Comparison of NN1250 Versus Insulin Glargine in Subjects With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of NN1250 Versus Insulin Glargine in Subjects With Type 2 Diabetes (NCT00982644), a randomized phase 3 study. The primary outcome is Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment.

2. Clinical Question

The central question is about a difference in average HbA1c change, not whether either group reached a particular target. The primary endpoint is expressed as change from baseline in percentage of glycosylated haemoglobin. The posted group means are both negative, indicating a reduction from baseline on average in each group; the registry comparison estimates the difference between those average changes.

The trial also followed consenting participants in an extension. Its stated purpose was to compare longer-term safety and tolerability, and the posted extension endpoint includes HbA1c change after 104 weeks. The record lists additional outcomes involving hypoglycaemic episodes and self-measured plasma glucose. These outcomes address different aspects of the comparison and should not be treated as interchangeable with the primary HbA1c result.

The main trial took place in Europe and the United States of America. The question therefore concerns participants meeting the trial’s entry criteria and treatment context, rather than every person with type 2 diabetes or every possible use of either insulin.

3. Trial Design

The registry describes a Phase 3, randomized, controlled, open-label, parallel-group, multicentre, multinational trial. It lists an enrollment of 1030. The main trial compared once-daily insulin degludec with once-daily insulin glargine over 52 weeks. The record describes the participants as people with type 2 diabetes who had not previously used insulin and qualified for more intensive treatment while taking oral anti-diabetic drugs.

The trial was open label, so masking was not used. The registry does not report details of the randomization procedure, allocation concealment, or any steps intended to reduce bias in outcome assessment. It identifies the design as parallel group and the allocation as randomized, but those labels alone do not establish how each procedural detail was handled.

Medication rules were not identical to simply continuing all existing oral drugs. When participants entered the main trial, oral anti-diabetic treatment was discontinued except for metformin and, in countries where its use with insulin was approved, a dipeptidyl peptidase-IV inhibitor. The record says that these rules applied to the main trial. The two insulin groups were otherwise described as receiving the assigned insulin once daily in combination with oral anti-diabetic drugs.

Participants who consented to the extension continued the treatment to which they had been randomly allocated during the main trial. The extension is registered separately within the official trial title and reports an endpoint at Week 104. The record does not give the number who consented to or completed the extension, so the extension results should not be read as evidence that every main-trial participant contributed data at that time.

The primary analysis population is described as the full analysis set, which included all randomized participants. Missing data for the primary endpoint were imputed using last observation carried forward. The registry record does not report the original sample-size justification, planned allocation ratio, detailed statistical analysis plan, or procedures for interim analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: All subjects who completed the 52-week main trial (NN51250-3579, NCT00982644) and when found to be eligible for the extension trial, were offered to participate in the 52-week extension trial (NN1250-3643). The total duration of treatment was up to 104 weeks (52 weeks + 52 weeks).

Main: Week 0 to 52 (NN1250-3579)

Reasons for not completing this period:

Extension: Week 53 to 104 (NN1250-3643)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF).

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 Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment, measured over Week 0, Week 52.

The primary endpoint is change in glycosylated haemoglobin (HbA1c) after 52 weeks of treatment, defined as change from baseline and measured in percentage of glycosylated haemoglobin. HbA1c is a continuous measure, so the registry reports a mean and standard deviation for each group. The primary analysis population is identified as the full analysis set, including all randomized participants, with missing observations imputed using last observation carried forward.

As a general statistical explanation, a change-from-baseline endpoint compares each participant’s measurement at follow-up with that participant’s starting measurement, then summarizes those changes across each group. Comparing mean changes can describe whether the groups’ average trajectories differed over the follow-up period. It does not by itself show how many participants experienced a particular change, how widely individual responses varied beyond the reported standard deviations, or whether a specific clinical target was reached.

HbA1c is used in this trial as a measure of glycaemic status over time. The endpoint is relevant to the stated comparison because both groups received insulin alongside oral anti-diabetic drugs and the study sought to compare efficacy over the main treatment period. The posted results show the group means and an estimated between-group mean difference. Interpretation should also account for the confidence interval, the handling of missing data, the open-label design, and the fact that the registry record does not report the complete statistical plan.

7. Results Posted in the Registry

• IGlar OD: mean -1.19 versus -1.06 on control; difference -0.13 (95% CI -0.27 to 0.01), standardized effect d = -0.13; z-test p = 0.065.

