This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effect of Metformin on Frailty in 12 Subjects (NCT03451006), a randomized phase 2 study. The primary outcome is Change in Frailty.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03451006 |
| Phase | Phase 2 |
| Condition | Aging, Inflammation, Frailty |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned older people in a study of aging, inflammation and frailty. The registry record lists enrollment of 7. It does not report further eligibility details or a fuller description of the enrolled participants.
Intervention
The intervention was metformin, described as a 500mg tablet taken by mouth every 6 to 8 hours for one year.
Comparator
The comparator was placebo taken by mouth every 6 to 8 hours for one year. The registry record identifies the trial as randomized, double-masked and parallel-group.
Primary question
The primary question was whether frailty changed from baseline to 12 months, measured with the Short Physical Performance Battery (SPPB). The registry record says the study was terminated because recruitment was difficult and the target was not achieved; data were not collected or analyzed.
The study’s stated rationale linked metformin to aging-related biochemical parameters and physical performance. Its brief summary describes an interest in whether chronic metformin administration could improve cellular processes and physical performance. The primary outcome, however, was a measure of physical performance used to assess frailty, rather than a direct measure of longevity or cellular machinery. The registry lists changes in several biomarkers as secondary outcomes, including Interleukin 6, Matrix Metalloproteinase, Plasminogen Activator Inhibitor, Monocyte Chemotactic Protein-1 and Activin.
Because no outcome data were collected or analyzed, the registry record cannot answer whether SPPB scores changed, whether the arms differed, or whether any of the listed biomarkers changed. The clinical question remains unanswered by this trial record.
3. Trial Design
The registry describes the study as a Phase 2 randomized, double-masked, parallel-group trial comparing metformin with placebo. Mayo Clinic is listed as the sponsor. The stated enrollment was 7. The intervention description specifies metformin 500mg by mouth every 6 to 8 hours for one year; the placebo was also taken by mouth every 6 to 8 hours for one year.
The registry lists the study start as 2018-05-24 and primary completion as 2021-12-16. Its current status is terminated. The primary outcome timeframe was baseline and 12 months. The record’s explanation for termination is that recruitment was difficult and was not achieved. It explicitly states that data were not collected nor analyzed.
The registry includes safety group counts of 4 for Metformin and 3 for Placebo. Those counts do not supply outcome measurements or establish how many participants completed the intended year of treatment. The record does not report completion, adherence, treatment exposure, or withdrawals by arm. It also does not provide details about the randomization sequence, allocation concealment, masking procedures, or the intended target enrollment.
The study was described as a pilot and feasibility study in its official title. That framing is relevant: the registry’s stated reason for termination concerns recruitment feasibility, and the absence of collected outcome data means the record offers no estimate of treatment effect. No protocol details beyond those recorded in the registry should be inferred.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Metformin | Placebo |
|---|---|---|
| STARTED | 4 | 3 |
| COMPLETED | 2 | 1 |
| NOT COMPLETED | 2 | 2 |
Reasons for not completing this period:
| Reason | Metformin | Placebo |
|---|---|---|
| Withdrawal by Subject | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Metformin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 3 | 7 | |
| Age, Continuous | years | 75.75 (64.0 to 86.0) | 77.33 (71.0 to 81.0) | 76.54 (64.0 to 86.0) |
| Sex: Female, Male: Female | Participants | 2 | 1 | 3 |
| Sex: Female, Male: Male | Participants | 2 | 2 | 4 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 4 | 3 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Frailty, measured over Baseline, 12 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in frailty, measured by the Short Physical Performance Battery (SPPB), with assessments specified at baseline and 12 months. The SPPB combines results from gait speed, chair stand and balance tests. The registry describes it as a tool used to predict possible disability and to monitor function in older people.
SPPB scores range from 0 (worst performance) to 12 (best performance). The registry defines frailty as a score <9. These details explain how the endpoint was intended to represent physical function and frailty: a composite score draws on more than one performance task, while the stated threshold gives a criterion for classifying frailty.
