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 Pioglitazone on TIMP-3 and TACE in Type 2 Diabetes (NCT01223196), a randomized phase 4 study. The primary outcome is Whole Body Insulin Sensitivity During the Euglycemic Insulin Clamp.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01223196 |
| Phase | Phase 4 |
| Condition | Type 2 Diabetes |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The University of Texas Health Science Center at San Antonio |
| Results posted | Yes |
2. Clinical Question
Population
Adults with type 2 diabetes were the population of interest. The registry record lists an enrollment of 60, while the study summary describes thirty subjects participating in the study procedures. The record does not explain the difference between those figures or give further eligibility details, so the enrolled population cannot be characterized more specifically from the registry record.
Intervention
One arm was assigned pioglitazone, described as 15mg once a day for 6 months. The study examined insulin sensitivity and proposed investigating TIMP-3 and TACE, along with related measures in skeletal muscle and other tissues. The registry lists TACE activity in skeletal muscle as a secondary outcome.
Comparator
The comparison arm was assigned placebo once a day for 6 months. The record describes random allocation and double masking, with a parallel-group design. It does not report further details about how masking was maintained or how treatment assignments were generated.
Primary question
The primary question was whether whole-body insulin sensitivity, measured by the euglycemic insulin clamp, differed in relation to pioglitazone versus placebo treatment over the stated 6-month timeframe. The outcome is expressed as M/I: whole-body glucose uptake during the clamp, M, relative to circulating insulin levels during the clamp, I. The registry record does not report the arm-level primary-outcome results or a treatment-effect estimate, so the direction and precision of any observed difference cannot be assessed from this record.
3. Trial Design
The registry record describes a randomized, double-masked, parallel-group phase 4 trial comparing pioglitazone with placebo in people with type 2 diabetes. Enrollment is listed as 60. The record gives the start as 2009-08, primary completion as 2011-12, and study status as completed. These dates describe the study record, but do not provide details about the timing of individual participants’ assessments.
The pioglitazone arm is described as receiving 15mg once daily for 6 months; the placebo arm is described as receiving placebo once daily for 6 months. The primary outcome timeframe is also listed as 6 months. The summary says participants would undergo an oral glucose tolerance test, dual energy absorptiometry, and skeletal muscle biopsy, and describes a 24-week treatment period. The arm descriptions instead state 6 months. The registry record does not explain the wording difference between 24 weeks and 6 months.
The summary describes thirty subjects, whereas the enrollment field lists 60. The record does not explain how those figures relate, such as whether they refer to different stages or populations. It also does not report a detailed allocation procedure, masking procedures, eligibility criteria, or a statistical analysis plan. Randomization and double masking identify broad design features, but do not establish the exact implementation or analysis methods.
The stated scientific motivation concerns TIMP-3 and TACE, with the investigators proposing that they may relate to pioglitazone-associated changes in insulin sensitivity and endothelial function. The primary outcome recorded is insulin sensitivity measured by the euglycemic clamp. TACE activity in skeletal muscle is listed among secondary outcomes. The registry lists three outcome measures and five analyses, but does not provide the full definitions or results for all of them in the record.
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.
Before assignment: 36 patients did not meet the eligibility criteria and were excluded.
Overall Study
| Stage | Placebo | Pioglitazone |
|---|---|---|
| STARTED | 13 | 11 |
| COMPLETED | 9 | 11 |
| NOT COMPLETED | 4 | 0 |
Reasons for not completing this period:
| Reason | Placebo | Pioglitazone |
|---|---|---|
| Lost to Follow-up | 2 | 0 |
| Physician Decision | 1 | 0 |
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: M/I
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 | Placebo | Pioglitazone | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 11 | 24 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 13 | 11 | 24 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 55 (SD 7) | 56.6 (SD 9.3) | 55.7 (SD 8.03) |
| Sex: Female, Male: Female | Participants | 4 | 4 | 8 |
| Sex: Female, Male: Male | Participants | 9 | 7 | 16 |
| Region of Enrollment: United States | participants | 13 | 11 | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Whole Body Insulin Sensitivity During the Euglycemic Insulin Clamp, measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | Mg. of glucose/kg body w./mUxl ins. |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is whole-body insulin sensitivity measured by the euglycemic insulin clamp. The registry describes the measure as M/I: M is whole-body glucose uptake during the clamp, and I is circulating insulin levels during the clamp. Its stated unit is Mg. of glucose/kg body w./mUxl ins. The outcome is treated as a continuous measure summarized by a mean, with standard error identified as the dispersion measure.
