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 Adding an Insulin-Sensitizing Medication to Depression Treatment for People Who Are Depressed and Overweight (NCT00834652), a randomized phase 4 study. The primary outcome is Change of Beck Depression Inventory-II Scores Over 16 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00834652 |
| Phase | Phase 4 |
| Condition | Depression |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 206 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned people who were depressed and overweight. Depression is the listed condition. Further eligibility criteria and the characteristics of participants enrolled are not reported in the registry record, so the population cannot be described more narrowly.
Intervention
Participants in the intervention arm were assigned to receive sertraline and metformin. The registry summary describes the study as testing whether adding metformin improves the effects of traditional antidepressant medication in people who are overweight. Details such as doses and treatment schedules are not reported in the registry record.
Comparator
The comparison arm received sertraline and placebo. This makes the intended contrast the addition of metformin to sertraline versus sertraline with placebo. The registry record does not report further details about how the placebo was administered or how treatment adherence was assessed.
Primary question
The listed primary outcome is change in Beck Depression Inventory-II scores from baseline to 16 weeks. The scale ranges from 0 to 63, and higher scores represent a worse outcome. The registry record does not report a single numerical comparison of change between the randomized arms, so the size and precision of any between-arm difference cannot be assessed from that record.
3. Trial Design
This was a phase 4, randomized, parallel-group trial with quadruple masking. The registry lists enrollment of 206 and identifies Washington University School of Medicine as the sponsor. The recorded start was 2007-09, primary completion was 2013-05, and the status is completed. These details describe the registered design and conduct milestones; they do not establish how many participants contributed data to the primary outcome.
The two registered arms were sertraline plus metformin and sertraline plus placebo. Randomization supports an intended comparison between those assignments, while masking is intended generally to reduce the influence of treatment knowledge on participants, care providers, investigators, or outcome assessment. The registry does not specify which roles were included in the quadruple masking designation or how masking was maintained.
The primary outcome is described as change in Beck Depression Inventory-II scores over 16 weeks, measured at baseline and 16 weeks. Although the record lists one outcome measure and one analysis, it does not report the analysis population, the number of participants with outcome data, the statistical model, or a numerical result for a single between-arm comparison. It also does not report the allocation ratio, dose and schedule details, adherence information, or a sample-size justification. Those omissions limit how fully the realized analysis can be compared with the registered design.
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 | Sertraline Plus Metformin | Sertraline Plus Placebo |
|---|---|---|
| STARTED | 104 | 102 |
| COMPLETED | 66 | 62 |
| NOT COMPLETED | 38 | 40 |
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 | Sertraline Plus Metformin | Sertraline Plus Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 104 | 102 | 206 | |
| Age, Continuous | years | 43.67 (20 to 60) | 42.15 (22 to 58) | 42.91 (20 to 60) |
| Sex: Female, Male: Female | Participants | 86 | 85 | 171 |
| Sex: Female, Male: Male | Participants | 18 | 17 | 35 |
| Region of Enrollment: United States | participants | 104 | 102 | 206 |
| Marital Status (married) | participants | 48 | 45 | 93 |
| Education | years | 14.64 (10 to 18) | 14.60 (8 to 20) | 14.62 (8 to 20) |
| Baseline Body Mass Index (BMI) | kg/m^2 | 38.53 (27.44 to 59.23) | 38.07 (27.80 to 58.42) | 38.30 (27.44 to 59.23) |
6. Primary Endpoint
The registry lists the primary outcome as Change of Beck Depression Inventory-II Scores Over 16 Weeks, measured over Measured at Baseline and 16 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in Beck Depression Inventory-II (BDI-II) scores over 16 weeks, with measurements at baseline and 16 weeks. The BDI-II is described as a scale from 0 to 63, where higher scores represent a worse outcome. A change score expresses how a participant’s measured score differs between the two assessment times; comparing change between randomized arms can describe whether the groups followed different average score trajectories over the treatment period.
As a general measurement point, a validated symptom scale can represent a clinical concept consistently and give researchers a quantitative outcome for statistical comparison. The mean summarizes the average score change in a group, while the standard deviation describes how spread out individual scores are around that mean. These summaries do not show every participant’s experience, and a group average does not indicate that all participants changed in the same direction.
The registry record specifies the endpoint and its scale but does not report a single usable comparison of score change between arms. It therefore does not establish the observed average change in either arm, the difference between those changes, or the uncertainty around such a difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registered question is whether adding metformin to sertraline is associated with a different change in BDI-II scores over 16 weeks than sertraline with placebo. The record identifies this endpoint, its assessment times, and its direction: higher scores represent a worse outcome. However, it does not report a single numerical comparison of the primary outcome between the arms. No arm-specific mean changes, between-arm estimate, confidence interval, or p-value for that comparison is reported in the registry record.