The endpoint’s clinical meaning depends on observed measurements and their comparison over the specified timeframe. The registry record says no data were collected or analyzed, so it reports no baseline scores, 12-month scores, changes, or comparisons between the metformin and placebo groups. It is therefore not possible to describe the direction, size, or precision of any change in SPPB or frailty status from this trial.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the trial was terminated because recruitment was difficult and was not achieved. The registry says data were not collected nor analyzed. Consequently, there is no reported primary outcome estimate, no comparison of SPPB change between groups, and no treatment-effect confidence interval or p-value to interpret. The record does not establish whether metformin and placebo differed on frailty, or whether either group changed over time.
The enrollment listed is 7, and the registry’s safety groups list 4 participants at risk in the Metformin group and 3 in the Placebo group. These counts describe the recorded groups for safety reporting; they do not replace the missing outcome observations. In particular, group counts alone cannot show baseline comparability, follow-up completion, treatment exposure, or changes in SPPB. The registry does not report those details.
The registry lists 11 outcome measures and zero analyses. It also names five secondary biomarker outcomes: changes in Interleukin 6, Matrix Metalloproteinase, Plasminogen Activator Inhibitor, Monocyte Chemotactic Protein-1 and Activin. Since the record says data were not collected or analyzed, none of these listed outcomes can be interpreted as an observed response. Listing an outcome indicates that it was planned or registered, not that a value was obtained.
A planned randomized, double-masked comparison could in principle support an estimate of differences between assigned groups. But design labels alone do not produce evidence about an outcome. Here the absence of collected and analyzed data prevents estimation of the size or direction of a difference, and leaves its precision unknown. There is no basis in the registry record for claims about benefit, lack of benefit, or equivalence.
The termination also changes what can be learned from this trial. The record documents a recruitment challenge, which is relevant to feasibility; it does not provide enough detail to identify why recruitment was difficult or what recruitment changes might have addressed it. The study therefore offers a record of a feasibility problem, not a completed assessment of frailty or biomarkers. Any sample-size planning illustration associated with the posted results should be understood as hypothetical planning, not as observed power or evidence about the trial’s effect. No sponsor analysis is reported that could take precedence over a recalculation.
9. Statistical Methods Explained
The statistical interpretation is constrained by the registry’s explicit statement that data were not collected nor analyzed. Statistical methods can describe what an analysis would seek to estimate, but they cannot recover unobserved SPPB or biomarker values. The record reports zero analyses, and it contains no outcome summary statistics, effect estimates, uncertainty intervals, or hypothesis-test results. Thus there is no statistical result from the trial to evaluate for magnitude, precision, or compatibility with different effects.
What would a between-group comparison estimate?
In a randomized parallel-group trial, a treatment comparison would ordinarily summarize the outcome in each assigned group and estimate a contrast between them. For this study, the primary outcome was change in SPPB from baseline to 12 months. A contrast in changes would address whether the groups had different average changes over that interval, subject to the analysis plan and available measurements. The registry record does not report an analysis plan or any observed endpoint values, so no such contrast can be stated.
Randomization is intended to make assigned groups comparable on average, but it does not guarantee identical groups, particularly when enrollment is small. Baseline data would help describe the actual groups, and follow-up data would be needed to estimate change. Neither is reported for the primary endpoint. The group counts in the safety record do not provide these missing outcome distributions.
What would a confidence interval contribute?
General statistical explanation: a confidence interval expresses the uncertainty around an estimated quantity under a specified analysis and its assumptions. It helps distinguish a relatively precise estimate from one compatible with a broad range of effects. An interval is not reported for this trial’s primary outcome because there is no analyzed estimate in the registry record. Without an estimate and its uncertainty, the posted information cannot indicate how precisely a treatment contrast was measured.
A p-value, if reported, would address how compatible the observed data are with a specified null hypothesis under the test’s assumptions. It would not by itself describe the size or importance of an effect. No p-value is reported, and the absence of one must not be interpreted as evidence that there was no effect: the record says the data were not collected or analyzed.
How should the listed outcomes be understood?
The SPPB was the primary measure, with its stated range and frailty threshold. The registry also lists changes in biochemical measures as secondary outcomes. These are distinct endpoints and would require their own observed values and analysis choices. A list of outcomes is not a set of results. The record’s count of 11 outcome measures does not mean that 11 outcomes were analyzed; it reports zero analyses.
