Trial Outcomes & Findings for Metformin in Longevity Study (MILES). (NCT NCT02432287)
NCT ID: NCT02432287
Last Updated: 2021-05-21
Results Overview
The investigators hypothesize that treatment with metformin will result in changes in the transcriptome. The investigators will test this by identifying increases in gene expression in muscle and adipose tissue with RNA Sequencing (RNA-Seq) in metformin and in placebo.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
16 participants
Primary outcome timeframe
6 weeks
Results posted on
2021-05-21
Participant Flow
Participant milestones
| Measure |
Metformin First, Then Placebo
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism.
Participants in the metformin first group took 1-2 metformin capsules 2 times daily for 6 weeks, followed by a 2 week washout period, concluding with 6 weeks of 1-2 placebo capsules (which matched metformin capsules) 2 x daily.
|
Placebo First, Then Metformin
Participants in the placebo first group took 1-2 placebo capsules 2 x daily (which matched metformin capsules) for 6 weeks, followed by a 2 week washout period, concluding with 6 weeks of 1-2 metformin capsules 2x daily.
|
|---|---|---|
|
First Intervention
STARTED
|
8
|
8
|
|
First Intervention
COMPLETED
|
8
|
7
|
|
First Intervention
NOT COMPLETED
|
0
|
1
|
|
Washout Period
STARTED
|
7
|
7
|
|
Washout Period
COMPLETED
|
7
|
7
|
|
Washout Period
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
7
|
7
|
|
Second Intervention
COMPLETED
|
7
|
7
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Metformin in Longevity Study (MILES).
Baseline characteristics by cohort
| Measure |
Metformin FIRST, Then Placebo
n=8 Participants
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism.
In the metformin first group, individuals took 1700mg/day metformin in 2 doses for 6 weeks, followed by 2 weeks of washout, and concluding with placebo capsules that matched the metformin for 6 weeks.
|
Placebo FIRST, Then Metformin
n=8 Participants
In the placebo first group, individuals took placebo capsules that matched metformin for 6 weeks, followed by 2 weeks of washout, and concluding with metformin 1700mg/day (in 2 doses) for 6 weeks.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69 years
STANDARD_DEVIATION 6.7 • n=5 Participants
|
74 years
STANDARD_DEVIATION 5.4 • n=7 Participants
|
71 years
STANDARD_DEVIATION 6.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
BMI
|
28 kg/m^2
STANDARD_DEVIATION 3.1 • n=5 Participants
|
32 kg/m^2
STANDARD_DEVIATION 4.4 • n=7 Participants
|
30 kg/m^2
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
Weight
|
84 kg
STANDARD_DEVIATION 14 • n=5 Participants
|
89 kg
STANDARD_DEVIATION 17 • n=7 Participants
|
87 kg
STANDARD_DEVIATION 16 • n=5 Participants
|
|
Fasting glucose
|
108 mg/dL
STANDARD_DEVIATION 13 • n=5 Participants
|
102 mg/dL
STANDARD_DEVIATION 10 • n=7 Participants
|
105 mg/dL
STANDARD_DEVIATION 12 • n=5 Participants
|
|
2-hour glucose
|
153 mg/dL
STANDARD_DEVIATION 13 • n=5 Participants
|
171 mg/dL
STANDARD_DEVIATION 24 • n=7 Participants
|
162 mg/dL
STANDARD_DEVIATION 21 • n=5 Participants
|
|
Antihypertensive therapy
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Statin therapy
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Aspirin therapy
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 weeksThe investigators hypothesize that treatment with metformin will result in changes in the transcriptome. The investigators will test this by identifying increases in gene expression in muscle and adipose tissue with RNA Sequencing (RNA-Seq) in metformin and in placebo.
Outcome measures
| Measure |
Metformin Treatment
n=14 Participants
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism.
Participants took metformin (1700 mg/day) for 6 weeks, followed by a 2 week washout, concluding with placebo pills (that matched metformin) for 6 weeks.
|
Placebo Treatment
n=14 Participants
Participants took placebo that matched metformin for 6 weeks.
|
|---|---|---|
|
Increase in Number of Expressed Genes in Muscle and Adipose Tissue Using RNA Sequencing (RNA-Seq)
genes increased in muscle
|
245 genes
|
402 genes
|
|
Increase in Number of Expressed Genes in Muscle and Adipose Tissue Using RNA Sequencing (RNA-Seq)
genes increased in adipose
|
15 genes
|
132 genes
|
SECONDARY outcome
Timeframe: 6 weeksAssessment of insulin sensitivity and insulin secretion. Insulin sensitivity will be estimated from insulin and glucose levels obtained following the standard meal challenge, using a modification of the Matsuda index, which has been widely used for non-invasive assessment of insulin sensitivity and shows good correlation (r=0.73) with results obtained from euglycemic hyperinsulinemic clamp studies. A higher Matsuda index indicates better insulin sensitivity. The insulin sensitivity index (ISI (comp) was calculated using the following equation (where g denotes glucose at various time points and i denotes insulin at various time points): ISI (comp)= 10000/ ((g0\*i0\* ((g0\*15+ g30\*30+ g60\*30+ g90\*30+ g120\*30+ g180\*30+ g240\*15)/240))\* ((i0\*15+ i30\*30+ i60\*30+ i90\*30\*+ i120\*30+ i180\*30+ i240\*15)/240))\^0.5
Outcome measures
| Measure |
Metformin Treatment
n=14 Participants
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism.
Participants took metformin (1700 mg/day) for 6 weeks, followed by a 2 week washout, concluding with placebo pills (that matched metformin) for 6 weeks.
|
Placebo Treatment
n=14 Participants
Participants took placebo that matched metformin for 6 weeks.
|
|---|---|---|
|
Mixed Meal Tolerance. Assessment of Insulin Sensitivity and Insulin Secretion (Using a Modification of the Matsuda Index)
|
5.6 index
Standard Deviation 3.9
|
4.1 index
Standard Deviation 2.1
|
Adverse Events
Metformin
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Metformin
n=15 participants at risk
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism.
Participants took metformin capsules 2 times daily for 6 weeks.
|
Placebo
n=15 participants at risk
All participants took placebo capsules 2 x daily for 6 weeks.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Hematoma
|
6.7%
1/15 • Number of events 1 • Adverse event data were collected during the study period of 14 weeks.
|
0.00%
0/15 • Adverse event data were collected during the study period of 14 weeks.
|
|
Gastrointestinal disorders
Nausea and vomiting
|
6.7%
1/15 • Number of events 1 • Adverse event data were collected during the study period of 14 weeks.
|
0.00%
0/15 • Adverse event data were collected during the study period of 14 weeks.
|
|
Renal and urinary disorders
urinary retention
|
6.7%
1/15 • Number of events 1 • Adverse event data were collected during the study period of 14 weeks.
|
0.00%
0/15 • Adverse event data were collected during the study period of 14 weeks.
|
Other adverse events
| Measure |
Metformin
n=15 participants at risk
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism.
Participants took metformin capsules 2 times daily for 6 weeks.
|
Placebo
n=15 participants at risk
All participants took placebo capsules 2 x daily for 6 weeks.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Shingles
|
0.00%
0/15 • Adverse event data were collected during the study period of 14 weeks.
|
6.7%
1/15 • Number of events 1 • Adverse event data were collected during the study period of 14 weeks.
|
|
Cardiac disorders
Chest pain
|
0.00%
0/15 • Adverse event data were collected during the study period of 14 weeks.
|
6.7%
1/15 • Number of events 1 • Adverse event data were collected during the study period of 14 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place