A clamp is used to assess glucose handling under controlled conditions. In general, relating glucose uptake to circulating insulin provides an index of insulin sensitivity, rather than simply recording glucose or insulin in isolation. The endpoint therefore corresponds to the trial’s stated focus on insulin sensitivity. This general description explains the rationale for the measure; it does not establish what the trial found.
The registry lists assessment before treatment and 6 months after pioglitazone or placebo treatment, with a 6-month timeframe. A treatment comparison would ordinarily need to specify whether it concerns the follow-up value, change from baseline, or an adjusted comparison. The registry record does not state which analytic contrast was used, nor does it report the group means, the estimated difference, or a confidence interval for the primary endpoint. Consequently, the endpoint definition is available, but the size and precision of the trial’s primary result are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically relevant statistical question: whether insulin sensitivity measured by a euglycemic clamp differs between pioglitazone and placebo over the stated treatment period. It describes the primary outcome and study design, but does not report numeric results for that outcome. There are no arm-level means, treatment-effect estimate, confidence interval, or primary-outcome p-value in the record. The direction, magnitude, and precision of the primary comparison therefore cannot be interpreted from these registry entries.
The endpoint is defined as M/I, where M represents glucose uptake during the clamp and I represents circulating insulin during the clamp. The record says the outcome was measured before treatment and 6 months after treatment. It does not specify whether the primary analysis compared follow-up values, changes from baseline, or another contrast. Those choices can matter: a comparison of follow-up values and a comparison of changes do not necessarily answer the same statistical question, particularly if baseline values differ. The registry record does not report which approach was used.
The study is identified as randomized, double-masked, and parallel. In general, randomization is intended to make treatment groups comparable on average, while masking can reduce some forms of bias in treatment delivery and assessment. Those design labels do not by themselves show whether groups were balanced in the enrolled sample, whether masking was maintained, or how missing observations were handled. Such details are not reported in the registry record.
The adverse-event figures are reported separately from the primary endpoint. The record lists zero serious events among the participants at risk in each arm. It lists one other event in the placebo arm and zero in the pioglitazone arm. These counts are descriptive registry entries; they do not establish comparative safety, especially without fuller definitions, follow-up details, or an inferential analysis. Death counts are not reported in the registry record.
The study summary describes proposed investigations of TIMP-3, TACE, insulin sensitivity, and vascular reactivity, among other measures. A biological rationale or a planned set of measurements is not itself evidence of a treatment effect. Since numeric primary results and a full analysis are not reported, no conclusion about whether the observed data support the proposed mechanism or show a change in insulin sensitivity can be drawn from the registry record alone.
Interpretation should therefore stay at the level of design and outcome definition. The record establishes that a completed randomized trial was registered, identifies the intended comparison and endpoint, and includes limited adverse-event counts. It does not provide the outcome estimates needed to judge the magnitude of any difference or how precisely it was estimated. A null or non-null result cannot be inferred from the absence of reported primary-outcome values.
9. Statistical Methods Explained
What does a mean represent?
The registry identifies the primary outcome as a continuous measure and says it is summarized by a mean. A mean describes the central level of measured values in a group. It can be useful for comparing groups, but it does not show the spread or shape of individual observations on its own. In this trial, the measure is M/I from a euglycemic insulin clamp. The registry record does not report the arm means or the treatment contrast, so no numerical comparison can be interpreted.