General statistical explanation: measurements collected at multiple time points or across multiple outcomes raise questions about which comparisons are primary and how to interpret chance findings across many tests. A prespecified hierarchy or multiplicity adjustment can help address that issue. The registry record does not report such a plan, and there are no analyzed results to assess for multiplicity.
What does a planning illustration mean?
General statistical explanation: sample-size planning can illustrate how many participants per arm might be needed under chosen assumptions about an effect, variability, significance level and allocation. Such an illustration is not a result of the trial and is not observed power. The record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of an observed effect. These are assumptions for an illustration, not evidence that the trial used those methods in its own design. The registry does not report a sample-size justification for the trial.
The record does not state an observed effect, and no outcome data were analyzed. Any planning calculation based on an observed effect therefore cannot be treated as an empirical estimate from these participants. The record’s instruction that time-to-event planning concerns total events does not change the interpretation of this primary SPPB outcome, which is not described as a time-to-event endpoint.
Why can no treatment conclusion be drawn?
An effect estimate requires measured outcomes and a defined comparison. Precision requires information about the observed variation and the analysis. Neither is available in the registry record. The study’s randomized and masked design labels describe intended structure, but they cannot substitute for outcome data. The statistically defensible reading is that the registered question was not answered in the reported record, while the recruitment difficulty is documented as a feasibility issue.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures, including the primary SPPB measure and secondary biomarker changes. It reports zero analyses and states that data were not collected nor analyzed. Accordingly, there are no reported outcome estimates whose interpretation could be affected by multiple testing, and no missing-outcome analysis can be assessed.
General statistical explanation: when a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiplicity. Researchers may prioritize a primary outcome, define a hierarchy, or use an adjustment. The registry record does not report how multiplicity was to be handled, so no such method should be attributed to this trial.
Missing data methods address outcomes that were not observed for some participants, but this record describes a more fundamental absence: data were not collected or analyzed. It does not report partial outcome collection, reasons for individual missing measurements, imputation, sensitivity analyses, or follow-up status. The extent and pattern of missingness beyond the stated lack of collected data are not reported in the registry record.
The analysis population is also not described. The record does not say whether an intention-to-treat, per-protocol, or other population was planned. It would be inappropriate to infer one from the randomized design. With no outcome data and no reported analysis population, there is no basis for reconstructing an analysis or evaluating how exclusions might affect results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Metformin | 0 | 4 | 0.0% |
| Placebo | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Metformin | 0 of 4 |
| Placebo | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Metformin | 0 of 4 |
| Placebo | 0 of 3 |
The registry’s safety record lists 4 participants at risk in the Metformin group and 3 in the Placebo group. For each group, it records 0 serious adverse events, 0 other adverse events and 0 deaths. No serious adverse event terms are listed.
These are counts in the registry’s safety record, not evidence that the treatments have no risks. The group sizes are small, and the record states that data were not collected nor analyzed for the study. The safety figures should therefore be read narrowly as the reported event counts, not as a precise estimate of event rates or a reliable comparison between groups.
The registry record does not report the method or observation period used for safety ascertainment, the extent of treatment exposure, or details of systematic adverse-event collection. It also does not provide additional safety analyses. Zero recorded events cannot establish that no events occurred outside what was captured in this record, nor can it establish comparative safety.
12. What the Result Does, and Does Not, Mean
This trial record describes a randomized, double-masked, parallel-group Phase 2 study of metformin and placebo, with change in SPPB-defined frailty as the primary outcome. Its most informative result is about feasibility: recruitment was difficult and was not achieved, and the study was terminated. The registry explicitly states that data were not collected nor analyzed.
That means the posted record does not provide evidence for or against a difference in frailty between the groups. It reports no observed SPPB changes, biomarker results, estimates of treatment effect, confidence intervals or p-values. It cannot establish whether the intervention changed physical performance or aging-related biochemical measures. Nor does the absence of analyses show that the groups were equivalent or that an effect was absent.
