Effect of Empagliflozin Kinetics on Renal Glucose Reabsorption in Patients With Type II Diabetes and Healthy Controls: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Empagliflozin Kinetics on Renal Glucose Reabsorption in Patients With Type II Diabetes and Healthy Controls (NCT01867307), a non-randomized phase 2 study. The primary outcome is Change From Baseline of Renal Tubular Maximum Reabsorptive Capacity for Glucose (TmG) at End of Empagliflozin Treatment (Day 14).

2. Clinical Question

In general, a mechanistic study asks about a biological process or measurement rather than relying only on a clinical event. TmG describes the kidney’s maximum capacity to reabsorb glucose, expressed in the registry record in milligrams per minute per 1.73 square meters. Measuring change from baseline focuses the endpoint on within-participant change over the treatment period. However, the record does not provide group means, variability, confidence intervals, or a test of change. The question can therefore be described, but the magnitude and precision of the observed changes cannot be assessed from the registry record.

3. Trial Design

This was a Phase 2, single-center, open-label mechanistic study. The registry record describes a 14-day study of oral empagliflozin at 25 mg q.d. In patients with type 2 diabetes mellitus and healthy controls. It lists the design as parallel, with non-randomized allocation and no masking. The record reports enrollment of 39 participants and a completed status.

The study began in 2013-06, and primary completion was recorded in 2015-10. The listed arms were Healthy Controls and Patients; the latter were described as patients with type 2 diabetes mellitus. The intervention list includes Empagliflozin and BI 10773, both categorized as drugs. The record does not explain why both names appear or specify how each listed intervention maps to the study arms.

Non-randomized allocation matters when interpreting comparisons. The patient and healthy-control groups differ by health status by design, and the registry record does not describe random assignment to treatment or a randomized untreated control group. As a result, differences between these groups cannot be attributed to empagliflozin alone. The study’s central endpoint is a change from baseline during treatment, but the record does not provide a numerical estimate of that change.

The primary analysis population was described as the per-protocol set, consisting of participants who completed the Day 14 clamping study without relevant deviations in treatment or measurement performance and timing. The registry also describes an analysable set based on that population, with endpoint data excluded for one healthy subject because of outlying TmG and urine splay values. Further details about the number included in each endpoint analysis and the handling of other incomplete data are not reported in the registry 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysable set (AS): This data set is based on the PPS and excluded all primary endpoint and exploratory endpoint data for one healthy subject due to outlying values that were identified in the subject's TmG and urine splay data.

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.

Population: The treated set (TS) consisted of all subjects and patients who were treated with at least one dose of empagliflozin.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline of Renal Tubular Maximum Reabsorptive Capacity for Glucose (TmG) at End of Empagliflozin Treatment (Day 14), measured over Baseline and Day 14.

The primary endpoint was change from baseline in renal tubular maximum reabsorptive capacity for glucose (TmG) at the end of empagliflozin treatment on Day 14. The measure is reported as a mean, with standard deviation as the stated measure of dispersion. Its unit is milligrams per minute per 1.73 square meters, and the specified timeframe is baseline and Day 14.

TmG is a measure of the kidney’s capacity to reabsorb glucose. In general, a maximum-capacity measure can help characterize how a physiological process behaves when it approaches its limit. Measuring the change from baseline provides a way to describe how that measure shifts over the treatment period within the analysed population. This mechanistic endpoint is distinct from a clinical outcome such as a symptom, complication, or long-term health event.

The registry record identifies the endpoint and the population definition, but gives no numerical mean change, standard deviation, confidence interval, or statistical test result. It therefore does not establish the direction, size, or precision of the endpoint change. The rationale for selecting TmG as the primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint was analysed?

The primary endpoint was continuous: a change in TmG from baseline to Day 14. The registry describes the analysis parameter as a mean and the dispersion measure as a standard deviation. In general, continuous outcomes can take a range of values, so analysis often focuses on quantities such as means and variability rather than event counts. Here, the record does not include the actual mean change or standard deviation, so no numerical estimate can be interpreted.

What does a standard deviation convey?

In general, a standard deviation describes how spread out observations are around their mean. It is not the same as the uncertainty around the estimated mean. A confidence interval is one way to express uncertainty about an estimate: it gives a range of values compatible with the data and the method used to calculate it. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be judged from that measure.

Why does the allocation matter?

Allocation was non-randomized, and the study was open-label. In general, randomization helps balance measured and unmeasured participant characteristics between treatment groups, on average. Without random assignment, groups may differ for reasons other than the intervention. Masking can reduce some influences on measurement or assessment; no masking was reported for this study. These design features do not invalidate the descriptive endpoint, but they limit how strongly a comparison can support a causal interpretation. The registry record does not report an adjusted analysis that accounts for group differences.