As a general statistical point, the between-arm contrast is more informative for a randomized trial than interpreting change within one arm alone. Participants may change over time for reasons shared across arms, and a within-arm change does not by itself isolate the effect associated with the difference in assigned treatment. The intended randomized comparison accounts for this by comparing outcomes across the assigned groups, subject to the analysis approach and completeness of outcome data.
The registry describes the primary measure using a mean and standard deviation, which are useful summaries for a continuous outcome. The mean represents the group average; the standard deviation describes variation among observations. Without the reported means and uncertainty for the treatment contrast, neither the direction nor the magnitude of the primary between-arm result can be assessed. The scale’s range and scoring direction alone do not reveal what happened in the trial.
The record lists one outcome measure and one analysis, but that does not supply the missing estimate or clarify how the analysis was carried out. The primary outcome is also flagged as involving several categories or time points and not being reduced to one comparison. Thus, the registry record does not support a numerical conclusion about the primary endpoint’s treatment contrast. A lack of a reported comparison is not evidence that the arms were identical, nor does it show that a difference was present.
The enrollment figure is 206, but enrollment is not the same as the number analyzed for this endpoint. The number with baseline and 16-week BDI-II data, the handling of incomplete observations, and the analysis population are not reported in the registry record. Those details would matter when assessing how representative the analyzed data are of the randomized participants and how precise an estimate might have been.
9. Statistical Methods Explained
The registry identifies a randomized, parallel-group design. In general, random assignment is intended to make the treatment groups comparable at the point of assignment, including with respect to measured and unmeasured factors on average. It does not guarantee exact balance in a particular trial, and the registry record does not give baseline characteristics or details of the randomization procedure. The parallel structure means participants were assigned to one of the listed treatment combinations rather than being described as switching between them.
What does quadruple masking mean?
Masking is intended to reduce the influence of knowing an assignment on reported symptoms, clinical care, outcome assessment, or analysis decisions. The record calls the trial quadruple masked, but it does not identify the four roles covered by that label or explain when masking was maintained or assessed. The label therefore describes the registered masking designation, not a complete account of its implementation.
How should a continuous endpoint be summarized?
The primary measure is continuous: BDI-II scores are recorded on a numeric scale, and the registered parameter is the mean with standard deviation as the dispersion measure. As a general statistical explanation, a mean gives the arithmetic average of observations, whereas a standard deviation describes how much individual observations vary around that average. The mean is useful for describing a group-level score, but it can conceal differences among participants and may be affected by unusually high or low observations.
For a randomized comparison based on change scores, the analysis would need to define how baseline and 16-week scores are combined and how the arms are contrasted. The registry gives the measurement times and says baseline scores are compared with scores after treatment, but the exact statistical model, covariate adjustment, and definition of the reported contrast are not reported in the registry record. No model should be inferred from the endpoint description alone.
What would a confidence interval add?
As a general statistical point, a confidence interval describes the uncertainty associated with an estimated contrast under the assumptions of the analysis. Its width reflects both the variability in the data and the amount of information available. It can help readers judge which effect sizes remain compatible with the data; it is not a guarantee that the true effect lies within a particular interval. No confidence interval for the primary comparison is reported in the registry record, so its precision cannot be evaluated.
A p-value, when reported, measures how incompatible the observed data are with a specified null model under the assumptions of the test. It does not measure the probability that the null hypothesis is true, nor does it describe the clinical importance of an effect. The registry record does not report a p-value for a single primary comparison. A p-value alone would also be insufficient to describe effect magnitude or precision.
What do the planning assumptions mean?
The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrations are defined for detecting a stated fraction of the observed effect. As a general explanation, such calculations explore how a hypothetical design might perform under specified assumptions; they are not evidence that the trial had that design, and they are not observed power. The registry record does not report the trial’s own sample-size justification. Planning figures should therefore not be treated as observed outcomes or as proof that the trial was adequately powered.
For continuous outcomes, a planning calculation depends on assumptions about the effect to detect and variability, among other design choices. The registry’s description does not provide a basis for independently assessing whether those assumptions matched the trial’s original plan. The recorded enrollment of 206 is a trial-level enrollment figure, not an outcome estimate and not a substitute for knowing the number included in the primary analysis.
Why does variation matter?
As a general statistical point, greater variability among individual scores makes it harder to estimate a group contrast precisely when other design features are held constant. The standard deviation is one way to describe that variation for a continuous measure. If the outcome distribution has features poorly represented by a mean and standard deviation, other summaries or modeling choices may also be relevant. The registry record does not provide enough outcome data to assess distributional shape or determine whether the stated summary was appropriate in practice.
