
|
36.61 %
STANDARD_DEVIATION 10.13 • n=27 Participants
|
40.18 %
STANDARD_DEVIATION 7.36 • n=27 Participants
|
37.61 %
STANDARD_DEVIATION 10.35 • n=101 Participants
|
|
Fat Mass
|
38.3 kg
STANDARD_DEVIATION 18.1 • n=24 Participants
|
36.1 kg
STANDARD_DEVIATION 10.8 • n=23 Participants
|
29.4 kg
STANDARD_DEVIATION 12.7 • n=27 Participants
|
37.4 kg
STANDARD_DEVIATION 12.8 • n=27 Participants
|
32.8 kg
STANDARD_DEVIATION 14.2 • n=101 Participants
|
|
Fat Free Mass
|
54.0 kg
STANDARD_DEVIATION 9.7 • n=24 Participants
|
48.1 kg
STANDARD_DEVIATION 8.3 • n=23 Participants
|
51.0 kg
STANDARD_DEVIATION 13.1 • n=27 Participants
|
54.7 kg
STANDARD_DEVIATION 11.9 • n=27 Participants
|
52.1 kg
STANDARD_DEVIATION 11.2 • n=101 Participants
|
|
Fasting A1C
|
5.3 Precentage
STANDARD_DEVIATION 0.3 • n=24 Participants
|
5.5 Precentage
STANDARD_DEVIATION 0.3 • n=23 Participants
|
5.5 Precentage
STANDARD_DEVIATION 0.3 • n=27 Participants
|
5.6 Precentage
STANDARD_DEVIATION 0.3 • n=27 Participants
|
5.5 Precentage
STANDARD_DEVIATION 0.3 • n=101 Participants
|
|
Fasting Blood Glucose
|
93 mg/dL
STANDARD_DEVIATION 8 • n=24 Participants
|
97 mg/dL
STANDARD_DEVIATION 9 • n=23 Participants
|
93 mg/dL
STANDARD_DEVIATION 9 • n=27 Participants
|
93 mg/dL
STANDARD_DEVIATION 10 • n=27 Participants
|
94.0 mg/dL
STANDARD_DEVIATION 9.0 • n=101 Participants
|
|
HOMA-IR
|
1.65 Index
STANDARD_DEVIATION 1.26 • n=24 Participants
|
2.41 Index
STANDARD_DEVIATION 1.08 • n=23 Participants
|
1.29 Index
STANDARD_DEVIATION 0.64 • n=27 Participants
|
2.81 Index
STANDARD_DEVIATION 12.8 • n=27 Participants
|
2.03 Index
STANDARD_DEVIATION 1.50 • n=101 Participants
|
|
Baseline Insulin Sensitivity Index
|
37.2 mg/kg FFM/min/mU/L
STANDARD_DEVIATION 14.8 • n=21 Participants • This measure was used for re-stratification of subjects based on metabolic status (insulin sensitive or insulin resistant) and serves as baseline measure. The number of subjects per group is lower due to failed hyperinsulinemic euglycemic clamp procedure.
|
14.1 mg/kg FFM/min/mU/L
STANDARD_DEVIATION 3.9 • n=21 Participants • This measure was used for re-stratification of subjects based on metabolic status (insulin sensitive or insulin resistant) and serves as baseline measure. The number of subjects per group is lower due to failed hyperinsulinemic euglycemic clamp procedure.
|
34.8 mg/kg FFM/min/mU/L
STANDARD_DEVIATION 7.8 • n=25 Participants • This measure was used for re-stratification of subjects based on metabolic status (insulin sensitive or insulin resistant) and serves as baseline measure. The number of subjects per group is lower due to failed hyperinsulinemic euglycemic clamp procedure.
|
14.0 mg/kg FFM/min/mU/L
STANDARD_DEVIATION 5.9 • n=25 Participants • This measure was used for re-stratification of subjects based on metabolic status (insulin sensitive or insulin resistant) and serves as baseline measure. The number of subjects per group is lower due to failed hyperinsulinemic euglycemic clamp procedure.
