Effects of Dapagliflozin 10 mg on Insulin Resistance in Patients With Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Dapagliflozin 10 mg on Insulin Resistance in Patients With Type 2 Diabetes Mellitus (NCT02426541), a randomized phase 4 study. The primary outcome is Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake.

2. Clinical Question

3. Trial Design

The registry describes a Phase IV, randomized, parallel-group, double-blind, placebo-controlled study at a single centre. The study period for the intervention was 8 weeks. The stated purpose was to evaluate the effect of dapagliflozin on tissue-specific insulin sensitivity in people with Type 2 Diabetes Mellitus. The intervention was dapagliflozin 10 mg once daily, and the comparator was matching placebo.

The registry lists enrollment of 55. The primary outcome results are identified as belonging to the full analysis set, and the outcome group counts are 15 for dapagliflozin and 16 for placebo. The safety record lists 16 participants at risk in each group. The relationship among registry enrollment, outcome counts and safety counts is not reported in the registry record. Reasons for any differences in those counts are also not reported in the registry record.

The primary endpoint was adjusted change from baseline in skeletal muscle insulin-stimulated glucose uptake, measured from baseline to Week 8 in umol/min/kg. The posted results describe group estimates as least-squares means and give standard errors as the measure of dispersion. The registry also lists adjusted adipose and liver insulin-stimulated glucose uptake outcomes over the same period.

The registry record reports an ANCOVA analysis of the primary comparison, with the parameter described as a mean difference in final values. It does not report the covariates, model specification, missing-data method, randomization procedure, allocation concealment details, or a sample-size justification. These details cannot be inferred from the trial design label. The planning figures associated with the posted outcomes are illustrations based on observed effects, not evidence of the study's original design target.

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: Full analysis set

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: Population represents the full analysis set which includes all randomised subjects who received at least one dose of study with a non-missing baseline value and at least one post-baseline value for at least one primary or secondary efficacy variable during the double-blind period.

6. Primary Endpoint

The registry lists the primary outcome as Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake, measured over From baseline to Week 8.

The primary endpoint was adjusted change from baseline in skeletal muscle insulin-stimulated glucose uptake from baseline to Week 8, measured in umol/min/kg. It is a continuous measure: each participant's outcome can take a range of numeric values rather than being limited to a category such as yes or no. The reported group values are least-squares means, with standard errors describing the precision of those estimates.

Insulin-stimulated glucose uptake is used in this study as a measure related to insulin sensitivity in a specified tissue. Focusing on skeletal muscle makes the endpoint tissue-specific rather than a general clinical event or whole-body outcome. The registry also lists adipose and liver insulin-stimulated glucose uptake as secondary measures, giving the study a set of tissue-specific outcomes.

In general, an adjusted change endpoint aims to describe change while accounting for factors included in the statistical adjustment. However, the covariates used for this adjustment are not reported in the registry record. The outcome is a physiological measure, not a direct measure of symptoms, daily function, complications, or long-term clinical outcomes. The registry record therefore supports interpretation of the reported uptake estimates, but does not establish how they relate to outcomes beyond the measures recorded in this study.

7. Results Posted in the Registry

• Dapagliflozin 10 MG: mean 0.28 versus 0.28 on control; difference 0.00 (95% CI -3.27 to 3.27), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Dapagliflozin 10 MG: mean 1.04 versus -0.64 on control; difference 1.68 (95% CI -2.29 to 5.65), standardized effect d = 0.30; z-test p = 0.407.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dapagliflozin 10 MG and the control. The interval gives the range of effects that remain compatible with the data.

Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Dapagliflozin 10 MG: mean 0.27 versus 1.59 on control; difference -1.32 (95% CI -5.85 to 3.21), standardized effect d = -0.21; z-test p = 0.568.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dapagliflozin 10 MG and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the study's tissue-specific focus beyond skeletal muscle to adipose tissue and liver insulin-stimulated glucose uptake. Their estimated directions differ: the adipose comparison points in a positive direction for dapagliflozin relative to placebo, while the liver comparison points in the opposite direction. The confidence intervals for both secondary comparisons include no difference. This mixed directional pattern does not provide a consistent secondary signal that would reinforce the primary result.

The secondary findings do not change the central interpretation of the primary outcome. The primary estimate is close to zero, while its confidence interval remains broad. The secondary estimates are also uncertain, and their confidence intervals permit no difference as well as differences in either direction. Taken together, the outcomes describe an exploratory pattern across tissues rather than a precise, unified estimate of change in insulin sensitivity.