What does the analysis population mean?

The per-protocol set was defined as participants who completed the Day 14 clamping study without relevant deviations in treatment or in the performance and timing of measurements. In general, per-protocol analyses focus on participants who followed specified study procedures, but their results may not represent everyone enrolled. The analysable set was based on the per-protocol set and excluded endpoint and exploratory endpoint data for one healthy subject because of outlying TmG and urine splay values. The record does not give the final number included in each endpoint analysis or describe any alternative analysis retaining those values.

What can the sample-size illustrations say?

The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, the stated convention is participants per arm; the effect to detect is expressed as a stated fraction of the observed effect. Such illustrations are planning calculations, not evidence that a study had a particular probability of detecting its effect. They are not observed power. The registry record does not provide the numerical outputs of those illustrations in the registry record described for this analysis, and the illustrations should not be confused with the trial’s own design justification. The sample-size justification for the trial is not reported in the registry record.

What do unreported tests and multiplicity mean?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of a statistical test. It does not measure the size or clinical importance of an effect. A confidence interval adds information about the range of estimates compatible with the data and method. Neither a p-value nor an interval for the primary endpoint is reported in the registry record. The record also does not describe the statistical test used, any covariate adjustment, or assumptions checked for the endpoint analysis.

Multiplicity arises when several outcomes, groups, or analyses are tested, increasing the chance of at least one apparently notable result if no adjustment or pre-specified interpretation strategy is used. The registry lists one outcome measure and two analyses, but does not explain their relationship or report a multiplicity strategy. The existence of multiple analyses alone does not establish that a correction was needed or used. The statistical analysis plan, including any interim analyses, is not reported in the registry record.

How should sparse event counts be read?

For adverse events, the registry provides counts of participants at risk and affected in each group. In general, event counts describe what was recorded in the study population and period; they do not establish that an event was caused by treatment. Small event counts can also yield imprecise comparisons. The record does not provide a comparative statistical analysis of adverse events, and the non-randomized design further limits causal interpretation.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("T2DM Patients", "Healthy Subjects")
n   <- c(15, 15)
m   <- c(-321.7, -256.9)
sp  <- c(214.9, 100)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  T2DM Patients  15  -321.700  214.900  -440.708  -202.692
CARM  Healthy Subjects  15  -256.900  100.000  -312.278  -201.522

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and two analyses, but does not explain how those analyses relate to one another. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a statistical analysis plan that would clarify which results were confirmatory. The presence of multiple analyses does not by itself show that a particular adjustment was required or applied. Interim analyses are not reported in the registry record.

The endpoint description identifies a per-protocol set and an analysable set. The per-protocol set included participants who completed the Day 14 clamping study without relevant treatment or measurement deviations. The analysable set was based on that set and excluded endpoint and exploratory endpoint data for one healthy subject because of outlying TmG and urine splay values. This is a stated exclusion, but the record does not report the impact of retaining those data in an alternative analysis.

Other details about missing data are not reported in the registry record. In particular, it does not describe the amount or reasons for any other missing endpoint data, an imputation method, or sensitivity analyses for missingness. The final analysis count for the primary endpoint is not reported in the registry record. These omissions make it difficult to assess whether the analysed data represent all participants who entered the study or how robust the endpoint estimate would be to different analysis-population choices.

The record also does not report the statistical model, any adjustment for baseline or other covariates, or assumptions used for the primary endpoint. Since numerical endpoint results are absent, neither the outcome of any analysis nor the effect of these methodological choices can be assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts of 0 among 18 participants at risk in the T2DM Patients group and 0 among 19 participants at risk in the Healthy Subjects group. No serious adverse event terms are listed. These are recorded counts for the study groups, not a randomized comparison of treatment and control.

For other adverse events, the record reports 14 affected among 18 at risk in the T2DM Patients group and 16 affected among 19 at risk in the Healthy Subjects group. These figures are counts of participants affected; the registry does not provide event-level descriptions in the registry record. Death counts are not reported in the registry record.

In general, adverse-event counts describe events observed and recorded during a study; they do not establish whether treatment caused an event. The study was open-label and non-randomized, and its 14-day treatment period limits what can be inferred about events outside that period. No comparative statistical analysis of the safety counts is reported. The figures should therefore be read as descriptive safety reporting, not as proof of a difference between groups or as evidence about longer-term safety.

13. What the Result Does, and Does Not, Mean

The record documents a mechanistic study of empagliflozin in patients with type 2 diabetes and healthy controls, with change in TmG from baseline to Day 14 as the primary endpoint. It also describes the study’s open-label, non-randomized, parallel-group design and the populations used for endpoint analysis. These details establish the question and analysis context, but the registry record does not report the numerical results for the primary endpoint.