The record names standard error as the dispersion measure. In general, a standard error describes the statistical uncertainty in an estimate, such as a group mean; it is not the same thing as the standard deviation, which describes variation among individual observations. A standard error can help convey how precisely a mean has been estimated, but it does not by itself show the full range of participant values. The record does not provide the numerical standard errors for the primary outcome.
How should a treatment difference be read?
For a randomized, parallel-group trial, the central treatment comparison is generally a contrast between outcomes in the assigned groups. A contrast needs a clear definition: for example, a comparison at follow-up or a comparison of changes from baseline. The registry records measurements before treatment and at 6 months but does not state which contrast was used for the primary analysis. It also does not provide a treatment-effect estimate.
In general, a confidence interval gives a range of values compatible with the data and the assumptions of the analysis. Its width communicates precision: a narrower interval indicates greater precision than a wider interval. An interval also helps distinguish estimates that are compatible with a range of effects from estimates that are more tightly localized. No confidence interval for the primary comparison is reported in the registry record, so neither its direction nor its precision can be assessed.
A p-value, when reported, summarizes how unusual data at least as inconsistent with a specified null hypothesis would be under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry record does not report a primary-outcome p-value or identify the test used. A p-value should not be inferred from the endpoint description or the study design.
Why does the analysis population matter?
In general, a randomized trial can describe participants according to their assigned treatment, treatment received, or availability of outcome measurements. These approaches answer different questions. An analysis retaining participants in their randomized groups is often used to preserve the intended comparison, while analyses based on treatment received can be affected by differences that arise after randomization. The registry record does not report the analysis population or whether participants were analyzed according to assignment.
Missing outcome measurements can also affect both the number of observations contributing to an estimate and the assumptions behind the analysis. A complete-case analysis uses participants with observed values; other methods may use additional assumptions about unobserved values. The registry record does not report missing primary-outcome counts, reasons for missingness, or methods used to address it. No particular missing-data approach should be presumed.
What do the planning assumptions mean?
The registry’s sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. In general, a planning illustration asks how many participants per arm might be needed under chosen assumptions. It is not an estimate of the probability that this completed trial detected an effect, and it is not observed power.
Planning calculations depend on the effect chosen, variability, significance level, allocation, and other assumptions. A smaller target effect generally requires more information to detect with the same statistical criteria. Such illustrations are conditional on their inputs, not proof that a trial was adequately designed or that an effect exists. The record does not report a sample-size justification from the trial’s original design, so the planning assumptions should not be treated as that justification.
For time-to-event outcomes, planning tables may describe total events, while other planning displays may describe participants per arm. The sample-size assumptions state this distinction. The primary endpoint in this trial is continuous, rather than a time-to-event endpoint. The record does not give numerical planning estimates in the registry record for this analysis, so no required sample size can be stated.
Why might variability need special treatment?
For continuous outcomes, an analysis may need to account for the distribution and variability of the measured values. In general, if observations are more variable than a simple model assumes, standard errors and confidence intervals based on that model may be too optimistic. Over-dispersion refers broadly to variability exceeding what a model allows. Whether it is relevant depends on the outcome and analysis. The registry record does not describe an over-dispersion assessment or a statistical model for the clamp measure, so it would be inappropriate to claim that a particular adjustment was used or needed.
The record notes five analyses and three outcome measures, but does not identify the analysis procedures or provide the complete outcomes. The exact model, covariates, handling of repeated measurements, multiplicity strategy, and any interim analysis are not reported in the registry record. These omissions limit the extent to which the statistical analysis can be independently understood from the registry description.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three outcome measures and five analyses, and identifies TACE activity in skeletal muscle as a secondary outcome. Having multiple outcomes or analyses raises the general issue of multiplicity: when many statistical comparisons are made, the chance of at least one apparently notable result can increase. Researchers may address this through a prespecified hierarchy, adjustment procedures, or clear distinctions between primary and exploratory analyses. The registry record does not report a multiplicity strategy, a hierarchy among the analyses, or which analyses were prespecified.