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.

Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment

• 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 deviations.
• Result:
  • IGlar OD: mean -1.11 versus -0.95 on control; difference -0.16 (95% CI -0.30 to -0.02), standardized effect d = -0.16; z-test p = 0.027.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for IGlar OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52

• 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 deviations.
• Result:
  • IGlar OD: mean 7.70 versus 7.70 on control; difference 0.00 (95% CI -0.30 to 0.30), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IGlar OD and the control. The interval gives the range of effects that remain compatible with the data.

Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104

• 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 deviations.
• Result:
  • IGlar OD: mean 7.60 versus 7.60 on control; difference 0.00 (95% CI -0.29 to 0.29), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IGlar OD and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover different aspects of the trial: mean change in HbA1c over the extension, self-measured plasma glucose profiles at the main-trial and extension time points, and rates of confirmed or nocturnal confirmed hypoglycaemic episodes. The posted numerical comparisons include HbA1c and the plasma glucose summaries; the registry lists the hypoglycaemia outcomes among its secondary endpoints but does not provide numerical results for them in the results represented by this record.

Across the posted continuous secondary outcomes, the arm means are close, and the glucose profile means are the same at the reported precision at each recorded time point. The extension HbA1c comparison has a confidence interval that excludes zero, unlike the primary Week 52 HbA1c comparison. These are distinct endpoint results and periods; their pattern does not change the definition or interpretation of the primary result.

Secondary endpoints can provide context, but they usually carry less confirmatory weight when the trial’s multiplicity plan is unknown. Testing several outcomes creates more opportunities for chance findings. A nominal, unadjusted p-value does not account for that broader set of comparisons. The registry record does not report a multiplicity procedure, a hierarchy among the secondary endpoints, or the full prespecified analysis plan.

The registry lists no reported analyses for the secondary results, and the posted comparisons are unadjusted. This means the record does not establish whether these were the analyses specified before the data were examined, whether other analyses were conducted, or how missing values were handled for each outcome. The secondary data can be described as posted, but they should not be treated as independent confirmation of the primary result or as a basis for broad claims about the comparative treatments.

The different endpoints also have different measurement scales and meanings. HbA1c summarizes one dimension of glycaemic status, self-measured plasma glucose profiles describe another, and episode rates concern event occurrence. Similarity in one outcome does not imply similarity in another, and a statistical contrast on one scale cannot be directly substituted for a result on another.

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

• Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
• Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment
• Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52
• Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104
• Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant has a numerical change in HbA1c, and the registry summarizes the groups using means and standard deviations. A mean is the arithmetic average of the observed or imputed changes in a group. A standard deviation describes how dispersed participant-level changes are around that group mean. Neither statistic alone tells the full shape of the outcome distribution.

What does the mean difference represent?

The mean difference is a contrast between the average changes in the randomized groups. The posted primary estimate is -0.13. Its sign depends on the ordering used for the comparison; the two arm means are reported separately as -1.06 for IDeg OD and -1.19 for IGlar OD. The estimate is the registry’s posted comparison, rather than a new calculation. A value near zero indicates that the estimated average changes were close relative to the scale of the outcome, while uncertainty around the estimate must be considered before drawing an interpretation.

As a general explanation, random assignment aims to make the groups comparable on average at the outset, including with respect to factors that are measured and factors that are not measured. It does not guarantee exact balance in any particular trial. The registry confirms randomization but does not give the randomization method, allocation concealment details, or baseline characteristics in the results presented for this endpoint.

How should the confidence interval be read?

A confidence interval describes statistical uncertainty around an estimated contrast under the assumptions of the analysis. The primary interval ranges from -0.268 to 0.008. Because it includes zero, the data do not pin down the direction of the mean difference with high precision: values on either side of zero remain compatible with the interval. The width also indicates that the estimate is not an exact value for the underlying contrast. The interval is not a range that contains every participant’s outcome, and it is not a guarantee that the true effect lies within those endpoints.

As a general explanation, a p-value measures how surprising data at least as inconsistent 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, and it does not measure the size or importance of a difference. The primary p-value is unadjusted and equals 0.065. The record does not report a full testing hierarchy, a multiplicity adjustment, or a specific threshold chosen in advance for interpreting this endpoint.

