Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes (NCT00972283), 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 statistical comparison is between the mean changes in HbA1c for the two randomized groups. The outcome is continuous, so the registry reports group means and standard deviations, along with a mean difference and an interval estimate. The main estimate is expressed as the insulin glargine group minus the insulin degludec group. Its direction therefore needs to be read in relation to that ordering: a negative difference means the reported mean change was more negative in the insulin glargine group.

The clinical question is not answered by a p-value alone. The estimated size and precision of the between-group difference also matter, as do the analysis population, missing-data approach, and whether other outcomes were examined. The registry record does not report a prespecified threshold for a clinically important difference or a detailed statistical analysis plan, so the statistical results cannot establish how large a difference would be clinically meaningful.

3. Trial Design

The registry describes a phase 3, randomized, parallel-group, open-label trial with an enrollment of 1006. The main period was planned for 52 weeks and compared insulin degludec with insulin glargine, with insulin aspart used as mealtime insulin in the basal-bolus regimens. The trial was multicentre and multinational. Its status is recorded as completed, and the registry lists a start date of 2009-09-01 and a primary completion date of 2010-10-28.

The brief description says that oral anti-diabetic drug treatment was discontinued at entry, if applicable, except for metformin and pioglitazone. The official title and brief description specify that these drugs could be used with or without the insulin regimens. The registry does not give further arm-level detail about medication use or treatment titration in the results record.

The primary endpoint analysis population was the full analysis set, described as including all randomized participants. The endpoint description also says missing data were imputed using last observation carried forward. For this outcome, the registry reports 744 participants in the insulin degludec group and 248 in the insulin glargine group. These are the group counts attached to the primary endpoint results; they should not be confused with the total enrollment.

The registry also describes an extension trial. Participants who consented to enter it continued the treatment to which they had been randomly allocated in the 52-week trial. Extension outcomes include HbA1c change and a nine-point self-measured plasma glucose profile at week 78. The registry record does not report the number who consented to the extension or detailed information about their follow-up.

Randomization can support a fair comparison of groups at the start of a trial, while open-label treatment means participants and study personnel were not masked to assignment. The registry does not report the randomization procedure, allocation concealment, masking of outcome assessors, or the original sample-size justification. It also does not report interim analyses or a detailed protocol-level statistical plan.

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 (NN1250-3582, NCT00972283) and were found to be eligible for the extension trial were offered to participate in the 26-week extension trial (NN1250-3667). The total duration of treatment was up to 78 weeks (52 weeks + 26 weeks).

Main: Week 0 to 52 (NN1250-3582)

Reasons for not completing this period:

Extension: Week 53 to 78 (NN1250-3667)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 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, or HbA1c, from baseline to week 52. It is measured as a percentage of glycosylated haemoglobin, and the registry summarizes the outcome as a mean with a standard deviation. Change is calculated relative to the baseline measurement, so a negative group mean indicates a decrease from baseline on the reported scale.

HbA1c is used as a continuous measure of longer-term glycaemic exposure. In general, measuring change from baseline allows a trial to describe how the outcome shifted during the treatment period, while comparing changes between randomized groups focuses on the difference in those shifts. This is a general explanation of the measure; the registry record does not state a threshold for a clinically important change.

The endpoint description identifies the full analysis set as the population and says missing data were handled using last observation carried forward. That approach uses an earlier observed value when a later measurement is missing. As a general statistical matter, this can affect the estimated group means, particularly if missingness is related to the outcome or if the outcome changes over time. The registry record does not report the amount or pattern of missing primary endpoint data, or sensitivity analyses using other missing-data assumptions.

The primary endpoint is distinct from the secondary glucose-profile and safety outcomes. A result for one measure does not, by itself, settle what the other outcomes indicate, and the registry record does not state how the outcomes were prioritized in a complete statistical analysis plan.