The primary outcome is whole-body insulin sensitivity during the euglycemic insulin clamp. The record describes measurements before treatment and at 6 months, but does not state the exact primary contrast or analysis model. It also does not give the primary estimate, uncertainty interval, or p-value. No conclusions about statistical evidence or the consistency of findings across outcomes can therefore be drawn from the record.
Missing-data handling is not reported in the registry record. The record does not give the number of missing primary outcome values, reasons for missingness, or whether participants with missing measurements were included through an imputation or model-based approach. In general, missingness can affect both the precision and interpretation of a treatment comparison; the implications depend on why values are missing and how the analysis handles them.
The analysis population is also not reported in the registry record. Although the trial is described as randomized, it is not stated whether the primary analysis followed randomized assignment, treatment received, or another population definition. The record does not report interim analyses, stopping rules, or the statistical analysis plan. These details should be treated as unreported rather than inferred from the trial design or completion status.
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 |
|---|---|---|---|
| Placebo | 0 | 13 | 0.0% |
| Pioglitazone | 0 | 11 | 0.0% |
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 |
|---|---|
| Placebo | 1 of 13 |
| Pioglitazone | 0 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Pioglitazone |
|---|---|---|---|
| anemia | Blood and lymphatic system disorders | 1 of 13 | 0 of 11 |
The registry lists serious adverse-event counts by arm. For placebo, 13 participants are listed at risk for serious events and zero as affected. For pioglitazone, 11 are listed at risk and zero as affected. These are the serious-event figures recorded for the two arms; the record’s serious-event terms list is empty.
The registry also reports other adverse-event counts. For placebo, 13 are listed at risk and one as affected. For pioglitazone, 11 are listed at risk and zero as affected. The record does not give further event descriptions in the registry record for this analysis. Death counts are not reported in the registry record.
These entries are counts, not a complete comparison of safety. The record does not provide event definitions, timing, severity details for the other events, or an inferential analysis. The at-risk figures are not the same as the enrollment figure, and the record does not explain the relationship between them. With limited event reporting, the counts should be read descriptively and should not be used alone to infer comparative risks or to establish that an event could not occur.
12. What the Result Does, and Does Not, Mean
The registry record establishes the intended comparison: pioglitazone versus placebo in a randomized, double-masked, parallel phase 4 trial involving people with type 2 diabetes. It identifies whole-body insulin sensitivity measured by a euglycemic insulin clamp as the primary outcome and describes measurement before treatment and at 6 months. It also reports limited adverse-event counts.
Those design and endpoint details do not reveal the primary treatment result. The registry record does not report arm means, an estimated treatment difference, a confidence interval, or a primary-outcome p-value. It is therefore not possible to describe the size, direction, or precision of the primary comparison from this record. The absence of a reported estimate is not evidence that the groups were the same, nor is it evidence of a treatment effect.
The stated scientific rationale refers to proposed roles for TIMP-3 and TACE in insulin sensitivity and endothelial function. The summary also describes plans to measure biological and vascular outcomes. A proposed mechanism can motivate a trial, but it is distinct from a statistical finding. Without the relevant numerical results and analysis details, the record does not establish whether the proposed measures changed or whether they were related to the primary outcome.
The enrollment and study summary figures are not reconciled: enrollment is listed as 60, while the summary describes thirty subjects. The summary gives a 24-week treatment period, while the arm descriptions state 6 months. These differences are recorded without explanation, so the exact relationship between these descriptions cannot be determined from the registry record.
The appropriate conclusion is limited: the trial design and primary outcome are described, but the primary results and key analysis details are not reported in the registry record. The adverse-event entries are descriptive and limited. They cannot substitute for the missing efficacy estimates, a full safety account, or a transparent account of the analysis population and methods.