What does the analysis population and imputation mean?

The registry says the primary full analysis set included all randomized participants. It also says missing values were imputed using last observation carried forward. As a general explanation, this method uses a participant’s last recorded outcome as a substitute for an unavailable later outcome. It can retain participants in an analysis, but it assumes that carrying the last value forward is an appropriate representation of what would otherwise have been observed. That assumption may be unsuitable when outcomes change over time. The registry record does not report how many observations were missing, the reasons for missingness, or sensitivity analyses using other assumptions.

The posted arm counts for the primary outcome are 773 and 257. The record labels the full analysis set as all randomized participants, but does not explain the relationship between these posted counts and the imputation process in detail. The registry record does not report a per-protocol analysis or other alternative populations for the primary endpoint.

Why can over-dispersion matter?

As a general statistical explanation, over-dispersion means that observed variation is greater than a model expects. For a continuous endpoint, a large spread of participant changes relative to the mean contrast can make the contrast harder to estimate precisely. This is one reason group means should be interpreted alongside standard deviations and the confidence interval, rather than in isolation. The registry gives standard deviations for the primary endpoint but does not report a formal assessment of distributional assumptions or over-dispersion.

The reported comparison is a simple summary of the posted group-level statistics, not a substitute for a fully documented sponsor analysis. The registry record does not report adjustment for baseline covariates, site effects, country, or other factors, nor does it give details of the model used for the primary endpoint. It is therefore not possible to determine from the record whether the comparison came from an adjusted model or to reproduce all aspects of the original analysis.

For the extension HbA1c result and the posted self-measured plasma glucose results, the registry includes unadjusted comparisons, but lists no reported analyses for those endpoints. General statistical practice treats endpoint definitions, populations, missing-data methods, and multiplicity procedures as part of the analysis, not as details that can safely be inferred from a mean and confidence interval. The registry’s published information supports interpretation of the descriptive values and posted comparisons, but leaves those broader methodological details unreported.

11. Confidence Intervals and Precision

The primary mean difference is -0.13, and its confidence interval extends from -0.268 to 0.008. The interval includes zero and reaches slightly into positive values, so the data are compatible with a small difference in either direction as well as with no average difference. The estimate alone should not be treated as exact: the interval expresses the uncertainty associated with estimating a contrast from trial data.

The primary group standard deviations are 1.01 and 0.97. These describe participant-level variation, whereas the confidence interval describes uncertainty about the between-group mean difference. The distinction matters: a group can have considerable variation among participants while still permitting an estimate of its mean, and a mean difference can remain uncertain even when the reported group averages appear close.

The extension mean difference is -0.16, with an interval from -0.301 to -0.018. That interval lies below zero, but it belongs to a secondary endpoint and an extension period. Its statistical precision does not remove concerns about the unreported multiplicity plan or about which participants contributed extension data. The record does not report the extension analysis population or missing-data method in the same detail as the primary endpoint.

As a general explanation, an interval is narrower when the data and analysis yield a more precise estimate, and wider when uncertainty is greater. Its interpretation depends on the statistical model and assumptions used. The registry does not report the full model specification or sensitivity analyses, so the posted intervals cannot address uncertainty from every possible source, including the impact of missing-data assumptions or analytic choices.

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 describe participants per arm, not total events. The registry’s planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It sets the effect to detect as a stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the planned number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under those assumptions. The 90% power column uses a higher chance of detecting that effect and consequently gives a larger planning requirement. These are design calculations under a simplified scenario, not descriptions of the enrollment actually achieved in each arm.

Each row changes the assumed effect size relative to the observed effect. Planning for 75% of the observed effect means asking how many participants would be needed to detect an effect smaller than the observed one; planning for 50% means a still smaller target. Smaller effects are harder to distinguish from random variation and therefore require more participants, all else equal. The same logic explains why the higher power target calls for more participants than the lower target.

The planning figures are not observed power. They are illustrations based on the stated assumptions and the observed effect, not evidence that the completed trial had a particular probability of detecting a true effect. They should not be confused with the registry enrollment of 1030 or with the endpoint-specific analysis counts. The sample-size illustration also does not establish the assumptions that guided the original trial design, because those original assumptions are not reported.