7. Results Posted in the Registry

• IGlar OD: mean -1.29 versus -1.17 on control; difference -0.12 (95% CI -0.26 to 0.02), standardized effect d = -0.12; z-test p = 0.099.

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 78 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 -1.15 versus -0.95 on control; difference -0.20 (95% CI -0.35 to -0.05), standardized effect d = -0.18; z-test p = 0.008.
• 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 6.90 versus 7.30 on control; difference -0.40 (95% CI -0.63 to -0.17), standardized effect d = -0.23; z-test p = <0.001.
• 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.

Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 78

• 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 6.80 versus 7.20 on control; difference -0.40 (95% CI -0.63 to -0.17), standardized effect d = -0.22; z-test p = <0.001.
• 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.

The posted secondary outcomes broadly point in a consistent direction across the continuous measures: mean change in HbA1c at week 78 is more negative in the insulin glargine group, and mean nine-point self-measured plasma glucose is lower in that group at both the main-trial and extension timepoints. The corresponding unadjusted comparisons are reported with intervals that do not cross zero. This pattern provides additional descriptive context alongside the primary result, whose interval does cross zero.

The secondary outcomes are not interchangeable with the primary endpoint. HbA1c and a plasma glucose profile measure different aspects of glycaemic outcomes, and results at week 78 concern the extension period rather than the main 52-week endpoint. The registry does not report the extension participation count, detailed missing-data handling for the secondary outcomes, or a complete analysis plan. These omissions limit direct comparisons across timepoints and outcomes.

The registry also lists confirmed hypoglycaemic episodes and nocturnal confirmed hypoglycaemic episodes among secondary outcomes, but numeric results for these outcomes are not reported in the registry record. Their inclusion in the outcome list is not evidence of a particular result.

Unadjusted secondary results carry less weight as confirmatory evidence when several outcomes are assessed. As a general statistical principle, testing more outcomes can increase the chance of at least one small p-value even when there is no underlying difference for those outcomes. The registry record does not report a multiplicity strategy or identify a testing hierarchy. The secondary findings are therefore best read as supporting descriptions of the posted pattern, rather than as independent proof that resolves the primary comparison.

None of these results establishes the clinical importance of the differences. The record does not give a threshold for meaningful change, and statistical evidence about an average difference does not describe all individual outcomes. The secondary results complement, but do not replace, the primary comparison and its uncertainty.

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

• Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 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 78
• Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
• Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a mean change for each group. The central comparison is a difference between means. The reported contrast is ordered as insulin glargine minus insulin degludec: the group means are -1.29 and -1.17, respectively, and the contrast is -0.12. The minus sign indicates that the mean change in the insulin glargine group was more negative by the reported contrast. This sign describes the arithmetic direction only; it does not, by itself, determine clinical importance.

What does a mean difference describe?

A mean difference compares group averages on the original measurement scale. It does not imply that every participant had the same change or that the average captures the full spread of individual outcomes. The registry gives standard deviations of 1.03 and 0.98 for the primary outcome. In general, a standard deviation describes how dispersed individual observations are around a group mean. It is not the same as the standard error, which describes uncertainty in an estimated mean.

The two primary endpoint groups have different reported sizes: 744 and 248. A comparison with unequal group sizes can have different precision contributions from each group. The registry's posted primary comparison includes an interval estimate and an unadjusted p-value. It does not describe the complete model, any covariate adjustment, or whether the posted contrast is from the sponsor's prespecified analysis. The record lists no reported analyses.

How should the p-value be read?

A p-value measures how unusual data at least as extreme as the observed result would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not quantify the probability that a treatment effect is real. The primary p-value is 0.099. The registry labels the comparison unadjusted; the record does not describe the full model or any adjustment. General convention often uses a threshold such as 0.05, but a threshold cannot replace consideration of the estimated effect and its uncertainty.

