Trial Outcomes & Findings for Metformin and Muscle in Insulin-resistant Older Veterans (NCT NCT01804049)

NCT ID: NCT01804049

Last Updated: 2020-02-11

Results Overview

At baseline, 1, 2, and 3 year follow-up visits, participants will have whole body dual x-ray absorptiometry scans (DXA) with a Hologic QDR 4500W DXA scanner by a certified DXA operator to determine total body lean mass and appendicular lean mass (Kg). The changes in appendicular and total lean mass were calculated by determining the change from baseline to the three year data point. If participants withdrew from the study prior to collection of 3 year data, the final time point available was used.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 120 participants
• Primary outcome timeframe: 3 years
• Results posted on: 2020-02-11

Participant Flow

Participants were recruited via advertisement flyers, primary care referral and letters to subjects in the research data warehouse within the Portland VA Healthcare System between May 2014 and August 2015. The first participant was enrolled in the study on May 27,2014 and the last participant was enrolled on August 12, 2015.

Of the 431 assessed for eligibility, 120 met inclusion criteria and were randomized to treatment.

Participant milestones

Measure	Placebo 60 participants will be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.	Metformin 60 enrolled participants will be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.
Overall Study STARTED	43	77
Overall Study COMPLETED	32	45
Overall Study NOT COMPLETED	11	32

Reasons for withdrawal

Measure	Placebo 60 participants will be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.	Metformin 60 enrolled participants will be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.
Overall Study Adverse Event	2	10
Overall Study Lost to Follow-up	2	1
Overall Study Decreased interest/personal	4	5
Overall Study Other health concerns	2	7
Overall Study Moved out of area	0	7
Overall Study other MD recommended	1	1
Overall Study Enrollment in dual studies	0	1

Baseline Characteristics

Metformin and Muscle in Insulin-resistant Older Veterans

Baseline characteristics by cohort

Measure	Placebo n=43 Participants 60 participants will be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.	Metformin n=77 Participants 60 enrolled participants will be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.	Total n=120 Participants Total of all reporting groups
Age, Continuous	71.4 years STANDARD_DEVIATION 6.5 • n=5 Participants	71.2 years STANDARD_DEVIATION 5.1 • n=7 Participants	71.3 years STANDARD_DEVIATION 5.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	76 Participants n=7 Participants	115 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	71 Participants n=7 Participants	113 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	3 Participants n=7 Participants	3 Participants n=5 Participants
BMI	29.527 kg/m2 STANDARD_DEVIATION 4.177 • n=5 Participants	29.246 kg/m2 STANDARD_DEVIATION 4.860 • n=7 Participants	29.347 kg/m2 STANDARD_DEVIATION 4.610 • n=5 Participants
Dual-energy X-ray absorptiometry (DEXA) Total Lean Mass (g)	58902.9 grams STANDARD_DEVIATION 7882.7 • n=5 Participants	59412.4 grams STANDARD_DEVIATION 7366.0 • n=7 Participants	59227.8 grams STANDARD_DEVIATION 7526.4 • n=5 Participants
DEXA Appendicular Lean Mass (g)	24676.7 grams STANDARD_DEVIATION 3913.7 • n=5 Participants	24923.5 grams STANDARD_DEVIATION 3599.3 • n=7 Participants	24834.0 grams STANDARD_DEVIATION 3700.7 • n=5 Participants
400 Meter Walk Time (seconds)	292.9 seconds STANDARD_DEVIATION 50.2 • n=5 Participants	297.3 seconds STANDARD_DEVIATION 48.8 • n=7 Participants	295.7 seconds STANDARD_DEVIATION 49.1 • n=5 Participants

PRIMARY outcome

Timeframe: 3 years

Population: A simple adaptive randomization scheme was developed to balance gender, age and BMI. 120 subjects were randomized to treatment conditions according to 64% to 36% allocation probabilities. Subjects were followed for up to 3 years, with walk time and lean mass measured annually. The study experienced roughly 38% loss-to-follow up at year 3.

At baseline, 1, 2, and 3 year follow-up visits, participants will have whole body dual x-ray absorptiometry scans (DXA) with a Hologic QDR 4500W DXA scanner by a certified DXA operator to determine total body lean mass and appendicular lean mass (Kg). The changes in appendicular and total lean mass were calculated by determining the change from baseline to the three year data point. If participants withdrew from the study prior to collection of 3 year data, the final time point available was used.

Outcome measures

Measure	Placebo n=43 Participants 60 participants will be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.	Metformin n=77 Participants 60 enrolled participants will be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.
Change in Total Lean Mass From Baseline Total Lean Mass Decrease from Baseline	392.4 grams lean mass Standard Deviation 2583.8	548.0 grams lean mass Standard Deviation 2339.4
Change in Total Lean Mass From Baseline Appendicular Lean Mass Decrease from Baseline	322.8 grams lean mass Standard Deviation 1342.3	697.6 grams lean mass Standard Deviation 2318.8

SECONDARY outcome

Timeframe: 3 years

At baseline, 1, 2, and 3 year follow-up visits, participants will have physical performance assessed using a 400 meter timed walk. We report the 400 meter timed walk speed as the change from baseline in seconds. The change in walk speed from baseline to the three year time point was used for analysis. For participants who withdrew from the study early, the walk speed from the final data point collected was used.

