Comparison of the Efficacy and Safety of Two Intensification Strategies in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of the Efficacy and Safety of Two Intensification Strategies in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin (NCT01388361), a randomized phase 3 study. The primary outcome is Change From Baseline in HbA1c (%) (Glycosylated Haemoglobin).

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, parallel-group trial with no masking. The registry reports an enrollment of 413 and a completed status. The recorded start was 2011-09, and primary completion was 2012-07. Novo Nordisk A/S is listed as sponsor.

The trial concerned treatment intensification in subjects with type 2 diabetes inadequately controlled on basal insulin and metformin. According to the brief summary, eligible subjects had HbA1c at or above 7% at the end of the NN1250-3643 trial and were randomized to intensification. Subjects below 7% could continue insulin degludec. All subjects were to continue their pre-trial metformin treatment.

The registry lists insulin degludec alone, insulin degludec plus liraglutide, and insulin degludec plus insulin aspart with the largest meal. It identifies the insulin-degludec arm as non-randomized. The posted primary outcome counts are 236 for insulin degludec, 88 for insulin degludec plus liraglutide, and 89 for insulin degludec plus insulin aspart with the largest meal. These are the outcome-specific counts, not a statement about how many subjects were randomized.

The registry record does not report the trial’s original sample-size assumptions, the detailed randomization procedure, or a statistical analysis plan. The allocation is recorded as randomized, but the details of how the allocation sequence was generated or concealed 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.

Before assignment: Subjects treated with Insulin degludec (IDeg) once daily (OD) + metformin in trial NN1250-3643 (NCT01193309) were eligible for this trial. Eligible subjects with an HbA1c \>/=7.0% at the end of 3643 trial were qualified to enter the extension trial 3948 and be randomised to add either liraglutide/insulin aspart to their prior IDeg + Met treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The FAS and NAS included all randomised and non-randomised subjects respectively, 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.

Population: The full analysis set (FAS) included all randomised patients except for 7 subjects (2 subjects with IDeg+ liraglutide; 5 subjects with IDeg+IAsp arm) fasting plasma glucose (FPG) values were missing at baseline. Non-randomised set (NAS) included all non-randomised subjects, the FPG values were missing for 10 subjects at baseline.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in HbA1c (%) (Glycosylated Haemoglobin), measured over week 0, week 26.

The primary endpoint was change from baseline in HbA1c, expressed as a percentage of glycosylated haemoglobin, from week 0 to week 26. HbA1c is a measure of glycosylated haemoglobin in blood; in general, it is used in diabetes studies as an indicator of glucose exposure over a period of time rather than as a single-time-point glucose measurement.

The endpoint is a change score: the posted group means describe the mean difference between the baseline measurement and the measurement at week 26. A negative mean change indicates that the measured HbA1c was lower at follow-up than at baseline on average; a positive mean change indicates a higher value on average. This describes group averages and does not establish that every subject had a change in the same direction.

The registry describes the population as the FAS for randomized subjects and the NAS for non-randomized subjects. Missing data were imputed using last observation carried forward. The endpoint’s posted descriptive values include the number assessed, the mean change, and the standard deviation for each arm. The registry record does not report additional details about how the endpoint was modeled in the sponsor’s analysis.

7. Results Posted in the Registry

• IDeg + Liraglutide: mean -0.74 versus 0.10 on control; difference -0.84 (95% CI -1.00 to -0.68), standardized effect d = -1.64; z-test p = <0.001.
• IDeg + IAsp OD: mean -0.39 versus 0.10 on control; difference -0.49 (95% CI -0.65 to -0.33), standardized effect d = -0.97; 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.