|
24.9 mg/kg FFM/min/mU/L
STANDARD_DEVIATION 14.1 • n=92 Participants • This measure was used for re-stratification of subjects based on metabolic status (insulin sensitive or insulin resistant) and serves as baseline measure. The number of subjects per group is lower due to failed hyperinsulinemic euglycemic clamp procedure.
|
PRIMARY outcome
Timeframe: Change from baseline to 12 weeksPopulation: Change in Insulin Sensitivity Index, Continuous (mg/kg Fat Free Mass/min/mU/L) from pre to post measures. This population includes those subjects who had both a pre- and post-hyperinsulinemic-euglycemic clamp.
Insulin Sensitivity Index = M / I x 1000. M = Glucose disposal rate (mg/min), normalized to fat-free mass (kg). I = insulin concentration (mU/L) during steady state of the clamp (based on glucose infusion rate). We rely on the delta (post-pre) of the insulin sensitivity index as our primary outcome. Positive delta values indicate improved insulin sensitivity (a positive outcome), while negative delta values indicate lower insulin sensitivity (a negative outcome). Insulin sensitivity cannot be physiologically zero or negative. Maximum negative change insulin sensitivity index = -52.31 mg/kg FFM/min/mU/L. Maximum positive insulin sensitivity index = 42.32 mg/kg FFM/min/mU/L.
Outcome measures
| Measure |
Placebo - Insulin Sensitive
n=19 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
n=19 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
n=21 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
n=23 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|---|---|
|
Mean Change in Insulin Sensitivity Index
|
-6.3 mg/kg Fat Free Mass/min/mU/L
Standard Deviation 17.9
|
1.8 mg/kg Fat Free Mass/min/mU/L
Standard Deviation 8.8
|
-4.5 mg/kg Fat Free Mass/min/mU/L
Standard Deviation 9.7
|
2.1 mg/kg Fat Free Mass/min/mU/L
Standard Deviation 4.8
|
PRIMARY outcome
Timeframe: Change from baseline to 12 weeksPopulation: This subject population included those who had a pre- and post skeletal muscle biopsy.
Mitochondrial respiration was measured using permeabilized muscle fibers from the vastus lateralis using high-resolution respirometry. We rely on the delta (change from post-pre) of the Complex I mitochondrial respiratory capacity. Positive values indicate an increase in mitochondrial respiratory capacity and improved outcomes, while negative values indicate a reduction in mitochondrial respiratory capacity and a negative outcome. There is no minimum or maximum reported for mitochondrial respiratory capacity of CI, but mitochondrial respiratory capacity of CI cannot physiologically be zero or negative. We and others have previously reported maximal complex I linked oxidative phosphorylation at approximately 250 pmol/mg of tissue/s in ultra-endurance athletes.
Outcome measures
| Measure |
Placebo - Insulin Sensitive
n=21 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
n=19 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
n=24 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
n=23 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|---|---|
|
Mean Change in Mitochondrial Function of the Electron Transport System Measured by Complex I Activity
|
0.99 pmol/mg/s
Standard Deviation 15.95
|
0.48 pmol/mg/s
Standard Deviation 11.79
|
-5.98 pmol/mg/s
Standard Deviation 22.27
|
-2.57 pmol/mg/s
Standard Deviation 13.67
|
SECONDARY outcome
Timeframe: Change from baseline to 12 weeksPopulation: This analyses includes those subjects who had a pre- and post continuous glucose monitor.
