Trial Outcomes & Findings for Metformin for Preventing Frailty in High-risk Older Adults (NCT NCT02570672)

NCT ID: NCT02570672

Last Updated: 2025-08-06

Results Overview

Frailty index based on deficit accumulation. The frailty index will be measured based on the presence of several potential deficits, including chronic diseases, conditions, and impairments. Deficits are ascertained from study visit assessments, including medical history, physical examination, physical function, cognitive function, disability, and quality of life. The frailty index score was calculated as the ratio of the number of deficits to the total number of deficits. The total range of the index is 0 to 1, with higher score indicating more frailty. The outcome is the covariate adjusted monthly rate of change in the frailty index over the study period.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 141 participants
• Primary outcome timeframe: 2 years
• Results posted on: 2025-08-06

Participant Flow

Participant milestones

Measure	Metformin Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) Metformin: Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.	Placebo Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. Placebo: Subjects will randomized to placebo will receive placebo
Overall Study STARTED	70	71
Overall Study COMPLETED	58	67
Overall Study NOT COMPLETED	12	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Metformin for Preventing Frailty in High-risk Older Adults

Baseline characteristics by cohort

Measure	Metformin n=70 Participants Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) Metformin: Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.	Placebo n=71 Participants Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. Placebo: Subjects will randomized to placebo will receive placebo	Total n=141 Participants Total of all reporting groups
Age, Continuous	71.0 years STANDARD_DEVIATION 5.4 • n=93 Participants	72.6 years STANDARD_DEVIATION 5.1 • n=4 Participants	71.78 years STANDARD_DEVIATION 5.28 • n=27 Participants
Sex: Female, Male Female	34 Participants n=93 Participants	34 Participants n=4 Participants	68 Participants n=27 Participants
Sex: Female, Male Male	36 Participants n=93 Participants	37 Participants n=4 Participants	73 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=93 Participants	22 Participants n=4 Participants	49 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=93 Participants	49 Participants n=4 Participants	92 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized White	64 Participants n=93 Participants	68 Participants n=4 Participants	132 Participants n=27 Participants
Race/Ethnicity, Customized African American	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized Other	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants
Region of Enrollment United States	70 participants n=93 Participants	71 participants n=4 Participants	141 participants n=27 Participants

PRIMARY outcome

Timeframe: 2 years

Population: Participants that completed study

Frailty index based on deficit accumulation. The frailty index will be measured based on the presence of several potential deficits, including chronic diseases, conditions, and impairments. Deficits are ascertained from study visit assessments, including medical history, physical examination, physical function, cognitive function, disability, and quality of life. The frailty index score was calculated as the ratio of the number of deficits to the total number of deficits. The total range of the index is 0 to 1, with higher score indicating more frailty. The outcome is the covariate adjusted monthly rate of change in the frailty index over the study period.

Outcome measures

Measure	Metformin n=58 Participants Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) Metformin: Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.	Placebo n=67 Participants Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. Placebo: Subjects will randomized to placebo will receive placebo
Frailty Index Based on Deficit Accumulation	-0.0002 Index score Standard Error 0.0002	0.0002 Index score Standard Error 0.0002

PRIMARY outcome

Timeframe: Baseline to 2 years

Population: Participants that completed the study

The frailty score will be measured based on the following 5 frailty characteristics: 1) unintentional weight loss of >= 10 pounds in last year at baseline and ≥5% loss of body weight during follow-up; 2) self-reported exhaustion based on the Geriatric Depression Scale item, "Do you feel full of energy?;" 3) muscle weakness based on hand grip strength measurement (standardized cut points are published); 4) slow gait speed based on 10-foot walk (standardized cut points are published); and 5) low physical activity measured in kilocalories/week based on the Minnesota Leisure Time Questionnaire (standardized cut points are published). The Fried frailty score was calculated as the number of frailty characteristics present, each with a score of 0 or 1. The total range of scores is 0-5, with a higher score indicating more frailty. The outcome is the covariate adjusted monthly rate of change in the Fried frailty score over the study period.

Outcome measures

Measure	Metformin n=58 Participants Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) Metformin: Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.	Placebo n=67 Participants Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. Placebo: Subjects will randomized to placebo will receive placebo
Fried Frailty Phenotype Criteria	0.0289 Score on a scale Standard Error 0.0049	0.0164 Score on a scale Standard Error 0.0058

Adverse Events

Metformin

Serious events: 0 serious events

Other events: 70 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 71 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Metformin n=70 participants at risk Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) Metformin: Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.	Placebo n=71 participants at risk Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. Placebo: Subjects will randomized to placebo will receive placebo
Gastrointestinal disorders Diarrhea	71.4% 50/70 • Number of events 133 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	46.5% 33/71 • Number of events 75 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
Nervous system disorders Arthralgia	31.4% 22/70 • Number of events 33 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	33.8% 24/71 • Number of events 55 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
Gastrointestinal disorders Nausea	30.0% 21/70 • Number of events 31 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	16.9% 12/71 • Number of events 18 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
Gastrointestinal disorders Flatulence	21.4% 15/70 • Number of events 22 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	9.9% 7/71 • Number of events 11 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
Blood and lymphatic system disorders Peripheral edema	21.4% 15/70 • Number of events 21 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	18.3% 13/71 • Number of events 16 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
General disorders Pain in extremity	21.4% 15/70 • Number of events 19 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	21.1% 15/71 • Number of events 26 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
Blood and lymphatic system disorders Contusion	20.0% 14/70 • Number of events 21 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	23.9% 17/71 • Number of events 26 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.
Nervous system disorders Headache	20.0% 14/70 • Number of events 23 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.	14.1% 10/71 • Number of events 12 • Adverse events were collected from baseline to 2 years. All cause mortality and serious adverse events, related and unrelated to study intervention, are reported.

Additional Information

Sara Espinoza

UT Health San Antonio

Phone: 210 617 5197

Email: Sara.Espinoza@cshs.org

Results disclosure agreements

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