Change From Baseline in Fasting Plasma Glucose (FPG)

• 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:
  • IDeg + Liraglutide: mean -0.14 versus -1.23 on control; difference 1.09 (95% CI 0.50 to 1.68), standardized effect d = 0.50; z-test p = <0.001.
  • IDeg + IAsp OD: mean -0.04 versus -1.23 on control; difference 1.19 (95% CI 0.53 to 1.85), standardized effect d = 0.52; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for IDeg + Liraglutide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for IDeg + IAsp OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Body Weight

• 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:
  • IDeg + Liraglutide: mean -1.00 versus 0.10 on control; difference -1.10 (95% CI -1.54 to -0.66), standardized effect d = -0.46; z-test p = <0.001.
  • IDeg + IAsp OD: mean 0.30 versus 0.10 on control; difference 0.20 (95% CI -0.19 to 0.59), standardized effect d = 0.09; z-test p = 0.320.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for IDeg + Liraglutide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IDeg + IAsp OD and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary HbA1c result to fasting plasma glucose and body weight. They do not all move in the same comparative pattern. The fasting plasma glucose contrasts place the intensification-arm mean changes above the insulin-degludec-arm mean change, whereas the HbA1c contrasts are below it. For body weight, the liraglutide contrast is below the reference mean change; the insulin-aspart contrast is small and its confidence interval includes zero.

These endpoints describe different aspects of the observed outcomes and should be considered alongside, rather than as confirmation of, the primary result. A pattern across measures can be informative, but a contrast on one measure does not determine the result on another. The registry record does not report a combined outcome or a model linking the secondary outcomes to HbA1c.

The secondary outcome comparisons are unadjusted recalculations from posted summaries, and no sponsor-reported analyses are listed. Multiple outcomes and multiple comparisons create more opportunities for apparently notable findings. Unless an analysis plan specifies how those comparisons are controlled or prioritized, their p-values should carry less weight than a result from a prespecified primary analysis with a reported statistical plan. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for the secondary outcomes.

Accordingly, the secondary summaries add context about the observed directions and variability, but they do not independently settle the primary question or establish a broader pattern of benefit. Their interpretation is also limited by the same population, follow-up period and missing-data approach described for the primary outcome.

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

• Change From Baseline in Fasting Plasma Glucose (FPG)
• Change From Baseline in Body Weight
• Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, and the registry reports it as a mean change with a standard deviation. A mean is the arithmetic average of the observed change scores in an arm. It provides a compact description of the group’s central tendency, but does not show the full distribution of individual outcomes. The standard deviation describes spread among individual observations; a larger standard deviation indicates more variability around the mean.

The recalculated comparisons use the insulin-degludec arm as the reference. A mean difference is the difference between the two arm means, with the direction depending on which arm is subtracted from which. In the posted primary contrasts, the intensification-arm means are compared with the insulin-degludec mean. A negative estimate therefore means the intensification arm’s average change was lower. This sign does not by itself say whether a difference is clinically important.

The recalculated mean differences, confidence intervals and unadjusted p-values are based on the posted arm-level summary statistics. They are simple unadjusted recalculations, not the trial sponsor’s own reported inferential analysis. The registry record lists no reported analyses for the primary or secondary outcomes. Consequently, the registry does not establish whether the sponsor used a different model, adjusted for baseline factors, or applied a particular approach to inference.

A confidence interval expresses uncertainty around an estimated contrast. In general, it gives a range of values reasonably compatible with the data and the calculation’s assumptions. A narrower interval indicates greater precision than a wider interval, but the interval does not represent the range of individual responses. Whether an interval crosses zero is a way to assess whether the data are compatible with no mean difference under the calculation used; it does not measure the clinical importance of the difference.

A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the test. The posted p-values are unadjusted. They do not account for the number of outcomes or contrasts being considered. An unadjusted p-value is therefore not a complete summary of evidence when many comparisons are examined. The registry record does not report a multiplicity strategy or identify a prespecified hierarchy among outcomes.

For continuous outcomes, a standard error describes uncertainty in an estimated mean, unlike a standard deviation, which describes spread among observations. The recalculations use arm-level standard deviations and sample sizes to estimate the uncertainty of contrasts. This type of summary-based calculation cannot recover information that is not present in the arm-level summaries, such as individual-level covariate relationships or an adjusted model’s results. No adjusted estimates should be inferred from these calculations.