5-day continuous glucose monitoring
Outcome measures
| Measure |
Placebo - Insulin Sensitive
n=16 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
n=14 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
n=19 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
n=13 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|---|---|
|
Mean Change in Daily Average Glucose Measure
|
0.3 Change in Average Daily Glucose (mg/DL)
Standard Deviation 9.3
|
0.8 Change in Average Daily Glucose (mg/DL)
Standard Deviation 16.9
|
-0.4 Change in Average Daily Glucose (mg/DL)
Standard Deviation 10.6
|
-8.3 Change in Average Daily Glucose (mg/DL)
Standard Deviation 11.1
|
SECONDARY outcome
Timeframe: Change from baseline to 12 weeksThis blood-based biomarker panel, developed by LeBrasseur and colleagues, measures changes in senescence-associated secretory phenotype proteins. This panel is associated with chronological age, biological age, and adverse clinical outcomes. Changes in the protein levels of biomarkers reflect changes in biological age. A greater abundance in these biomarkers is associated with greater frailty or biological aging. We rely on the delta (change from post-pre) of the biological markers. A positive value is associated with a negative outcome, while a negative value is associated with a positive outcome.
Outcome measures
| Measure |
Placebo - Insulin Sensitive
n=18 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Placebo - Insulin Resistant
n=19 Participants
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Sensitive
n=24 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin - Insulin Resistant
n=21 Participants
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|---|---|
|
Mean Change in Blood-based Biomarker Measures of Aging
MMP-1
|
386 Protein Expression (relative units)
Standard Deviation 929
|
-651 Protein Expression (relative units)
Standard Deviation 1681
|
80 Protein Expression (relative units)
Standard Deviation 530
|
609 Protein Expression (relative units)
Standard Deviation 1343
|
|
Mean Change in Blood-based Biomarker Measures of Aging
MPO
|
-9442 Protein Expression (relative units)
Standard Deviation 44571
|
1720 Protein Expression (relative units)
Standard Deviation 94137
|
59345 Protein Expression (relative units)
Standard Deviation 176257
|
-31943 Protein Expression (relative units)
Standard Deviation 139016
|
|
Mean Change in Blood-based Biomarker Measures of Aging
IL-6
|
0.14 Protein Expression (relative units)
Standard Deviation 1.12
|
-0.06 Protein Expression (relative units)
Standard Deviation 1.00
|
0.73 Protein Expression (relative units)
Standard Deviation 3.5
|
-0.02 Protein Expression (relative units)
Standard Deviation 1.10
|
|
Mean Change in Blood-based Biomarker Measures of Aging
PAI-1
|
1151 Protein Expression (relative units)
Standard Deviation 27000
|
-12129 Protein Expression (relative units)
Standard Deviation 38693
|
-3444 Protein Expression (relative units)
Standard Deviation 27222
|
16407 Protein Expression (relative units)
Standard Deviation 38436
|
|
Mean Change in Blood-based Biomarker Measures of Aging
Eotaxin
|
10 Protein Expression (relative units)
Standard Deviation 58
|
-14 Protein Expression (relative units)
Standard Deviation 31
|
2 Protein Expression (relative units)
Standard Deviation 34
|
16 Protein Expression (relative units)
Standard Deviation 40
|
|
Mean Change in Blood-based Biomarker Measures of Aging
ActivinA
|
-11 Protein Expression (relative units)
Standard Deviation 41
|
-6 Protein Expression (relative units)
Standard Deviation 42
|
-22 Protein Expression (relative units)
Standard Deviation 54
|
-10 Protein Expression (relative units)
Standard Deviation 57
|
|
Mean Change in Blood-based Biomarker Measures of Aging
ADAMTS13
|
-7161 Protein Expression (relative units)
Standard Deviation 1032212
|
30842 Protein Expression (relative units)
Standard Deviation 131318
|
13147 Protein Expression (relative units)
Standard Deviation 81801
|
920 Protein Expression (relative units)