In general, when several outcomes are examined, the chance of obtaining at least one apparently notable result by chance can increase. Adjustment for multiplicity or a prespecified hierarchy can help govern interpretation, but any such approach for these outcomes is not reported in the registry record. Unadjusted secondary p-values therefore carry less weight than a primary result designated in advance, particularly when the number of planned comparisons and the interpretation strategy are unclear. The registry lists two secondary outcomes, but does not report whether they were designated for confirmatory testing or how their results were intended to affect conclusions.

The secondary results should be considered alongside their own uncertainty and the limited outcome counts, not as independent proof of a broader effect. They can identify areas for further study, but the registry record does not report a plan for confirmation or provide longer-term clinical outcomes. No conclusion about clinical benefit or harm follows from these secondary physiological comparisons alone.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake
• Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports an ANCOVA for the primary comparison and describes its parameter as a mean difference in final values. It also posts least-squares mean changes and standard errors for each group. These are related but not identical ways of presenting an analysis: the group summaries describe estimated values within each arm, while the between-group comparison directly quantifies a contrast. The covariates and detailed model specification for the ANCOVA are not reported in the registry record.

What does a mean difference represent?

In general, a mean difference subtracts the comparator-group mean from the intervention-group mean under the stated comparison convention. A value near zero indicates that the estimated group means are close on the scale being analysed. The sign indicates the direction of the contrast, but interpretation also depends on which group is subtracted from which and on what a higher outcome value means. Here, the sponsor reports a primary mean difference of -0.003, while the recalculation from the posted group summaries is 0.0. Those estimates are both very close to zero; their small numerical distinction does not change the broad reading of the result.

What does the standard error tell us?

In general, a standard error describes the statistical uncertainty in an estimated mean. It is not the same as the spread of individual participant measurements. A smaller standard error generally indicates a more precise estimate, while a larger one indicates greater uncertainty. The primary group standard errors are 1.23 and 1.13. The registry reports standard errors as the dispersion measure for the least-squares means, and does not separately post the individual-level outcome distributions.

Why compare the groups directly?

A within-group estimate describes the observed or adjusted change in one arm. It does not by itself answer whether the intervention group differs from the placebo group. A direct between-group contrast is needed for that question. In general, a confidence interval around the contrast conveys both its estimated direction and the uncertainty around its size. The sponsor's 95% confidence interval for the primary comparison runs from -3.07 to 3.07. Because it includes zero, the data are compatible with no difference under the analysis; because it also includes values on both sides of zero, it does not establish that the groups are equivalent.

How should the recalculation be understood?

The recalculated comparisons are simple, unadjusted calculations from the posted summary statistics. They are not substitutes for the trial's reported ANCOVA. For the primary endpoint, the recalculated mean difference is 0.0, with a confidence interval from -3.274 to 3.274 and p = 1.0. The recalculation uses an approximate standard deviation derived from the posted standard errors, as indicated in the analysis record. It does not reproduce any covariate adjustment that may have been used in the ANCOVA. In general, estimates from an adjusted analysis and an unadjusted summary-based calculation can differ because they use different information or assumptions.

What does a p-value mean?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be, if that null hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The primary sponsor-reported p-value is 0.998. This is consistent with the reported estimate being very close to zero under the stated analysis. It does not demonstrate that the treatments have identical effects, and it cannot compensate for the breadth of the confidence interval.

How do the planning illustrations differ from trial power?

The planning illustrations use the observed effect as a starting point and show hypothetical participants per arm for 80% or 90% power when planning for 100%, 75%, or 50% of that observed effect. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. These are planning scenarios, not observed power and not a report of the trial's original sample-size calculation. In general, planning around a smaller effect requires a larger sample to achieve a chosen power under otherwise similar assumptions. The trial's own sample-size justification is not reported in the registry record. Since the illustrations are based on the observed effect, they should not be read as independent confirmation of the effect's size.

11. Confidence Intervals and Precision

The sponsor-reported primary estimate is -0.003, with a 95% confidence interval from -3.07 to 3.07. The interval spans zero and extends in both directions, so the estimated result does not precisely identify either the direction or the magnitude of a between-group difference. The recalculated unadjusted interval runs from -3.274 to 3.274 around an estimate of 0.0. Both intervals communicate considerable uncertainty relative to the near-zero point estimates.

In general, a confidence interval is a range generated by a statistical procedure that, under its assumptions, is designed to cover the true parameter at the stated rate over repeated studies. It is not a range that assigns a probability to the true value after the data have been observed. The width of an interval reflects statistical precision: a wider interval leaves more possible values compatible with the data. The sponsor's primary interval is narrower than the recalculated interval, but both include zero and support the same broad caution against strong claims about the size or direction of a difference.