The registry states that missing values were imputed using last observation carried forward. In general, this approach carries a subject’s last recorded value forward to a later assessment when that later value is missing. It is a method for handling missing outcome measurements, but it does not make the missing values observed measurements. The record does not report how many measurements were missing, the reasons for missingness, or sensitivity analyses using alternative assumptions.

The endpoint description distinguishes the FAS for randomized subjects from the NAS for non-randomized subjects. The insulin-degludec arm is explicitly labeled non-randomized, so its comparison with randomized intensification arms should not be read as if all arms necessarily arose from the same randomized contrast. The record does not provide enough detail to characterize how the populations were combined or analyzed beyond the FAS and NAS description.

Effect-size and sample-size illustrations use standardized quantities as well as the original measurement scale. In general, a standardized mean difference expresses a mean contrast relative to a measure of variability, allowing outcomes on different scales to be considered in a common unit. Such a quantity does not change the original endpoint’s units or replace the mean difference in HbA1c percentage points. The posted planning illustrations use the observed effect as a starting point and show how required sample sizes change when the assumed effect is reduced.

The registry record does not report the original sample-size justification, original power target, interim analyses, or detailed analysis plan. The separate planning illustrations use their stated assumptions and are not evidence about the trial’s original design. General principles such as confidence-interval interpretation and the distinction between a standard deviation and a standard error apply regardless of whether those details are available.

11. Confidence Intervals and Precision

The recalculated primary mean difference for insulin degludec plus liraglutide versus insulin degludec is -0.84, with a confidence interval from -1.001 to -0.679. The upper bound is displayed in the registry-derived calculation with more than three decimal places; it is not repeated to keep displayed values to no more than three decimal places. The interval lies below zero. For insulin degludec plus insulin aspart versus insulin degludec, the mean difference is -0.49, with a confidence interval from -0.648 to -0.332. This interval also lies below zero.

These intervals describe uncertainty in the recalculated mean differences, not variability among individual subjects. The arm-level standard deviations indicate that individual change scores varied within each group, while the confidence intervals address uncertainty in the between-arm estimates. Both comparisons have unadjusted p < 0.001, but neither the p-value nor the interval addresses multiplicity.

Precision depends on the data and the calculation assumptions. The posted recalculations use summary statistics, and the registry does not report a sponsor analysis to compare against them. The confidence intervals should therefore be read as uncertainty estimates for these unadjusted recalculations rather than as a substitute for an unreported adjusted analysis. They describe the magnitude of the estimated contrasts more informatively than a significance label alone, but do not determine clinical importance.

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 illustrations express requirements as participants per arm for the continuous comparisons in this trial. They are not totals across arms and do not report total events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each scenario, the assumed effect is the stated fraction of the observed effect.

The 80% power column gives the illustrative participants per arm for a design intended to have an 80% chance of detecting the assumed effect under those planning assumptions, if the effect and model assumptions hold. The 90% power column uses a higher target chance of detection and therefore generally requires more participants per arm for the same assumed effect. These are design calculations, not estimates of the trial’s achieved ability to detect an effect.

Each row changes the assumed effect relative to the observed effect. Planning for 75% of the observed effect or 50% of the observed effect assumes a smaller contrast than planning for 100%. Smaller effects are harder to distinguish from random variation, so they require more participants for the same target power. The magnitude of the increase depends on the variability and effect size in the particular comparison.

The registry record does not report the trial’s original design assumptions, so the illustrations should not be taken as an explanation of why the study enrolled its recorded number. This is not observed power; it is a planning illustration based on the observed effect and the stated assumptions. The registry also notes that the event-count convention for time-to-event outcomes differs, but these posted comparisons are continuous outcomes and use participants per arm.

