Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone (NCT00641043), a randomized phase 3 study. The primary outcome is HbA1c Change From Baseline to Week 24.

2. Clinical Question

The clinical question is framed around an additional medicine in a two-drug regimen. Because the comparator also received pioglitazone, the endpoint contrast describes the groups’ HbA1c changes under those two assigned combinations. It does not estimate the effect of pioglitazone alone, or compare either combination with a different background treatment. The record states that participants had type 2 diabetes with insufficient glycaemic control and could be drug naive or previously treated. It does not report further eligibility details in the registry record.

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group, placebo-controlled study. It compared oral linagliptin (BI 1356) 5 mg once daily plus pioglitazone 30 mg once daily with matching placebo plus pioglitazone 30 mg once daily. The stated study duration was 24 weeks. The registry lists an enrollment of 389 and describes the study as completed.

The intended population was people with type 2 diabetes and insufficient glycaemic control who were drug naive or previously treated. The primary analysis was defined as the Full Analysis Set: treated and randomized patients with baseline and at least one on-treatment HbA1c measurement. Last observation carried forward was used for imputation. The arm counts reported for the primary outcome are 128 for placebo plus pioglitazone and 252 for linagliptin plus pioglitazone. These are outcome-analysis counts and should not be treated as a replacement for the registry’s enrollment figure.

The primary endpoint was HbA1c change from baseline to week 24. Secondary outcomes listed in the record include HbA1c changes at earlier weeks, fasting plasma glucose changes, and the percentage of patients with HbA1c <7.0% at week 24. The registry record does not report the randomization procedure, allocation ratio as a protocol feature, or further operational details of masking. The original sample-size justification and the trial’s prespecified statistical plan 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: The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

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.

6. Primary Endpoint

The registry lists the primary outcome as HbA1c Change From Baseline to Week 24, measured over Baseline and week 24.

The primary endpoint was change in HbA1c from baseline to week 24, measured as a percentage. HbA1c reflects glycated haemoglobin; the outcome description defines change as the week 24 HbA1c percentage minus the baseline HbA1c percentage. A negative change therefore represents a lower measured value at week 24 than at baseline, without by itself establishing why that change occurred.

The registry reports treatment-adjusted means accounting for baseline HbA1c and previous anti-diabetic medication. The reported contrast is between the adjusted mean changes in the two randomized groups. This makes the endpoint a continuous measure: it retains information about the magnitude of change rather than reducing the outcome to whether a participant did or did not cross a threshold. The record also lists the percentage of patients reaching HbA1c <7.0% as a secondary outcome, but that threshold is not the primary endpoint.

HbA1c is used in this trial as a measure of glycaemic control. Comparing change from baseline can describe how the groups’ measured values shifted during the 24-week study. Interpretation should remain tied to the stated population, treatment combinations, measurement period, adjustment, and imputation approach. The registry record does not provide additional details about measurement procedures or the clinical rationale used to select the endpoint.

7. Results Posted in the Registry

• Linagliptin + Pioglitazone: mean -1.06 versus -0.56 on control; difference -0.50 (95% CI -0.71 to -0.29), standardized effect d = -0.51; z-test p = <0.001.

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.

HbA1c Change From Baseline to Week 6

• 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:
  • Linagliptin + Pioglitazone: mean -0.41 versus -0.03 on control; difference -0.38 (95% CI -0.52 to -0.24), standardized effect d = -0.58; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Linagliptin + Pioglitazone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

HbA1c Change From Baseline to Week 12

• 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:
  • Linagliptin + Pioglitazone: mean -0.85 versus -0.35 on control; difference -0.50 (95% CI -0.67 to -0.33), standardized effect d = -0.63; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Linagliptin + Pioglitazone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

HbA1c Change From Baseline to Week 18

• 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:
  • Linagliptin + Pioglitazone: mean -1.06 versus -0.55 on control; difference -0.51 (95% CI -0.71 to -0.31), standardized effect d = -0.54; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Linagliptin + Pioglitazone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering HbA1c change at weeks 6, 12, and 18, fasting plasma glucose changes at several time points, and the percentage of patients with HbA1c <7.0% at week 24. The numerical secondary results available in this record include the three earlier HbA1c comparisons. Across those reported time points, the mean changes and the ANCOVA comparisons are directionally consistent with the primary week 24 result: the linagliptin-plus-pioglitazone group has more negative mean HbA1c changes than the placebo-plus-pioglitazone group.