13. Why This Trial Matters Statistically
This trial is statistically notable because it links a mechanistic research question to a quantitative physiological endpoint. The investigators’ stated rationale concerns TIMP-3 and TACE, while the registered primary endpoint is M/I from a euglycemic insulin clamp. Separating the biological hypothesis from the primary endpoint is important: the proposed mechanism explains why the study was undertaken, whereas the endpoint specifies what the primary comparison was intended to measure.
The randomized, double-masked, parallel design identifies a structure intended to support a treatment comparison. In general, random allocation can help balance measured and unmeasured participant characteristics on average, and masking can reduce some potential biases. Those features do not replace reporting of the analysis, outcomes, uncertainty, and participant flow. The registry record describes the design but does not report the primary estimates or the statistical methods in enough detail to judge the result.
The record also illustrates why consistent descriptions matter. Enrollment is listed as 60, while the summary describes thirty subjects; the planned treatment period is described as 24 weeks in the summary and 6 months in the arm descriptions. Without an explanation, readers cannot determine how these entries fit together. Clear alignment of enrollment, treatment duration, outcome timepoints, and analysis populations helps readers understand what was measured and which participants contributed to the results.
Finally, the registry reports several outcome measures and analyses but does not describe multiplicity handling or provide primary outcome results. Statistical interpretation depends not only on a design label or a biologically plausible hypothesis, but also on effect estimates, precision, missing-data information, and transparent methods. The record’s limits make it a useful example of the distinction between a registered research question and the evidence needed to evaluate its answer.
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.
The principal limitation for interpreting this trial is that the registry record does not report numeric results for the primary outcome. Group means, the treatment-effect estimate, its confidence interval, and the primary-outcome p-value are not reported in the registry record. Without them, the magnitude, direction, and precision of the primary comparison cannot be assessed.
Several record descriptions are not reconciled. The enrollment field lists 60, whereas the summary describes thirty subjects. The summary refers to a 24-week treatment period, while both arm descriptions state 6 months. The primary outcome timeframe is listed as 6 months. The record does not explain the relationship among these descriptions, and they should not be treated as interchangeable without clarification.
The analysis details are limited. The record does not report the exact primary contrast, statistical model, covariate adjustment, analysis population, handling of missing outcome data, or multiplicity plan. It also does not report the number of participants contributing primary measurements or reasons for any missingness. Those omissions prevent a full assessment of how the endpoint was analyzed and how robust the comparison may be.
The adverse-event entries are also limited. The record lists at-risk and affected counts, but does not give full event descriptions, timing, or an inferential comparison. Death counts are not reported in the registry record. The record’s completion status does not resolve these reporting gaps. Conclusions should therefore remain confined to the trial design and the limited outcomes and counts actually described.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Pioglitazone on TIMP-3 and TACE in Type 2 Diabetes — NCT01223196.
- Registry record last updated 2016-01-11; status last verified 2015-12.
- Results first posted 2014-11-13.
- 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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18. Record Summary
The registry record describes a completed, randomized, double-masked, parallel phase 4 trial comparing pioglitazone with placebo in people with type 2 diabetes. Enrollment is listed as 60. Pioglitazone is described as 15mg once daily, and both arm descriptions state a 6-month treatment period.
The primary outcome is whole-body insulin sensitivity measured by euglycemic insulin clamp as M/I, with a 6-month timeframe. The record states that the outcome was measured before and after treatment and identifies the mean and standard error as the summary and dispersion. Numeric primary-outcome results and the statistical analysis plan are not reported in the registry record.
The record lists TACE activity in skeletal muscle as a secondary outcome. Serious adverse-event counts are zero in both arms; other-event counts are one for placebo and zero for pioglitazone. The record does not report death counts. It also does not explain the difference between the enrollment figure and the number described in the study summary, or the differing treatment-duration descriptions.