Outcome measures

Measure	Placebo n=43 Participants 60 participants will be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.	Metformin n=77 Participants 60 enrolled participants will be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.
Change in Physical Performance - 400 Meter Walk Speed	-2.82 seconds Standard Deviation 51.35	0.46 seconds Standard Deviation 29.98

SECONDARY outcome

Timeframe: 6 months

Population: Due to loss of sample and unmatched (time 0 and 6 month) sample availability as well as poor sample integrity, no interpretable histology data is available. No histology data was collected/analyzed from any samples for this Outcome measure.

At baseline and 6 month follow-up visits, 32 subjects will undergo a muscle biopsy of the vastus lateralis muscle 15 cm above the patella using the modified Bergstrom technique under local anesthesia. The muscle biopsy specimens will be used for the histochemical and transcriptome analyses

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 25 serious events

Other events: 24 other events

Deaths: 0 deaths

Metformin

Serious events: 52 serious events

Other events: 52 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=43 participants at risk 60 participants were to be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study. 43 participants were allocated to the placebo group.	Metformin n=77 participants at risk 60 enrolled participants were to be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study. 77 participants were allocated to the metformin group.
Gastrointestinal disorders small bowel obstruction	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders pancreatitis	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Nervous system disorders stroke/TIA	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	2.6% 2/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures prostatectomy	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	6.5% 5/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Infections and infestations abscess	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Cardiac disorders atrial fibrillation	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Infections and infestations appendicitis	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders rectal bleeding	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Nervous system disorders syncope	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	2.6% 2/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Renal and urinary disorders acute kidney injury	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Cardiac disorders myocardial infarction	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	2.6% 2/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Cardiac disorders chest pain	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	5.2% 4/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Nervous system disorders altered mental status	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Respiratory, thoracic and mediastinal disorders upper respiratory infection	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	3.9% 3/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders acute cholecystitis	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures elective craniotomy	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures transsphenoidal pituitary surgery	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures hip replacement	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Blood and lymphatic system disorders leukemia	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Blood and lymphatic system disorders severe anemia	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Injury, poisoning and procedural complications large hematoma	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders severe diarrhea	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	2.6% 2/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders paraesophageal hernia	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) benign brain tumor	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures knee replacement	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures laminectomy	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures repair of esophageal tear	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Injury, poisoning and procedural complications fall requiring hospitalization	11.6% 5/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	3.9% 3/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Injury, poisoning and procedural complications head injury	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures bladder surgery	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Eye disorders eye infection	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Musculoskeletal and connective tissue disorders hip pain	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Injury, poisoning and procedural complications medication interaction	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) kidney or bladder cancer	4.7% 2/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders abdominal pain intractable	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) melanoma	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Endocrine disorders new onset overt diabetes	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Eye disorders detached retina	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures cardioversion	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Injury, poisoning and procedural complications trauma	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Infections and infestations gastrointestinal infection	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	2.6% 2/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Musculoskeletal and connective tissue disorders ankle fracture	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Cardiac disorders hypotension	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Surgical and medical procedures pacemaker placement	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	0.00% 0/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Respiratory, thoracic and mediastinal disorders pneumonia	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	1.3% 1/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.

Other adverse events

Measure	Placebo n=43 participants at risk 60 participants were to be randomized to placebo pills. placebo: One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study. 43 participants were allocated to the placebo group.	Metformin n=77 participants at risk 60 enrolled participants were to be randomized to metformin. metformin: Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study. 77 participants were allocated to the metformin group.
Musculoskeletal and connective tissue disorders fall	30.2% 13/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	23.4% 18/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Endocrine disorders elevated glucose	16.3% 7/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	7.8% 6/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders nausea	2.3% 1/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	9.1% 7/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Gastrointestinal disorders diarrhea	4.7% 2/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	33.8% 26/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Nervous system disorders fatigue	9.3% 4/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	10.4% 8/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
Nervous system disorders decreased memory	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	5.2% 4/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.
General disorders weight loss	0.00% 0/43 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.	11.7% 9/77 • Adverse event data were collected over a three year period. At each study visit, participants were queried regarding adverse events. In between visits, participants could contact study staff to notify staff of adverse events. Laboratory tests were collected at participant visits and were evaluated for adverse events by study staff.

Additional Information

Dr Robert Klein

VAORD - Portland VA Health Care System

Phone: 503-220-8268

Email: kleinro@ohsu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place