These secondary outcomes provide context for the primary result by describing HbA1c at earlier study visits and naming other glycaemic measures of interest. They do not replace the week 24 primary endpoint, and findings across outcomes should not be treated as independent confirmations. The registry lists 12 posted secondary outcomes and 11 analyses, but numerical results for the other listed secondary measures are not reported in the registry record.

The reported secondary ANCOVA p-values are all < 0.001 for the available HbA1c comparisons. However, the registry record does not report whether the secondary hypotheses were prespecified in a hierarchy or whether any multiplicity adjustment was applied. In general, testing multiple outcomes or time points increases the chance of obtaining small p-values by chance if no adjustment is made. For that reason, unadjusted secondary results carry less weight than a clearly specified primary analysis, especially when the testing plan is not available. The secondary pattern is descriptive support for the primary comparison, not a basis for stronger claims than the reported design and analysis permit.

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

• HbA1c Change From Baseline to Week 6
• HbA1c Change From Baseline to Week 12
• HbA1c Change From Baseline to Week 18
• FPG Change From Baseline to Week 24
• FPG Change From Baseline to Week 6
• FPG Change From Baseline to Week 12
• FPG Change From Baseline to Week 18
• Percentage of Patients With HbA1c <7.0% at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous variable: mean change in HbA1c from baseline to week 24. The registry reports treatment-adjusted means with standard errors for each group. A standard error describes the uncertainty in an estimated mean; it is not the same quantity as the spread of individual measurements. The primary outcome description states that adjustment was made for baseline HbA1c and previous anti-diabetic medication.

What does the reported ANCOVA estimate represent?

The sponsor’s primary analysis used ANCOVA and reported a mean difference in final values. ANCOVA is a general statistical method for comparing groups while accounting for specified covariates. In this record, the endpoint description identifies baseline HbA1c and previous anti-diabetic medication as adjustment factors for the treatment-adjusted means. The resulting estimate is the sponsor’s adjusted comparison, rather than a direct subtraction of the two posted arm means. The registry record does not provide further model details, such as the precise model specification or diagnostics.

The sponsor reported an estimate of -0.51, a 95% confidence interval from -0.71 to -0.30, and p < 0.001. The recalculated estimate of -0.5 and its 95% confidence interval from -0.712 to -0.288 are unadjusted calculations based on posted summary statistics. Because the recalculation does not reproduce the sponsor’s covariate-adjusted model, small differences between the estimates and interval limits are expected as a general consequence of using different methods and reported rounding. The registry marks no discrepancy between the calculations.

How should the change score be read?

The outcome is defined as week 24 HbA1c percentage minus baseline HbA1c percentage. Thus a negative group mean indicates a mean decrease over that interval. The between-group contrast compares those changes. It is not a comparison of the absolute baseline values, nor does it show the distribution of individual changes. Means can be useful for a continuous outcome because they use the measured scale, but they can also conceal variation among participants. The registry provides standard errors for the means, not the individual-level distributions in the registry record for this analysis.

What does a p-value tell the reader?

In general, a p-value describes how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions held. It is not the probability that the null hypothesis is true, a measure of the size of the effect, or a measure of its clinical importance. The sponsor’s p-value is tied to its ANCOVA analysis; the recalculated p-value is explicitly unadjusted. The registry record does not report additional details about the test specification or whether the primary analysis was part of a broader testing hierarchy.

What role does imputation play?