The registry does not report a clinically important difference for this endpoint. Without such a benchmark, the interval cannot be classified as excluding or including differences of clinical importance. The posted group standard errors, 1.23 for dapagliflozin and 1.13 for placebo, also indicate that the group estimates themselves are uncertain. The outcome counts listed for the primary analysis are 15 and 16, and the registry enrollment is 55; the relationship between those counts is not reported in the registry record.

The planning illustrations use the observed secondary effects to show hypothetical sample sizes under stated assumptions. They are not evidence that the current study had a particular probability of detecting an effect. A small p-value or a point estimate alone would not establish precision; interpretation should consider the confidence interval, the analysis used, and the limits of the record.

12. Analyses Reported by the Sponsor

The sponsor's primary analysis is an ANCOVA reported as a mean difference in final values. It gives an estimate of -0.003, a 95% confidence interval from -3.07 to 3.07, and p = 0.998. The posted adjusted-change estimates for dapagliflozin and placebo are each 0.28 umol/min/kg.

The recalculation is an unadjusted comparison based on the posted summary statistics. It gives a mean difference of 0.0, a 95% confidence interval from -3.274 to 3.274, and p = 1.0. It is not the same analysis as the ANCOVA: the recalculation does not incorporate any covariate adjustment, and its standard deviation is approximate. The two estimates and intervals differ slightly, but both centre near no difference and both include a broad range of values on either side of zero.

The sponsor-reported analysis is the appropriate reference for what the trial's own reported analysis concluded. The registry record does not provide the ANCOVA covariates or full model specification, limiting independent reconstruction. The close overall interpretation of the two comparisons should not be mistaken for identical methods, nor should the recalculation be used to replace the reported analysis.

13. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint and lists two secondary outcomes. The primary measure concerns skeletal muscle insulin-stimulated glucose uptake; the secondary measures concern adipose and liver uptake. Testing multiple outcomes creates a multiplicity issue: in general, the more comparisons assessed, the greater the chance that at least one result may appear notable by chance if each is interpreted without accounting for the others.

Whether a multiplicity adjustment, hierarchical testing strategy, or other prespecified approach was used is not reported in the registry record. The posted secondary p-values are unadjusted recalculations, and the record does not state how the sponsor intended to interpret the secondary analyses relative to the primary endpoint. Consequently, secondary findings should be treated cautiously rather than as equally definitive evidence.

The primary outcome population is described as the full analysis set. The registry lists outcome group counts of 15 for dapagliflozin and 16 for placebo, while enrollment is listed as 55. The safety record lists 16 participants at risk in each group. The relationship among these counts, the handling of missing outcome data, and the number of participants included in each reported analysis are not reported in the registry record. Reasons for any exclusions or unavailable measurements are also not reported in the registry record.

The registry record does not report the method used to handle missing data, whether analyses were conducted according to randomized assignment, or any sensitivity analyses for missingness. In general, missing-data assumptions can affect estimates if the observed participants differ from those whose outcomes are unavailable. Without details on the amount, pattern, and handling of missing data, the robustness of the estimates to missingness cannot be assessed from this record.

The stated full analysis set identifies the population label but does not, by itself, explain the exact inclusion rules. The record does not report a detailed statistical analysis plan, interim analyses, or sample-size justification. These omissions limit assessment of how completely the posted analyses follow a prespecified plan and how much weight to place on secondary results.

14. 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 safety record lists serious adverse events for 0 of 16 participants at risk in the dapagliflozin group and 0 of 16 participants at risk in the placebo group. It lists other adverse events for 6 of 16 participants at risk in the dapagliflozin group and 7 of 16 participants at risk in the placebo group. These are counts recorded during the study; they should be read in the context of the study's 8-week duration and the listed safety populations.

The absence of serious adverse events recorded in these groups does not establish that serious events cannot occur, particularly given the limited outcome counts and study period. The registry record does not provide a list of serious adverse event terms, and the deaths field is not reported in the registry record. It also does not provide event timing, severity details for the other adverse events, or a causal assessment for individual events.

These figures describe what the registry records for this study, not a complete assessment of safety across other settings or longer periods. They should not be interpreted as proof of safety or as evidence of a difference in risk between groups.

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

The posted primary result shows nearly identical adjusted-change estimates for the two groups and a sponsor-reported mean difference close to zero. Its confidence interval includes zero and a range of differences in both directions. The result therefore does not provide a precise estimate of the direction or size of any group difference in skeletal muscle insulin-stimulated glucose uptake over the study period.

This is not the same as demonstrating that the groups are equivalent. Equivalence requires a prespecified margin that defines what differences are small enough to count as equivalent, along with an analysis designed to assess that question. Such a margin and an equivalence analysis are not reported in the registry record. A non-significant result, or a p-value near one, is not proof that no difference exists.