Standard Deviation 167172
|
|
Mean Change in Blood-based Biomarker Measures of Aging
FAS
|
2 Protein Expression (relative units)
Standard Deviation 562
|
-151 Protein Expression (relative units)
Standard Deviation 349
|
-43 Protein Expression (relative units)
Standard Deviation 577
|
792 Protein Expression (relative units)
Standard Deviation 3619
|
|
Mean Change in Blood-based Biomarker Measures of Aging
GDF-15
|
67 Protein Expression (relative units)
Standard Deviation 126
|
21 Protein Expression (relative units)
Standard Deviation 57
|
95 Protein Expression (relative units)
Standard Deviation 77
|
168 Protein Expression (relative units)
Standard Deviation 202
|
|
Mean Change in Blood-based Biomarker Measures of Aging
ICAM-1
|
1338 Protein Expression (relative units)
Standard Deviation 17293
|
-5364 Protein Expression (relative units)
Standard Deviation 16876
|
-1724 Protein Expression (relative units)
Standard Deviation 12356
|
1124 Protein Expression (relative units)
Standard Deviation 31718
|
|
Mean Change in Blood-based Biomarker Measures of Aging
INFg
|
-0.02 Protein Expression (relative units)
Standard Deviation 1.3
|
-0.16 Protein Expression (relative units)
Standard Deviation 0.61
|
0.03 Protein Expression (relative units)
Standard Deviation 1.44
|
-0.04 Protein Expression (relative units)
Standard Deviation 0.49
|
|
Mean Change in Blood-based Biomarker Measures of Aging
IL-15
|
0.01 Protein Expression (relative units)
Standard Deviation 0.92
|
-1.13 Protein Expression (relative units)
Standard Deviation 4.8
|
3.70 Protein Expression (relative units)
Standard Deviation 16.68
|
-14.9 Protein Expression (relative units)
Standard Deviation 51.38
|
|
Mean Change in Blood-based Biomarker Measures of Aging
IL-7
|
-0.31 Protein Expression (relative units)
Standard Deviation 6.24
|
-3.18 Protein Expression (relative units)
Standard Deviation 7.35
|
-1.34 Protein Expression (relative units)
Standard Deviation 7.19
|
1.34 Protein Expression (relative units)
Standard Deviation 9.91
|
|
Mean Change in Blood-based Biomarker Measures of Aging
IL-8
|
0.28 Protein Expression (relative units)
Standard Deviation 2.91
|
-0.58 Protein Expression (relative units)
Standard Deviation 2.94
|
0.33 Protein Expression (relative units)
Standard Deviation 2.59
|
1.07 Protein Expression (relative units)
Standard Deviation 2.09
|
|
Mean Change in Blood-based Biomarker Measures of Aging
MCP-1
|
6 Protein Expression (relative units)
Standard Deviation 54
|
11 Protein Expression (relative units)
Standard Deviation 32
|
-5 Protein Expression (relative units)
Standard Deviation 47
|
14 Protein Expression (relative units)
Standard Deviation 52
|
|
Mean Change in Blood-based Biomarker Measures of Aging
MDC
|
-11 Protein Expression (relative units)
Standard Deviation 67
|
-33 Protein Expression (relative units)
Standard Deviation 87
|
5 Protein Expression (relative units)
Standard Deviation 103
|
98 Protein Expression (relative units)
Standard Deviation 328
|
|
Mean Change in Blood-based Biomarker Measures of Aging
MMP-2
|
-569 Protein Expression (relative units)
Standard Deviation 23803
|
-5747 Protein Expression (relative units)
Standard Deviation 21459
|
-9175 Protein Expression (relative units)
Standard Deviation 19076
|
1578 Protein Expression (relative units)
Standard Deviation 29394
|
|
Mean Change in Blood-based Biomarker Measures of Aging
MMP-7
|
82 Protein Expression (relative units)
Standard Deviation 212
|
-96 Protein Expression (relative units)
Standard Deviation 477
|
135 Protein Expression (relative units)
Standard Deviation 191
|
279 Protein Expression (relative units)
Standard Deviation 370
|
|
Mean Change in Blood-based Biomarker Measures of Aging
MMP-9
|
3721 Protein Expression (relative units)
Standard Deviation 5553
|
-3602 Protein Expression (relative units)
Standard Deviation 61421
|
25103 Protein Expression (relative units)
Standard Deviation 60279
|
-10826 Protein Expression (relative units)
Standard Deviation 53765
|
|