Overall, the record supplies a design label, an endpoint definition, and a description of planning assumptions, but not the primary estimate or the analysis details needed to evaluate its numerical result. Statistical methods can explain what those items would mean, but they cannot fill in an unreported trial result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and one analysis, but it does not report a single primary comparison after reduction of the listed categories or time points. The outcome is flagged as involving several categories or time points and not being reduced to one comparison. The registry record does not explain how those categories or times were handled, which result was considered primary for inference, or whether any multiplicity adjustment was used.
As a general statistical point, testing several outcomes, time points, or contrasts can increase the chance of obtaining an apparently unusual result by chance if each test is treated as an independent primary test. Prespecifying a primary contrast or using an adjustment can help address that issue. The applicable approach depends on the planned hypotheses and analysis; it is not possible to infer one from the count of registered outcomes or analyses. A multiplicity plan is not reported in the registry record.
The record does not report methods for missing BDI-II observations, such as assumptions about why measurements were unavailable, imputation, or sensitivity analyses. It also does not report the number of participants with usable baseline and 16-week scores. Consequently, the impact of incomplete outcome data cannot be assessed from the registry record.
The analysis population is not reported in the registry record. It is therefore unclear whether the primary analysis was based on all randomized participants, participants who received assigned treatment, or another defined group. The enrollment figure does not establish the analysis denominator. Without these details and the numerical result, readers cannot evaluate how missingness, participant exclusions, or analysis-population choices may have affected the primary comparison.
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 |
|---|---|---|---|
| Sertraline Plus Metformin | 0 | 104 | 0.0% |
| Sertraline Plus Placebo | 1 | 102 | 1.0% |
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 |
|---|---|
| Sertraline Plus Metformin | 44 of 104 |
| Sertraline Plus Placebo | 41 of 102 |
Most frequent serious adverse event terms
| Event term | Organ system | Sertraline Plus Metformin | Sertraline Plus Placebo |
|---|---|---|---|
| Syncopal episode leading to inpatient hospitalization | Psychiatric disorders | 0 of 104 | 1 of 102 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sertraline Plus Metformin | Sertraline Plus Placebo |
|---|---|---|---|
| Fatigue | Nervous system disorders | 42 of 104 | 36 of 102 |
| Insomnia | Nervous system disorders | 35 of 104 | 33 of 102 |
| Headache | Nervous system disorders | 28 of 104 | 32 of 102 |
| Diarrhea | Gastrointestinal disorders | 28 of 104 | 22 of 102 |
| Flatulence | Gastrointestinal disorders | 25 of 104 | 21 of 102 |
| Indigestion | Gastrointestinal disorders | 26 of 104 | 20 of 102 |
| Sweating | Nervous system disorders | 27 of 104 | 19 of 102 |
| Bloating | Gastrointestinal disorders | 24 of 104 | 14 of 102 |
| Sexual Dysfunction | Vascular disorders | 20 of 104 | 17 of 102 |
| Dry mouth | General disorders | 18 of 104 | 13 of 102 |
Serious events with the highest arm-level rate: syncopal episode leading to inpatient hospitalization (1.0%).
The registry reports serious adverse events for the two treatment groups. For sertraline plus metformin, the serious-adverse-event figures are 0 affected among 104 at risk. For sertraline plus placebo, they are 1 affected among 102 at risk. The record also lists the serious event term “Syncopal episode leading to inpatient hospitalization” at 1.0%. These are registry-reported safety counts, not a comparison adjusted for differences in follow-up or other factors.
The same record lists other adverse events as 44 among 104 at risk for sertraline plus metformin and 41 among 102 at risk for sertraline plus placebo. Those figures are separate from the serious-adverse-event counts. The registry record does not provide further detail about event severity classifications, timing, recurrence, or attribution to a particular treatment. Deaths are not reported in the registry record.
As a general statistical point, an event count describes what was recorded in the study, while a causal conclusion requires careful interpretation of the trial design, event definitions, exposure, and comparative analysis. These figures alone do not establish whether treatment caused an event or whether the groups differed meaningfully in safety. The serious-event information should be read as descriptive registry reporting, not as a complete safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the trial was designed to compare sertraline plus metformin with sertraline plus placebo in people described as depressed and overweight. It identifies BDI-II score change over 16 weeks as the primary outcome and states that higher scale scores represent a worse outcome. Those details clarify the clinical question and the intended measure, but they do not provide the primary result.
The registry does not report a single numerical comparison of BDI-II change between the arms. As a result, it does not establish the direction, size, or precision of a between-arm difference in the primary outcome. It also does not show whether the result met a prespecified statistical threshold, because no p-value for a single primary comparison is reported. The absence of a reported comparison should not be interpreted as evidence of no difference or evidence of a difference.