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 = -0.130; pooled standard deviation σ = 1.000.
2. n = 2 × (1.96 + 0.842)² × 1.000² / -0.130² = 929.2, rounded up to 930 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 <- -0.13                      # observed difference in means
sigma <- 1.00018850363397                     # 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(982644)
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 = 930 (80% power), 1,244 (90% power)
 75% of observed effect: n per arm = 1,652 (80% power), 2,212 (90% power)
 50% of observed effect: n per arm = 3,717 (80% power), 4,976 (90% power)
power.t.test: 930.2 
Simulated power at n = 930 per arm: 0.797 (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. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the trial used a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for controlling the chance of false-positive findings across endpoints. This matters because the record lists multiple secondary outcomes in addition to the primary endpoint. When several statistical tests are considered, an unadjusted p-value for an individual endpoint does not account for the full set of comparisons.

The primary comparison is accompanied by an unadjusted p-value of 0.065. The extension HbA1c comparison has an unadjusted p-value of 0.027. These values should not be interpreted as if they came from a documented family-wise testing strategy: no such strategy is reported. The registry also lists no reported analyses for the secondary endpoint results, limiting the ability to assess whether the posted calculations match a prespecified analysis.

The primary population is described as the full analysis set, including all randomized participants, with missing data imputed by last observation carried forward. That information is useful, but incomplete for evaluating missing-data bias. The record does not state how many primary endpoint observations were missing, why they were missing, whether missingness differed between groups, or whether the imputation assumptions were assessed in sensitivity analyses. It does not report the detailed analysis population or missing-data approach for the extension and other secondary outcomes.

As a general statistical explanation, missing-data methods rely on assumptions about the unobserved outcomes. Carrying the last value forward may be convenient, but it treats a prior measurement as a stand-in for a later one and may not reflect the participant’s subsequent course. Alternative methods can produce different estimates, particularly when missingness is substantial or related to outcome. The registry does not provide enough information to evaluate that sensitivity.

The record also does not report the complete statistical analysis plan, the original sample-size justification, interim analyses, or details of the statistical model. These absences do not show that such planning or analyses did not occur; they mean that they are not reported in the registry record. The posted results therefore support a limited reading of the presented estimates rather than a full audit of the trial’s inferential procedures.

15. 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: coronary artery disease (1.3%), angina pectoris (0.8%), atrial fibrillation (0.8%), cardiac failure congestive (0.8%), coronary artery stenosis (0.8%).

The serious adverse event figures describe participants at risk and participants affected in each group. In the IDeg OD group, 766 participants were at risk and 116 were affected; in the IGlar OD group, 257 were at risk and 41 were affected. These are counts, not event rates adjusted for exposure time, and they do not indicate how many events each affected participant experienced.

The record lists coronary artery disease at 1.3% among the leading serious adverse event terms. Angina pectoris, atrial fibrillation, congestive cardiac failure, coronary artery stenosis, and myocardial infarction are each listed at 0.8%. These percentages describe the recorded terms; they are not a complete account of all possible safety outcomes or a direct comparison of risk between the randomized groups.

Deaths are not reported in the record’s adverse-event summary. The registry does not provide enough detail to assess event timing, duration of exposure, severity beyond the serious classification, or the statistical uncertainty around between-group safety differences. Serious adverse event counts should therefore be read as descriptive information, not as proof of a causal relationship or a definitive comparative safety conclusion.

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

The primary result describes the difference in average HbA1c change between the randomized groups at Week 52. The estimated mean difference is -0.13, and the confidence interval includes zero. This indicates that the posted data do not determine the direction of the average difference with high precision. It does not establish equivalence, because the registry does not report an equivalence margin or a non-inferiority margin.

The p-value of 0.065 is unadjusted. It should not be interpreted as the probability that the treatments are identical or as a measure of the clinical importance of the estimate. The registry record does not state what magnitude of HbA1c difference would be considered clinically important, so the reported numbers alone do not answer that question.

The trial’s randomized design supports a comparative interpretation, but the record’s open-label status, missing-data method, and incomplete reporting of the analysis plan are relevant context. The primary full analysis set used last observation carried forward for missing data. Without information about the amount and pattern of missingness or sensitivity analyses, the robustness of the primary estimate to alternative assumptions cannot be judged from the record.