Mean Change in Blood-based Biomarker Measures of Aging
Osteoactivin
|
-334 Protein Expression (relative units)
Standard Deviation 1184
|
-323 Protein Expression (relative units)
Standard Deviation 1169
|
-234 Protein Expression (relative units)
Standard Deviation 1295
|
-531 Protein Expression (relative units)
Standard Deviation 1869
|
|
Mean Change in Blood-based Biomarker Measures of Aging
Osteopontin
|
336 Protein Expression (relative units)
Standard Deviation 5519
|
374 Protein Expression (relative units)
Standard Deviation 5069
|
1369 Protein Expression (relative units)
Standard Deviation 3596
|
1955 Protein Expression (relative units)
Standard Deviation 10590
|
|
Mean Change in Blood-based Biomarker Measures of Aging
PARC
|
-491 Protein Expression (relative units)
Standard Deviation 6054
|
-4167 Protein Expression (relative units)
Standard Deviation 11225
|
1466 Protein Expression (relative units)
Standard Deviation 7506
|
1926 Protein Expression (relative units)
Standard Deviation 17278
|
|
Mean Change in Blood-based Biomarker Measures of Aging
PDGF-AA
|
-8587 Protein Expression (relative units)
Standard Deviation 26863
|
-8889 Protein Expression (relative units)
Standard Deviation 26841
|
3295 Protein Expression (relative units)
Standard Deviation 17592
|
9499 Protein Expression (relative units)
Standard Deviation 25431
|
|
Mean Change in Blood-based Biomarker Measures of Aging
PDGF-AB
|
28 Protein Expression (relative units)
Standard Deviation 116
|
-287 Protein Expression (relative units)
Standard Deviation 1172
|
117 Protein Expression (relative units)
Standard Deviation 1460
|
561 Protein Expression (relative units)
Standard Deviation 1415
|
|
Mean Change in Blood-based Biomarker Measures of Aging
PLA2G7
|
-2817 Protein Expression (relative units)
Standard Deviation 14312
|
-248 Protein Expression (relative units)
Standard Deviation 46249
|
17230 Protein Expression (relative units)
Standard Deviation 50079
|
-7747 Protein Expression (relative units)
Standard Deviation 31756
|
|
Mean Change in Blood-based Biomarker Measures of Aging
RAGE
|
-167 Protein Expression (relative units)
Standard Deviation 245
|
13 Protein Expression (relative units)
Standard Deviation 310
|
-125 Protein Expression (relative units)
Standard Deviation 156
|
-6 Protein Expression (relative units)
Standard Deviation 359
|
|
Mean Change in Blood-based Biomarker Measures of Aging
RANTES
|
-1395 Protein Expression (relative units)
Standard Deviation 16663
|
-358 Protein Expression (relative units)
Standard Deviation 23741
|
-1233 Protein Expression (relative units)
Standard Deviation 17146
|
5279 Protein Expression (relative units)
Standard Deviation 16267
|
|
Mean Change in Blood-based Biomarker Measures of Aging
SOST
|
18 Protein Expression (relative units)
Standard Deviation 71
|
6 Protein Expression (relative units)
Standard Deviation 47
|
16 Protein Expression (relative units)
Standard Deviation 50
|
9 Protein Expression (relative units)
Standard Deviation 69
|
|
Mean Change in Blood-based Biomarker Measures of Aging
SPARC
|
38039 Protein Expression (relative units)
Standard Deviation 316563
|
-122037 Protein Expression (relative units)
Standard Deviation 435422
|
-1425 Protein Expression (relative units)
Standard Deviation 22653
|
103686 Protein Expression (relative units)
Standard Deviation 410690
|
|
Mean Change in Blood-based Biomarker Measures of Aging
TNF RI
|
8 Protein Expression (relative units)
Standard Deviation 95
|
-18 Protein Expression (relative units)
Standard Deviation 133
|
40 Protein Expression (relative units)
Standard Deviation 114
|
27 Protein Expression (relative units)
Standard Deviation 132
|
|
Mean Change in Blood-based Biomarker Measures of Aging
TNF RII
|
-40 Protein Expression (relative units)
Standard Deviation 215
|
136 Protein Expression (relative units)
Standard Deviation 514
|
72 Protein Expression (relative units)
Standard Deviation 246
|
15 Protein Expression (relative units)
Standard Deviation 279
|
|
Mean Change in Blood-based Biomarker Measures of Aging