The p-values reported for the secondary outcomes are also unadjusted. In general, when many outcome comparisons are made, the chance of finding one with a small p-value by chance increases. Methods such as prespecifying a hierarchy or adjusting for multiple comparisons can address this issue, but the registry record does not report whether such a plan existed or was used. The secondary results therefore should not be treated as if they were a single confirmatory test.

What does an interval estimate add?

An interval estimate gives a range of values compatible with the data under the method used. In general, narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. For the primary endpoint, the reported interval extends from -0.263 to 0.023 and includes zero. The confidence level and exact method used to construct the interval are not reported in the registry record, so no particular confidence level should be assumed from the registry alone.

For the week-78 HbA1c comparison, the reported interval is -0.348 to -0.052, and the unadjusted p-value is 0.008. The intervals for the week-52 and week-78 glucose profiles are reported as -0.631 to -0.169 and -0.625 to -0.175, respectively, with p-values of <0.001. These are registry-posted summary comparisons; the record does not list reported analyses explaining any model or adjustment behind them.

Why can over-dispersion matter?

Over-dispersion is a general concern when variability in the data is greater than a model assumes. If a method understates variability, standard errors can be too small and intervals too narrow; if it accounts for extra variability appropriately, uncertainty estimates can be more realistic. This concept is especially relevant to count or event-rate outcomes. The primary endpoint is continuous, and the registry record does not report an over-dispersion assessment or model for it. The general principle should not be taken as a claim that over-dispersion was present in this trial.

The secondary outcomes include rates of confirmed and nocturnal confirmed hypoglycaemic episodes in the registry's outcome list, but the posted numeric secondary results described in the record do not include those rates. The record does not report the analyses or estimates for these listed safety outcomes. No conclusions about their comparative rates can be drawn from the posted numeric results.

11. Confidence Intervals and Precision

Precision is conveyed principally by the interval around an estimated difference. For the week-52 primary HbA1c comparison, the estimate is -0.12, and the reported interval runs from -0.263 to 0.023. Because the interval crosses zero, it includes both a negative contrast and values on the other side of zero. The result therefore leaves uncertainty about the direction and size of the between-group difference. It is not evidence that the true difference is exactly zero.

The registry record does not report the confidence level of the interval or the method used to construct it. Accordingly, the interval can be described as an interval estimate, but should not be assigned a specific confidence level based on the registry record alone. The p-value is 0.099 and is described as unadjusted; it is a separate summary of the data under a null model, not a substitute for the interval.

The primary groups have different sample sizes, and the reported standard deviations describe substantial variation around each group mean. In general, more observations can improve precision, but precision also depends on variability, the analysis method, and the balance between groups. The registry's group counts and standard deviations help put the estimate in context, but do not remove uncertainty.

The week-78 HbA1c interval lies below zero, while the intervals for the two glucose-profile comparisons also lie below zero. Their reported unadjusted p-values are 0.008 and <0.001, respectively. These interval patterns are descriptive of the posted secondary estimates; multiplicity and unreported analysis details limit how strongly they should be interpreted. Precision alone does not establish clinical importance, and the registry record does not report a threshold for an important difference.

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 for 80% power and participants per arm for 90% power. They are not total event counts: this is a continuous-outcome illustration, and the figures represent participants in each of two arms. The accompanying planning relationship shows how the required number changes as the assumed effect changes; it is not a report of the trial's original design calculation.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. The registry record does not report the original sample-size justification or the assumptions used by the trial investigators when planning enrollment.

In plain terms, the 80% power column gives the number of participants per arm for a planning scenario designed to have an 80% chance of detecting the assumed effect under those assumptions. The 90% column uses a higher target chance of detection and consequently requires more participants for the same assumed effect. These are planning concepts, not guarantees about what a particular study will detect.