The measured endpoint is a tissue-specific physiological measure. It does not directly report symptoms, daily functioning, complications, or long-term health outcomes. The registry describes an 8-week study, so the posted results do not establish what happens over a longer period. Nor do these results determine whether observed changes in tissue-specific uptake translate into outcomes that matter to patients.

The study record supports a bounded statistical conclusion: for the primary endpoint, the sponsor's analysis estimated a near-zero difference, but with uncertainty broad enough to include differences in either direction. The secondary outcomes also have uncertain estimates and do not provide a consistent pattern. The registry does not report the multiplicity strategy, missing-data methods, or covariates used in the ANCOVA, which further limits independent assessment.

These findings should not be translated into a recommendation about treatment. They describe the posted results from this trial and the precision of those estimates. They do not establish that dapagliflozin does or does not improve insulin sensitivity, and they do not resolve questions about clinical benefit, harm, or outcomes beyond the measures and time period recorded.

16. Why This Trial Matters Statistically

This trial is statistically informative because its primary estimate is close to zero while its confidence interval remains broad. That combination illustrates why a point estimate and a p-value are not enough to judge evidence. A near-zero estimate does not establish that all meaningful differences have been ruled out; the interval indicates that substantial uncertainty remains about the possible size and direction of the contrast.

The study also illustrates the distinction between the trial's reported adjusted analysis and a simple recalculation from group summaries. The sponsor's ANCOVA and the unadjusted recalculation lead to a similar broad reading, but they are not interchangeable. The registry does not report the model covariates, so a reader cannot fully reconstruct the sponsor analysis from the posted summaries. The recalculation is best treated as a transparent supplementary check, not as the definitive analysis.

The tissue-specific outcomes invite another statistical lesson: estimates from several related measures may point in different directions. Without a reported multiplicity strategy, secondary findings should not be treated as independent confirmation or as a basis for selecting a preferred narrative. Their uncertainty and their relationship to the primary endpoint matter.

Finally, the record distinguishes observed trial results from planning illustrations. Sample-size scenarios based on observed effects can help show how assumptions about a target effect influence planning, but they are not observed power and do not reveal the original design rationale. The trial's own sample-size justification is not reported in the registry record. Together, these points make the study useful for understanding precision, analysis choices, and the limits of registry reporting.

17. 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 primary outcome counts are 15 for dapagliflozin and 16 for placebo, while registry enrollment is 55. The safety record lists 16 participants at risk in each group. The registry record does not explain the relationship among these counts, the reasons for any differences, or whether all randomized participants contributed to each analysis. This makes the analysis populations difficult to reconcile from the record alone.

The primary ANCOVA is reported, but its covariates and detailed model specification are not. The recalculated comparison is unadjusted and relies on an approximate standard deviation derived from the posted standard errors. It can serve as a simple check, but it cannot reproduce an adjusted analysis without the underlying model details and participant-level data.

The registry record does not report the method for handling missing data, the extent or pattern of missing measurements, or sensitivity analyses. It also does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. The multiplicity approach for the two secondary endpoints is not reported in the registry record, which limits how confidently those results can be interpreted alongside the primary endpoint.

The study was conducted at a single centre and lasted 8 weeks. The primary and secondary endpoints are tissue-specific physiological measures, and longer-term clinical outcomes are not reported among the outcomes described. The record also does not report a clinically important difference for the primary measure, making it difficult to judge the practical importance of the confidence interval's possible values. These limitations constrain generalization and interpretation without changing the numerical results themselves.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effects of Dapagliflozin 10 mg on Insulin Resistance in Patients With Type 2 Diabetes Mellitus — NCT02426541.
• Registry record last updated 2018-02-05; status last verified 2017-07.
• Results first posted 2018-02-05.
• 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.

21. Record Summary

The registry describes a completed, single-centre, randomized, parallel-group, double-blind, placebo-controlled Phase IV study of dapagliflozin 10 mg once daily in people with Type 2 Diabetes Mellitus. The study lasted 8 weeks and compared dapagliflozin with matching placebo.

The primary endpoint was adjusted change from baseline to Week 8 in skeletal muscle insulin-stimulated glucose uptake. The sponsor-reported ANCOVA estimate was -0.003, with a 95% confidence interval from -3.07 to 3.07 and p = 0.998. The posted group estimates were both 0.28 umol/min/kg. The interval includes no difference and leaves substantial uncertainty about the possible size and direction of a difference.

The registry lists adipose and liver outcomes as secondary measures. Their estimates point in opposing directions, and both comparisons have confidence intervals that include no difference. The record does not report the multiplicity strategy, missing-data methods, ANCOVA covariates, or sample-size justification. These omissions, together with the limited outcome counts and study period, constrain interpretation to the posted physiological measures and their uncertainty.