TNF-a
|
0.47 Protein Expression (relative units)
Standard Deviation 3.19
|
-0.03 Protein Expression (relative units)
Standard Deviation 2.35
|
-0.14 Protein Expression (relative units)
Standard Deviation 3.03
|
-0.65 Protein Expression (relative units)
Standard Deviation 8.08
|
|
Mean Change in Blood-based Biomarker Measures of Aging
uPAR
|
-20 Protein Expression (relative units)
Standard Deviation 57
|
-27 Protein Expression (relative units)
Standard Deviation 67
|
-16 Protein Expression (relative units)
Standard Deviation 52
|
11 Protein Expression (relative units)
Standard Deviation 74
|
|
Mean Change in Blood-based Biomarker Measures of Aging
VEGF
|
-14 Protein Expression (relative units)
Standard Deviation 26
|
-39 Protein Expression (relative units)
Standard Deviation 99
|
6 Protein Expression (relative units)
Standard Deviation 50
|
6 Protein Expression (relative units)
Standard Deviation 62
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Metformin
Serious events: 0 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=47 participants at risk
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate).
The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
Metformin
n=54 participants at risk
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.3%
2/47 • Number of events 2 • From enrollment until completion of the study, up to 16 weeks
|
11.1%
6/54 • Number of events 9 • From enrollment until completion of the study, up to 16 weeks
|
|
Gastrointestinal disorders
Constipation
|
2.1%
1/47 • Number of events 1 • From enrollment until completion of the study, up to 16 weeks
|
7.4%
4/54 • Number of events 5 • From enrollment until completion of the study, up to 16 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
17.0%
8/47 • Number of events 9 • From enrollment until completion of the study, up to 16 weeks
|
35.2%
19/54 • Number of events 34 • From enrollment until completion of the study, up to 16 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
2.1%
1/47 • Number of events 1 • From enrollment until completion of the study, up to 16 weeks
|
5.6%
3/54 • Number of events 3 • From enrollment until completion of the study, up to 16 weeks
|
|
Gastrointestinal disorders
Nausea
|
14.9%
7/47 • Number of events 7 • From enrollment until completion of the study, up to 16 weeks
|
18.5%
10/54 • Number of events 13 • From enrollment until completion of the study, up to 16 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
2.1%
1/47 • Number of events 1 • From enrollment until completion of the study, up to 16 weeks
|
9.3%
5/54 • Number of events 6 • From enrollment until completion of the study, up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
4.3%
2/47 • Number of events 2 • From enrollment until completion of the study, up to 16 weeks
|
5.6%
3/54 • Number of events 3 • From enrollment until completion of the study, up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle Cramps
|
0.00%
0/47 • From enrollment until completion of the study, up to 16 weeks
|
5.6%
3/54 • Number of events 3 • From enrollment until completion of the study, up to 16 weeks
|
|
Nervous system disorders
Dizziness
|
2.1%
1/47 • Number of events 1 • From enrollment until completion of the study, up to 16 weeks
|
11.1%
6/54 • Number of events 6 • From enrollment until completion of the study, up to 16 weeks
|
|
Nervous system disorders
Headache
|
2.1%
1/47 • Number of events 1 • From enrollment until completion of the study, up to 16 weeks
|
14.8%
8/54 • Number of events 9 • From enrollment until completion of the study, up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Vesicles
|
6.4%
3/47 • Number of events 3 • From enrollment until completion of the study, up to 16 weeks
|
5.6%
3/54 • Number of events 3 • From enrollment until completion of the study, up to 16 weeks
|
Additional Information
Benjamin Miller Professor, PI
Oklahoma Medical Research Foundation
Phone: 4052717767
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place