The rows consider planning for the full observed effect and for smaller fractions of it. Smaller effects need more participants to detect, all else held constant. The numbers are planning illustrations computed from the observed effect, not observed power. They should not be read as a retrospective judgment that the completed trial did or did not have adequate 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 = -0.120; pooled standard deviation σ = 1.018.
2. n = 2 × (1.96 + 0.842)² × 1.018² / -0.120² = 1,129.2, rounded up to 1,130 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 <- -0.12                      # observed difference in means
sigma <- 1.01775525426094                     # 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(972283)
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 = 1,130 (80% power), 1,512 (90% power)
 75% of observed effect: n per arm = 2,008 (80% power), 2,688 (90% power)
 50% of observed effect: n per arm = 4,517 (80% power), 6,047 (90% power)
power.t.test: 1130.1 
Simulated power at n = 1,130 per arm: 0.799 (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

Multiplicity arises when several outcomes or comparisons are tested. This registry record lists a primary endpoint and multiple secondary outcomes, including week-78 HbA1c change, glucose profiles at weeks 52 and 78, and rates of confirmed and nocturnal confirmed hypoglycaemic episodes. The registry record does not report whether the investigators used a hierarchy, adjusted p-values, or otherwise controlled the overall chance of false-positive findings. The posted secondary p-values are unadjusted, so they should be interpreted with that limitation in mind.

The primary outcome description identifies the full analysis set as all randomized participants and states that missing values were imputed using last observation carried forward. The record does not report how many values were missing, when they were missing, or why participants lacked measurements. It also does not provide sensitivity analyses using alternative missing-data methods. As a general matter, carrying forward the last observed value assumes that this value is an appropriate substitute for the missing follow-up value; that assumption may not hold in every setting.

Missing-data methods for the extension and other secondary outcomes are not reported in the registry record. The record also does not report the detailed statistical analysis plan, the original sample-size justification, interim analyses, covariate adjustments, or the method used to produce the posted interval estimates. No reported analyses are listed for the secondary outcomes.

These absences do not invalidate the posted summaries, but they limit how fully a reader can audit the analyses or determine whether the reported tests match prespecified methods. The registry record does not describe an equivalence or non-inferiority framework, and the primary result should not be interpreted as establishing either. Distinguishing what the registry reports from what it leaves unreported is important when weighing the primary and secondary evidence.

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: hypoglycaemia (1.7%), cardiac failure congestive (1.2%), coronary artery disease (1.2%), chronic obstructive pulmonary disease (1.2%), coronary artery stenosis (0.8%).

The registry reports serious adverse events for 139 of 753 participants at risk in the insulin degludec group and 53 of 251 participants at risk in the insulin glargine group. It also reports other adverse events for 447 of 753 and 146 of 251 participants, respectively. These are counts of participants with events and the corresponding numbers at risk, not event rates calculated from person-time.

The listed serious adverse event terms include hypoglycaemia at 1.7%, cardiac failure congestive at 1.2%, coronary artery disease at 1.2%, chronic obstructive pulmonary disease at 1.2%, coronary artery stenosis at 0.8%, and myocardial infarction at 0.8%. The registry record does not make clear in this summary how these listed percentages are distributed by treatment group, so they should not be assigned to either group. Death counts are not reported in the registry record.

These adverse-event summaries are descriptive. They do not, by themselves, establish that a treatment caused an event or that the groups differ in safety. The record does not provide adjusted safety comparisons, exposure-adjusted rates, or further detail about event ascertainment in the posted results.

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

The primary result estimates a mean difference in change in HbA1c after 52 weeks. The observed group means were -1.17 for insulin degludec and -1.29 for insulin glargine, with an unadjusted difference of -0.12 for insulin glargine minus insulin degludec. The reported interval includes zero, and the unadjusted p-value is 0.099. Thus, the estimate points toward a more negative mean change in the insulin glargine group, but the result remains uncertain about the size and direction of the underlying difference.

This does not show that the groups are equivalent, nor does it show that one treatment is clinically preferable. Equivalence and non-inferiority require an appropriate prespecified margin and analysis; those are not reported in the registry record. The record also does not provide a threshold for a clinically important HbA1c difference. Statistical significance and clinical importance are distinct questions.