The extension result is a separate secondary finding with a different follow-up period and a confidence interval that does not include zero. It does not overturn the primary result, and the record does not report a multiplicity strategy that would allow the secondary result to be interpreted as confirmatory. Likewise, outcomes such as glucose profiles and hypoglycaemic episodes address different questions and should not be collapsed into a single conclusion.

These results apply to the enrolled trial population and treatment context: people with type 2 diabetes who qualified for intensified treatment, had not previously used insulin, and followed the specified oral-drug rules. The findings do not automatically apply to other populations, treatment schedules, or circumstances. Statistical descriptions of these results are not medical advice and do not establish that either treatment works or fails to work.

17. Why This Trial Matters Statistically

This trial illustrates why a comparison of group means needs more than a glance at the estimates. The primary group means are -1.06 and -1.19, while the estimated between-group difference is -0.13. The confidence interval spans zero, making the uncertainty around the contrast central to interpretation. A difference in point estimates alone does not establish a clear separation between groups.

It also shows how a result can look different across follow-up periods and endpoints. The extension HbA1c estimate has a confidence interval that excludes zero, while the primary Week 52 interval includes zero. A secondary result can be informative, but its evidential weight depends on whether it was prespecified, how many outcomes were examined, and how missing data and multiplicity were handled. Those details are not reported in the registry record.

The trial provides a practical example of why analysis population and imputation rules matter. The primary analysis used the full analysis set and last observation carried forward. Those choices affect which data contribute and how absent follow-up values are represented. Without reporting the amount of missing data and sensitivity analyses, readers cannot fully judge how dependent the estimate is on that method.

Finally, the record distinguishes a trial’s observed results from planning calculations. The sample-size illustration is based on the observed effect under stated assumptions, whereas the original design justification is not reported. Keeping those purposes separate helps prevent a retrospective planning scenario from being mistaken for evidence about the trial’s original design or its observed power.

18. 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 description leaves important design and analysis details unreported. It identifies the study as randomized and open label, but does not describe the randomization procedure, allocation concealment, outcome-assessment safeguards, or the full statistical model. These omissions make it difficult to evaluate the methods beyond the information recorded.

For the primary endpoint, the full analysis set included all randomized participants and missing data were imputed using last observation carried forward. The number of missing measurements, reasons for missingness, and sensitivity analyses are not reported. The extension analysis population and its missing-data approach are also not described in comparable detail. The extension results may therefore reflect a subset of main-trial participants, but the record does not state the extent or implications of that selection.

The registry does not report the original sample-size justification or a complete statistical analysis plan. It also does not report multiplicity control, interim analyses, or a prespecified hierarchy for the numerous secondary outcomes. The posted unadjusted secondary comparisons should consequently be interpreted cautiously, and the presence of a nominally notable result does not establish that it was confirmatory.

The main trial’s oral-drug rules varied according to whether a DPP-IV inhibitor was approved for combination treatment with insulin in a participant’s country. This is part of the recorded treatment context and may limit how readily the trial can be generalized to settings with different medication practices. The open-label design is another consideration, particularly for outcomes that involve participant reporting or clinical decisions; the record does not describe measures used to address this.

The adverse-event summary gives counts and leading serious event terms, but does not provide a full account of exposure-adjusted rates, event timing, or comparative uncertainty. Deaths are not reported. These limitations mean the safety figures are descriptive and cannot support a definitive comparative safety assessment on their own.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparison of NN1250 Versus Insulin Glargine in Subjects With Type 2 Diabetes — NCT00982644.
• Registry record last updated 2017-02-09; status last verified 2016-12.
• Results first posted 2015-11-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry record describes a Phase 3 randomized, controlled, open-label, parallel-group trial of once-daily insulin degludec and insulin glargine in people with type 2 diabetes. The main trial lasted 52 weeks, with a registered extension reporting outcomes at Week 104. Enrollment was 1030, and the trial took place in Europe and the United States.

The primary endpoint was change in HbA1c after 52 weeks. The posted mean difference was -0.13, with a confidence interval spanning zero and an unadjusted p-value of 0.065. The primary analysis used the full analysis set and last observation carried forward for missing data. The registry also posts extension and other secondary results, but does not report a complete analysis plan or multiplicity procedure.

Serious adverse event counts and selected event terms are recorded, while deaths are not reported in the adverse-event summary. The original sample-size justification, detailed randomization procedures, interim analyses, and several missing-data and analysis details are not reported in the registry record.