As a general statistical point, even a reported difference would need to be considered alongside its uncertainty, the outcome scale, the analysis population, missing data, and the clinical context. Statistical significance alone would not establish importance to participants, and a non-significant result would not demonstrate equivalence. The registry record does not report an equivalence or non-inferiority framework.
The serious adverse event counts are descriptive and do not by themselves establish causation. Nor do they replace a full assessment of safety outcomes. Details about event attribution and other aspects of safety are not reported in the registry record.
Accordingly, the record can be used to understand the registered design, comparator, and endpoint, but it cannot support a conclusion about the primary treatment contrast. The completed status and enrollment figure describe trial conduct, not the effect estimate. A reader seeking the trial’s primary numerical finding would need a result that is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it frames an add-on treatment question: both arms include sertraline, while the assigned additional treatment is metformin or placebo. In general, this kind of comparator can help isolate the contrast associated with the added treatment, provided that randomization, outcome measurement, and analysis are implemented as intended. The registry identifies randomization and quadruple masking but does not provide enough detail to assess implementation fully.
The primary endpoint is a continuous symptom scale measured at baseline and 16 weeks. Continuous outcomes can preserve more gradation than a simple event/no-event outcome, while their interpretation depends on the scale, the summary measure, and the contrast being estimated. Here the scoring direction and range are defined, but a single between-arm result is not reported. The design question is therefore identifiable, while its numerical answer is not available from the registry record.
The record also illustrates why registration details and results serve different purposes. Design information can identify the intended population, intervention, comparator, and endpoint. Interpretation of the trial’s findings additionally requires an estimate, a measure of uncertainty, and adequate information about outcome completeness and analysis choices. The registry’s enrollment figure and completed status cannot replace those results.
Planning illustrations can help describe hypothetical design requirements under stated assumptions, but they are not a measure of the information actually obtained or of observed power. The registry record distinguishes those illustrations from the trial’s own design justification, which is not reported. This distinction matters when interpreting sample-size planning alongside a missing primary result.
The key statistical lesson is that a clearly specified outcome and randomized design do not, on their own, establish what the data showed. Transparent reporting of the treatment contrast and its precision is needed to connect the design to an interpretable result.
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 main trial-specific limitation for interpreting the registered primary question is that the registry does not report a single numerical comparison of BDI-II change between the arms. Arm-level means, a between-arm estimate, uncertainty intervals, and a p-value for that comparison are not reported in the registry record. Without these, the primary endpoint cannot be interpreted quantitatively.
The outcome is described as involving several categories or time points and is not reduced to one comparison. The record does not explain how those elements were selected or combined, so the intended inferential contrast is not fully clear. Although one outcome measure and one analysis are listed, those labels do not resolve the lack of a reported primary comparison.
The registry does not report the number of participants with usable endpoint data, the analysis population, or methods for handling missing observations. Enrollment of 206 does not establish how many participants contributed to the endpoint analysis. Baseline outcome summaries and other participant characteristics are also not reported in the registry record, limiting assessment of the enrolled sample and observed variation.
Details needed to evaluate implementation are not reported, including dose and schedule information, adherence, the allocation ratio, and the roles covered by quadruple masking. The record also does not report the protocol’s sample-size justification, a multiplicity plan, or the statistical model for the primary outcome. These omissions do not show that the trial lacked such procedures; they mean they cannot be assessed from the registry record.
The safety figures are descriptive, with no further reported information about event attribution or timing. Taken together, these limitations mean that the registry record supports description of the planned comparison and some safety counts, but not a complete evaluation of the primary result or its robustness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Adding an Insulin-Sensitizing Medication to Depression Treatment for People Who Are Depressed and Overweight — NCT00834652.
- Registry record last updated 2018-09-10; status last verified 2018-08.
- Results first posted 2018-02-28.
- 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 describes a completed phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Washington University School of Medicine. Enrollment was 206; the recorded start was 2007-09 and primary completion was 2013-05.
The trial compared sertraline plus metformin with sertraline plus placebo in people described as depressed and overweight. The primary outcome was BDI-II score change from baseline to 16 weeks, on a scale from 0 to 63 where higher scores represent a worse outcome. The registry does not report a single numerical between-arm comparison for that outcome, or the analysis population and missing-data methods.
Serious adverse-event figures were 0 affected among 104 at risk in the sertraline-plus-metformin group and 1 affected among 102 at risk in the sertraline-plus-placebo group. The listed serious event term was syncopal episode leading to inpatient hospitalization at 1.0%. These safety counts are descriptive and do not establish causation.