Consequently, the record does not show whether mean TmG changed, in which direction it changed, or how large or precise any change was. It does not report the primary endpoint’s standard deviation, confidence interval, or p-value. No conclusion about the magnitude or statistical uncertainty of the endpoint can be drawn from the information reported.

Even if numerical results were available, the non-randomized comparison between patients and healthy controls would require cautious interpretation. In general, group differences may reflect characteristics beyond the treatment, and an open-label design can affect measurement or reporting. The within-group change over the treatment period would describe the observed change in the analysed population; on its own, it would not establish what would have happened without treatment.

The adverse-event counts are descriptive and do not resolve these limitations. They record serious and other adverse events in the study groups, but do not establish causation or provide a randomized safety comparison. The study’s short treatment period also does not address outcomes outside its observed period.

Overall, the registry record allows a clear account of the endpoint and study design, but not an assessment of the primary result. A mechanistic measurement can contribute information about a biological process, yet it is not interchangeable with evidence about clinical outcomes. The record does not report the rationale for the endpoint, a clinical outcome assessment, or numerical results connecting TmG changes to such outcomes.

14. Why This Trial Matters Statistically

This trial is statistically notable because it focuses on a mechanistic continuous endpoint and describes its analysis population in some detail. TmG measures renal glucose reabsorptive capacity, and the primary question concerns change from baseline during a defined treatment period. Such an endpoint can be useful for characterizing a physiological process, but interpreting it depends on seeing the estimated change and its uncertainty. Those numerical results are not reported in the registry record.

The study also illustrates why design labels matter. A parallel structure does not make the groups comparable by itself. Because allocation was non-randomized and the groups were patients with type 2 diabetes and healthy controls, a contrast between groups would be vulnerable to differences associated with health status and other characteristics. Open-label conduct adds another consideration for measurement and reporting. The record does not describe adjustment methods that might address these issues.

Analysis-population definitions affect what an estimate represents. The per-protocol set required completion of the Day 14 clamping study without relevant deviations, while the analysable set excluded data for one healthy subject because of outlying measurements. These choices should be understood alongside any reported endpoint estimates; here, no such estimates are reported, and the record does not describe sensitivity analyses.

Finally, the registry’s sample-size illustrations are planning tools based on an observed effect and stated assumptions, rather than evidence of observed power or of the trial’s original design rationale. This distinction helps separate design planning from analysis of collected data. Overall, the record offers useful information about design and measurement, while leaving the central quantitative result unavailable.

15. 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 limitation for interpreting efficacy is that the registry record describes the primary endpoint without reporting its numerical results. No mean change, standard deviation, confidence interval, or p-value is reported. The direction, magnitude, and precision of the measured change therefore cannot be assessed.

The study was open-label and non-randomized, with patients and healthy controls in parallel groups. This design does not provide a randomized, like-for-like control comparison. Differences between groups could reflect factors other than the treatment, and a within-group change alone cannot identify what would have happened in the absence of treatment. The record does not report an adjusted analysis that would clarify how measured group differences were handled.

The stated per-protocol definition depends on completing the Day 14 clamping study without relevant deviations in treatment or measurement. The analysable set further excluded endpoint and exploratory endpoint data for one healthy subject because of outlying TmG and urine splay values. The record does not report sensitivity analyses to show how this exclusion affected the endpoint, or give the final number analysed for the primary endpoint.

The record does not report other details needed to evaluate the analysis fully, including the statistical model, missing-data methods, multiplicity strategy, or interim analyses. The sample-size justification for the trial is also not reported in the registry record. The 14-day treatment period and mechanistic endpoint limit conclusions to the measured process and study period; longer-term outcomes are not addressed by the endpoint described.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Empagliflozin Kinetics on Renal Glucose Reabsorption in Patients With Type II Diabetes and Healthy Controls — NCT01867307.
• Registry record last updated 2017-05-11; status last verified 2017-03.
• Results first posted 2017-05-11.
• 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.

19. Record Summary

This completed Phase 2 study examined oral empagliflozin at 25 mg q.d. In patients with type 2 diabetes mellitus and healthy controls. It was single-center, open-label, non-randomized, and parallel, with a 14-day treatment period. The registry reports enrollment of 39 participants, a start in 2013-06, and primary completion in 2015-10.

The primary endpoint was change from baseline in renal tubular maximum reabsorptive capacity for glucose (TmG) at Day 14, reported as a mean with standard deviation. The registry describes a per-protocol set and an analysable set that excluded data for one healthy subject because of outlying values. Numerical primary endpoint results and their uncertainty are not reported in the registry record.

Serious adverse event counts were 0 in both listed groups; other adverse events were reported in both groups. The non-randomized design means the patient and healthy-control groups are not a like-for-like treatment comparison.