The secondary continuous outcomes show unadjusted contrasts favoring more negative HbA1c change at week 78 and lower mean glucose-profile values in the insulin glargine group at weeks 52 and 78. These results add context, but they are secondary comparisons and the registry record does not report a multiplicity strategy or complete analyses. The registry lists hypoglycaemic episode outcomes but does not report numeric results for them in the posted secondary data.

Group averages do not describe every participant, and adverse-event counts do not establish causality. The results apply to the trial populations and definitions recorded; they do not determine what is appropriate for an individual. No treatment recommendation follows from these summaries alone.

17. Why This Trial Matters Statistically

This trial illustrates why an estimate, an interval, and a p-value should be read together. The primary point estimate is modest in magnitude, while its interval crosses zero and its unadjusted p-value is 0.099. Treating that p-value as a binary verdict would discard information about the range of differences compatible with the data and could encourage an unsupported claim of equivalence.

It also shows how secondary outcomes can add context without replacing a primary endpoint. The posted secondary continuous results have a consistent direction, but the registry record does not report a multiplicity strategy or the full analysis details. Multiple outcomes make it important to distinguish exploratory or descriptive evidence from confirmatory evidence, especially when only selected outcomes have posted numeric results.

The record makes some analysis choices visible, including the full analysis set and last observation carried forward for the primary endpoint. At the same time, it leaves other important details unreported, such as the original sample-size justification, the confidence interval method and level, and secondary-outcome missing-data handling. These gaps demonstrate why registry results are most useful when read with attention to both stated methods and information that is not reported.

Finally, the planning illustrations emphasize a basic design principle: smaller effects require more participants to detect under otherwise unchanged assumptions. Those calculations are not a substitute for the trial's original design rationale and are not a measure of the completed study's 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 record provides a limited account of the statistical methods. It does not report the detailed analysis model, the interval-estimation method or confidence level, the randomization procedure, or allocation concealment. It also does not report the trial's original sample-size justification, interim analyses, or a complete protocol-level statistical plan. These omissions make it difficult to assess all design and analysis choices from registry results alone.

For the primary endpoint, last observation carried forward is specified, but the amount and pattern of missing data are not reported, nor are sensitivity analyses under other assumptions. Missing-data handling for the extension and secondary outcomes is not reported in the registry record. Extension participation and follow-up details are also not given in the posted information.

The registry reports multiple secondary outcomes, while the posted numeric secondary results do not include every outcome on the list. No multiplicity adjustment or testing hierarchy is reported. This makes the secondary p-values less suitable for confirmatory interpretation. In addition, the listed serious adverse event percentages are not clearly assigned to treatment groups in the summary, and deaths are not reported in the registry record.

The primary comparison is an unadjusted contrast based on the posted summary statistics, and the registry lists no reported analyses. The record does not state a clinically important difference or an equivalence or non-inferiority margin. These limitations constrain conclusions about clinical relevance and about how the results relate to a prespecified inferential framework.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes — NCT00972283.
• Registry record last updated 2017-04-06; status last verified 2017-03.
• 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 describes a completed, randomized, parallel-group, open-label phase 3 trial with enrollment of 1006. It compared insulin degludec with insulin glargine in basal-bolus regimens that included mealtime insulin aspart, with metformin or pioglitazone where applicable. The primary endpoint was change in HbA1c from baseline to week 52 in the full analysis set, with last observation carried forward used for missing primary outcome data.

The primary mean difference was -0.12 for insulin glargine minus insulin degludec, with an interval from -0.263 to 0.023 and an unadjusted p-value of 0.099. Posted secondary continuous results show differences at week 78 and in glucose profiles, but the registry does not report a multiplicity strategy or full secondary analyses. Several design and analysis details, including the original sample-size justification, are not reported in the registry record.