The Full Analysis Set included treated and randomized participants with baseline and at least one on-treatment HbA1c measurement. The record says that last observation carried forward was used as the imputation rule. In general, LOCF fills a later missing measurement with the participant’s last observed value. This defines how some incomplete outcome records enter the analysis, but it does not reveal why data were missing or whether the imputed values resemble the unobserved values. Alternative missing-data methods and sensitivity analyses are not reported in the registry record.

Randomization and double masking are features of the stated design that support a structured comparison between groups. General statistical interpretation still depends on how the study was conducted, which participants entered each analysis, and the assumptions of the model. The registry record does not report the detailed allocation method, ANCOVA diagnostics, or a complete statistical analysis plan. These absent details should not be inferred from the reported estimate alone.

11. Confidence Intervals and Precision

For the primary endpoint, the sponsor’s ANCOVA estimate was -0.51, with a 95% confidence interval from -0.71 to -0.30. The simple unadjusted recalculation was -0.5, with a 95% confidence interval from -0.712 to -0.288. Both intervals are entirely below zero, and each conveys uncertainty around its own estimate under its own analysis. The sponsor’s interval is based on the reported ANCOVA; the recalculated interval is based on posted summary statistics.

In general, a confidence interval is a range generated by a statistical procedure that, under its assumptions, has a stated long-run coverage rate. A narrower interval indicates greater precision for that estimate under the model; a wider interval indicates more uncertainty. It is not a range of individual participant outcomes, and it does not account for every possible source of uncertainty, such as limitations in the study design or unreported analysis choices.

The reported estimates are similar in direction and magnitude, but the intervals should not be treated as interchangeable. The sponsor’s estimate is adjusted as described for baseline HbA1c and previous anti-diabetic medication; the recalculated result is unadjusted. The registry record does not provide additional uncertainty analyses or sensitivity analyses for the primary result. Precision in the reported interval therefore does not resolve questions about missing-data assumptions, generalizability, or clinical importance.

The standard errors accompanying the arm means are measures of uncertainty in the estimated means, not standard deviations describing participant-to-participant variability. The registry does not provide enough information in the registry record to characterize the full outcome distribution. Confidence intervals support an assessment of statistical precision, but they do not, on their own, determine whether the observed contrast matters in a broader clinical context.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. The endpoint is continuous, so the illustration concerns participant counts in each of two groups. It uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. These are planning assumptions for an illustration; the original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a design that would have an 80% chance of detecting the chosen effect under the stated assumptions if that effect were the true one. The 90% power column gives the corresponding planning count for a 90% chance. These are design probabilities under a model, not guarantees about what a future study will find. For this primary endpoint, the illustration gives 60 participants per arm for planning for 100% of the observed effect and 80 per arm for 90% power at that effect. Planning for 75% of the observed effect gives 107 per arm for 80% power and 143 per arm for 90% power. Planning for 50% gives 239 per arm for 80% power and 320 per arm for 90% power.

Smaller effects require more participants to detect under the same assumptions. The curve is read as a planning illustration of how the required count changes with the effect being targeted; it does not show the study’s observed enrollment or its actual chance of success. These figures are not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.500; pooled standard deviation σ = 0.975.
2. n = 2 × (1.96 + 0.842)² × 0.975² / -0.500² = 59.7, rounded up to 60 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.5                      # observed difference in means
sigma <- 0.975060437687253                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(641043)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 60 (80% power), 80 (90% power)
 75% of observed effect: n per arm = 107 (80% power), 143 (90% power)
 50% of observed effect: n per arm = 239 (80% power), 320 (90% power)
power.t.test: 60.7 
Simulated power at n = 60 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s primary analysis was ANCOVA, with a reported mean difference of -0.51, a 95% confidence interval from -0.71 to -0.30, and p < 0.001. The endpoint description says that treatment-adjusted means account for baseline HbA1c and previous anti-diabetic medication. This is the trial’s own reported analysis and is the main inferential result recorded for the primary endpoint.