The record also cannot show how well participants adhered to the intended regimen, how many completed one year, or how outcomes would have varied among those enrolled. These details are not reported in the registry record. The listed safety counts are limited descriptive counts and should not be taken as a comprehensive comparison of harms.
General statistical explanation: a small or incomplete study may be unable to estimate an effect precisely, but the central issue in this record is that outcome data were not collected and analyzed. It is not possible to characterize the uncertainty of an unreported effect estimate. Sample-size planning illustrations, if considered alongside the posted results, are hypothetical calculations under stated assumptions rather than evidence of the trial’s observed performance.
The appropriate conclusion is therefore limited: the trial did not answer its registered clinical question in the record, while documenting recruitment as a challenge. Any conclusion about metformin’s impact on frailty or biomarkers would go beyond the reported data.
13. Why This Trial Matters Statistically
This study matters statistically because it illustrates the distinction between a registered comparison and an answered research question. Randomization, masking and a defined primary outcome are design features, but evidence about an outcome still depends on collecting and analyzing measurements. The record reports that this did not happen.
The feasibility issue is itself relevant. Recruitment was difficult and was not achieved, and the study was terminated. That information can inform how readers interpret the absence of an efficacy estimate: the record is not a completed comparison with an inconclusive numerical result, but a trial that did not generate analyzed outcome data. The registry does not explain the specific causes of recruitment difficulty.
The primary endpoint also illustrates how a clinical concept is operationalized for analysis. Frailty was to be measured with the SPPB, a composite of gait speed, chair stand and balance tests, with a stated score range and threshold. Defining the measure and timeframe is necessary for reproducible analysis, but it does not reveal what participants scored or how scores changed.
Finally, the listing of multiple secondary outcomes raises general questions about multiplicity and analysis planning, while the absence of reported analyses leaves those questions unresolved for this trial. The record does not report how the outcomes would have been prioritized or tested. Statistical interpretation must distinguish these unknowns from findings: unreported methods and uncollected data do not support assumptions about the planned analysis or any treatment effect.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several limitations specific to this trial follow directly from the registry record. The study was terminated because recruitment was difficult and was not achieved. Although enrollment is listed as 7, the record says data were not collected nor analyzed. Consequently, neither the primary endpoint nor the secondary outcomes have reported results.
The registry does not report a target enrollment, a sample-size justification, or the reasons recruitment proved difficult. It also does not describe participant characteristics, eligibility criteria in detail, recruitment procedures, or the number who completed the intended one-year regimen. The safety group counts alone cannot answer these questions.
For the planned SPPB assessment, there are no reported baseline or 12-month values, no change estimates and no between-group comparison. The registry does not report an analysis population, missing-data approach, multiplicity strategy, or statistical analysis plan. The listed biomarker outcomes similarly have no reported measurements or analyses. These omissions preclude assessment of effect size, precision, baseline balance, adherence, and outcome completeness.
The record gives the planned treatment schedules and identifies the study as randomized and double-masked, but does not report operational details such as the randomization procedure or how masking was maintained. These details are not reported in the registry record. They should not be inferred from the design labels.
Finally, the safety counts are descriptive and limited. The registry does not report ascertainment procedures, exposure duration, or broader safety analyses. They should not be generalized into a conclusion about comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Metformin on Frailty in 12 Subjects — NCT03451006.
- Registry record last updated 2022-11-17; status last verified 2022-10.
- Results first posted 2022-11-17.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a Phase 2 randomized, double-masked, parallel-group pilot and feasibility study sponsored by Mayo Clinic. It compared metformin 500mg by mouth every 6 to 8 hours for one year with placebo on the same schedule. The primary outcome was change in SPPB-measured frailty from baseline to 12 months.
The study started on 2018-05-24, had a primary completion date of 2021-12-16, and is listed as terminated. Enrollment was 7. The registry says recruitment was difficult and was not achieved, and that data were not collected nor analyzed. It lists 11 outcome measures and zero analyses.
The safety record lists 4 participants at risk in the Metformin group and 3 in the Placebo group, with 0 serious adverse events, 0 other adverse events and 0 deaths in each. These counts do not provide a treatment-effect estimate. The clinical question about frailty and the listed biomarker outcomes remains unanswered by the reported record.