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 = -0.840; pooled standard deviation σ = 0.511.
2. n = 2 × (1.96 + 0.842)² × 0.511² / -0.840² = 5.8, rounded up to 6 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 <- -0.84                      # observed difference in means
sigma <- 0.510639289980755                     # 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(1388361)
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 = 6 (80% power), 8 (90% power)
 75% of observed effect: n per arm = 11 (80% power), 14 (90% power)
 50% of observed effect: n per arm = 24 (80% power), 32 (90% power)
power.t.test: 6.9 
Simulated power at n = 6 per arm: 0.724 (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 lists one primary outcome and several secondary outcomes, with comparisons against the insulin-degludec arm. The recalculated p-values are unadjusted. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which secondary comparisons, if any, were intended to be confirmatory. When multiple outcomes and contrasts are examined, unadjusted p-values do not account for the increased chance of a nominally unusual result across the full set of tests. The posted p-values should therefore be treated as contrast-specific rather than as an overall error-controlled conclusion.

The primary outcome population description distinguishes the FAS, comprising randomized subjects, and the NAS, comprising non-randomized subjects. Missing data were imputed using last observation carried forward. This makes the handling of missing measurements part of the reported endpoint definition, but does not reveal how much data were missing or whether missingness differed by arm. The registry record does not report missing-data counts, reasons for missingness, or sensitivity analyses.

The non-randomized insulin-degludec arm is an important design distinction. Randomization is recorded for the trial, but the insulin-degludec arm is labeled non-randomized. The registry record does not report enough detail to establish that comparisons with this arm have the same protection against confounding as a comparison between randomized arms. The posted recalculations are unadjusted and cannot account for possible differences in participant characteristics.

The registry record also does not report the original statistical analysis plan, interim analyses, or the sponsor’s outcome analyses. These omissions limit assessment of prespecification, adjustment, and the intended interpretation of the reported outcomes. They do not by themselves establish that a particular analysis was or was not conducted; they mean that it is not reported in the registry record.

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: vitreous detachment (1.2%), pancreatitis (1.2%), humerus fracture (1.2%), diabetes mellitus inadequate control (1.2%), cerebrovascular accident (1.2%).

The registry lists serious adverse events affecting 11 of 236 subjects in the insulin-degludec arm, 4 of 87 in the insulin-degludec-plus-liraglutide arm, and 5 of 86 in the insulin-degludec-plus-insulin-aspart arm. It lists other adverse events affecting 64 of 236, 40 of 87, and 18 of 86, respectively. These are counts with the corresponding at-risk counts shown in the registry; they should not be treated as comparative rates calculated.

Serious-event terms listed with percentages include vitreous detachment, pancreatitis, humerus fracture, diabetes mellitus inadequate control, and cerebrovascular accident at 1.2% each, and coronary artery disease at 1.1%. The registry does not provide term-specific counts in this summary. Deaths are not reported in the registry record.

These figures describe events recorded in the trial and do not establish that a treatment caused an event. The registry’s arm labels and differing at-risk counts should be kept in view when reading the counts. The record does not provide further detail about event timing, severity grading beyond the serious-event category, or comparative safety analyses.

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

The posted primary results show lower mean HbA1c change in each intensification arm than in the insulin-degludec arm over the 26-week treatment period. The unadjusted recalculated mean differences are -0.84 for insulin degludec plus liraglutide and -0.49 for insulin degludec plus insulin aspart, with unadjusted p < 0.001 for each comparison. This describes the posted group summaries and their recalculated contrasts.

It does not provide a direct statistical comparison between liraglutide and insulin aspart. A difference in the size of their separate contrasts with insulin degludec is not itself a tested head-to-head contrast. The registry’s stated comparison of intensification strategies is broader than the particular recalculations available from the posted summary statistics.

These results also do not establish how the treatments would compare in people outside the study’s eligibility conditions, at other follow-up times, or under other treatment settings. The population was selected based on HbA1c at the end of a preceding trial, and the record describes the insulin-degludec arm as non-randomized. That design feature is relevant to interpretation of comparisons with that arm.