The recalculated result is a simple unadjusted comparison from the posted summary statistics: -0.5, with a 95% confidence interval from -0.712 to -0.288 and p <0.001. It is useful as a check on the direction and approximate size of the contrast, but it does not recreate the sponsor’s covariate-adjusted ANCOVA. The confidence limits and p-values also reflect their different methods and the precision with which the results are reported.

The registry indicates no discrepancy between the reported and recalculated results. The estimates are close, and both intervals lie below zero, but the sponsor analysis remains the appropriate result to cite as the study’s reported analysis. The recalculation should be understood as a secondary, unadjusted check rather than as a replacement for the sponsor’s model.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and lists secondary outcomes, but it does not report a multiplicity-adjustment procedure or a testing hierarchy. It is therefore not possible to determine from the record whether the secondary p-values were adjusted to account for testing several outcomes or time points. In general, multiplicity matters because a larger family of statistical tests can increase the chance of at least one apparently unusual result even when there is no underlying group difference. The reported secondary results should be interpreted with that limitation in mind.

The record reports 13 outcome measures and 11 analyses. It names secondary HbA1c changes, fasting plasma glucose changes, and the percentage reaching HbA1c <7.0% at week 24. Numeric results for some listed secondary measures are not reported in the registry record. The prespecified analysis plan, including any rules for handling multiple endpoints, is not reported in the registry record.

The Full Analysis Set was defined as treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. LOCF was used as the imputation rule. In general, the treatment of missing outcome data can affect estimates, and LOCF makes a specific assumption by carrying forward a participant’s last observed value. The record does not explain the reasons for missing measurements, describe the extent or pattern of missingness, or report sensitivity analyses using alternative assumptions.

The registry record also does not report interim analyses, the original sample-size justification, or the trial’s full statistical plan. These omissions limit assessment of whether the reported analyses followed a prospectively specified strategy. They do not negate the reported result, but they set boundaries on what can be concluded about robustness and the interpretation of secondary findings.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: glaucoma (0.8%), cholecystitis acute (0.8%), cholelithiasis (0.8%), tendonitis (0.8%), acute coronary syndrome (0.4%).

For serious adverse events, the registry reports 3 affected participants among 130 at risk in the placebo-plus-pioglitazone group and 8 among 259 at risk in the linagliptin-plus-pioglitazone group. These are counts of participants with serious adverse events and the corresponding numbers at risk, not measures of whether an event was caused by a study treatment. The registry does not provide a causal attribution in the registry record.

The record lists glaucoma, acute cholecystitis, cholelithiasis, and tendonitis at 0.8% each, and acute coronary syndrome and upper abdominal pain at 0.4% each among the top serious-event terms. The listed percentages are not assigned to an arm in the available details, so they should not be used to compare groups. Death counts are not reported in the registry record.

These summaries provide a limited account of recorded serious events. They do not by themselves establish comparative safety, explain the clinical circumstances of events, or show the full range of adverse events. The registry also reports other adverse-event counts, but an interpretation of safety should consider the definitions, follow-up, and event detail available in the record.

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

The primary result describes a difference in mean HbA1c change between two assigned combinations over 24 weeks in a phase 3 randomized, double-blind study. The sponsor’s ANCOVA estimate was -0.51, with a 95% confidence interval from -0.71 to -0.30. The result is a group comparison, adjusted as described in the registry, and not a prediction of an individual participant’s outcome.

The comparison is specifically linagliptin plus pioglitazone versus placebo plus pioglitazone. It does not isolate the effect of pioglitazone, compare either treatment with no therapy, or establish how the combinations compare with regimens not studied in this trial. The study population was people with type 2 diabetes and insufficient glycaemic control who were drug naive or previously treated. The findings should not be extended automatically to populations or treatment settings not represented in the registry record.

The interval and p-value describe statistical evidence and precision under the reported analysis. They do not establish clinical importance, long-term effects, or effects on outcomes not measured as the primary endpoint. The 24-week study duration also limits what can be said about results beyond that period. The registry record does not report the original sample-size rationale, a full analysis plan, or sensitivity analyses for missing data.

Safety counts are descriptive and do not establish that an event was caused by a treatment. Likewise, the secondary results require caution because the registry does not report how multiple comparisons were handled. The findings describe what the posted results report for this trial; they are not medical advice or a recommendation about treatment.

18. Why This Trial Matters Statistically

This trial offers a clear randomized comparison of adding linagliptin or matching placebo to the same pioglitazone regimen. That structure makes the primary contrast relevant to the incremental comparison defined by the study, rather than a comparison between different background therapies. The primary endpoint is a continuous measure, and the registry supplies both group means and the sponsor’s adjusted comparison.

The record also illustrates why different analyses of the same endpoint should be distinguished. The recalculated unadjusted contrast is close to the sponsor’s ANCOVA estimate, but the sponsor’s analysis accounts for baseline HbA1c and previous anti-diabetic medication as described in the endpoint record. Reporting both makes the role of adjustment visible and helps readers understand why an unadjusted check is not a substitute for the trial’s own model.

Several interpretive limits remain important. The registry provides a specific Full Analysis Set and LOCF rule, but not sensitivity analyses that would show how estimates behave under other missing-data assumptions. It lists multiple secondary outcomes but does not report a multiplicity plan. Nor does it report the original sample-size justification or the full statistical analysis plan. These gaps affect how confidently readers can assess robustness and secondary findings.

For biostatistical interpretation, the trial therefore brings together a defined design, a primary continuous endpoint, an adjusted sponsor estimate, and a transparent unadjusted recalculation, while also showing the boundaries imposed by incomplete reporting. Keeping those distinctions explicit supports a careful reading of both the estimated contrast and the evidence around it.

19. 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 registry does not report the original sample-size justification or the assumptions used when the trial was designed. The planning illustration based on the observed effect cannot fill that gap. The full statistical analysis plan is also not reported, including details about the model specification beyond the named ANCOVA and the stated adjustment for baseline HbA1c and previous anti-diabetic medication.

The primary analysis uses LOCF for imputation, but the registry record does not describe the amount or pattern of missing data, why measurements were missing, or sensitivity analyses using alternative methods. As a result, the impact of the imputation assumption cannot be assessed from the reported information. The Full Analysis Set definition is available, but the record does not provide further detail on participants excluded from that analysis or reasons for exclusion.

The record lists multiple secondary outcomes and reports several secondary HbA1c analyses, but it does not report a multiplicity strategy. Numeric results for the listed fasting plasma glucose and HbA1c threshold outcomes are not reported in the registry record. The secondary evidence therefore cannot be assessed comprehensively from the numerical results.

The trial’s stated follow-up was 24 weeks. The registry record does not support conclusions about longer-term outcomes. Serious adverse-event counts and selected event terms are reported, but the detailed circumstances and causal assessments are not available in the registry record. These limitations concern the amount of information available for interpretation; they do not change the reported estimates.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone — NCT00641043.
• Registry record last updated 2014-02-17; status last verified 2014-01.
• Results first posted 2011-06-07.
• 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.

23. Record Summary

The registry record describes a completed phase 3 randomized, double-blind, parallel-group, placebo-controlled study with enrollment of 389. It compared linagliptin (BI 1356) 5 mg once daily plus pioglitazone 30 mg once daily with matching placebo plus pioglitazone 30 mg once daily over 24 weeks in people with type 2 diabetes and insufficient glycaemic control.

The primary endpoint was HbA1c change from baseline to week 24. The sponsor reported an ANCOVA mean difference of -0.51, with a 95% confidence interval from -0.71 to -0.30 and p < 0.001. The analysis population was the Full Analysis Set as defined in the registry, with LOCF used for imputation. The record also lists secondary glycaemic outcomes and adverse-event summaries, while important details about multiplicity, the original sample-size rationale, and sensitivity analyses are not reported in the registry record.