Statistical evidence is not the same as clinical importance. The confidence intervals and p-values characterize uncertainty under the unadjusted calculations, but the registry record does not specify a threshold for a clinically important HbA1c difference. These results do not establish individual outcomes, long-term outcomes, or a complete balance of benefits and harms. They are summaries of the outcomes and safety events recorded for this trial.

17. Why This Trial Matters Statistically

This trial is statistically notable for placing two intensification strategies alongside a basal-insulin reference in a population selected for HbA1c at or above 7% at the end of a preceding trial. That eligibility pathway shapes the population to which the posted results relate. The registry also identifies the insulin-degludec-only arm as non-randomized, making it important to distinguish the trial’s randomized allocation from the structure of each arm-level comparison.

The primary endpoint is a continuous change measure, which permits interpretation of average differences and their uncertainty rather than only a binary outcome. The posted recalculations pair mean differences with confidence intervals, making the estimated direction and precision visible. The registry’s secondary endpoints also show why a trial cannot be reduced to one summary: different outcomes can have different comparative patterns.

At the same time, this record illustrates the limits of registry-level summaries. There are no sponsor-reported analyses listed, and details of the analysis plan, multiplicity handling, missingness, and original sample-size justification are not reported in the registry record. Recalculations from summary statistics can support descriptive interpretation, but cannot recover all the information needed to evaluate an adjusted analysis or the trial’s prespecified inferential strategy.

The statistical value of the record is therefore both in the outcomes it reports and in the design distinctions readers must retain. Interpretation requires attention to the selected population, non-randomized reference arm, 26-week endpoint, and unadjusted nature of the recalculations.

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 outcome summaries cover change through week 26. The registry record does not report longer follow-up results for the posted outcomes, so these summaries do not describe durability beyond that timeframe.

The eligibility pathway is specific: subjects eligible for randomization had HbA1c at or above 7% at the end of the NN1250-3643 trial, while those below 7% could continue insulin degludec. This limits how directly the results can be applied to populations selected in other ways. The record also describes the insulin-degludec arm as non-randomized, which makes comparisons with that arm different in design from a comparison between two randomized arms.

The registry reports last observation carried forward for missing outcome data but does not report missing-data counts, reasons, or sensitivity analyses. It also does not list sponsor-reported analyses, a statistical analysis plan, or a multiplicity approach. The recalculated comparisons are unadjusted and based on posted arm summaries, so they do not provide adjusted estimates or account for participant-level covariates.

For safety, the registry provides affected counts and selected serious-event terms, but deaths are not reported in the registry record. The available summary does not provide event timing or enough detail to independently assess differences in exposure or event risk. These limitations concern what can be established from the registry record; they do not establish that unreported analyses or details were absent from the trial conduct.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparison of the Efficacy and Safety of Two Intensification Strategies in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin — NCT01388361.
• Registry record last updated 2017-03-06; status last verified 2017-01.
• Results first posted 2015-11-26.
• 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

NCT01388361 was a completed phase 3, randomized, parallel-group trial with no masking, sponsored by Novo Nordisk A/S. It compared adding liraglutide or insulin aspart with the largest meal to insulin degludec and continued metformin in subjects with type 2 diabetes. The registry reports enrollment of 413 and primary completion in 2012-07.

The primary endpoint was change in HbA1c from baseline to week 26. The posted means were 0.1 for insulin degludec, -0.74 for insulin degludec plus liraglutide, and -0.39 for insulin degludec plus insulin aspart. Unadjusted recalculated comparisons against insulin degludec were -0.84 and -0.49, respectively, with p < 0.001 for each.

The registry identifies the insulin-degludec arm as non-randomized, reports last observation carried forward for missing data, and lists no sponsor analyses. Interpretation is consequently based on the posted summaries and unadjusted recalculations, with the design and reporting limitations.