Duration of The Honeymoon Phase of Type 1 Diabetes: A Comparison of Insulins Detemir, Glargine and NPH: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Duration of The Honeymoon Phase of Type 1 Diabetes: A Comparison of Insulins Detemir, Glargine and NPH (NCT00564018), a randomized na study. The primary outcome is C-peptide Area Under the Curve.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. The three treatment groups were detemir, NPH insulin and glargine. Each arm description says participants received the assigned insulin together with aspart at diagnosis. The registry lists the study as terminated. The reason for termination is not reported in the registry record.

The registry lists enrollment as 33, while each arm description states that 24 subjects were randomized to that arm. The record does not explain this mismatch. The primary outcome includes 10 participants in the detemir group, 7 in the NPH group and 10 in the glargine group who completed the 6-month mixed meal tolerance test. The registry does not explain the differences between the enrollment, arm-description and outcome counts.

The primary outcome description says C-peptide was measured at 1, 6 and 12 months after diagnosis. The primary comparison, however, was at 6 months. A secondary outcome was glycemic control, recorded as HgbA1c at 6 months. The registry lists two outcome measures, but it does not report inferential analyses for the primary outcome. The study phase is listed as NA. Further details on the randomization procedure, allocation concealment, sample-size justification and the reason for termination are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who completed 6 month mixed meal tolerance test (MMTT)s

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: Subjects who completed randomization into one of the three treatment arms

6. Primary Endpoint

The registry lists the primary outcome as C-peptide Area Under the Curve, measured over Although measured at 1, 6 and 12 months, the primary outcomes was a comparison between treatment groups at 6 months after diagnosis.

The primary endpoint is C-peptide area under the curve (AUC), measured in ng*hr/mL. C-peptide is released alongside insulin made by the pancreas, so its concentration after a meal challenge can be used to assess the body’s endogenous insulin secretion. In this trial, participants completed a mixed meal tolerance test using Boost, and C-peptide measurements were combined into an AUC using the trapezoidal method.

In general, an AUC summarizes measurements across a period of time, rather than relying on a single measurement. The trapezoidal method approximates the area between observed measurement points by connecting them with straight lines. This can provide a summary of the response during the test. It does not, by itself, describe all aspects of glucose regulation or establish how long a participant remains in a so-called honeymoon phase.

The registry says measurements were taken at 1, 6 and 12 months, but the primary comparison was between groups at 6 months. Results are reported as medians with interquartile ranges. The analysis population is defined as subjects completing the 6-month test. The registry record does not report a primary-outcome confidence interval, a statistical test or an adjusted comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the posted summaries can and cannot show. The explanations of these concepts are general; the specific trial methods are described only to the extent recorded in the registry.

Why report a median and interquartile range?

The median is the middle value when observations are ordered. The interquartile range (IQR) describes the span between the lower and upper quartiles, which contain the middle half of observations. In general, a median and IQR can be useful when measurements are skewed or when a few values could strongly affect a mean. Here, the registry identifies the primary outcome summary as a median with IQR. It does not explain why this summary was selected or report the individual participant values, so the shape of each group’s distribution cannot be assessed from the summaries alone.

The IQR is not a confidence interval. An IQR describes variation among observed participants; a confidence interval describes uncertainty in an estimate of a population quantity. The primary outcome record gives IQRs but no confidence intervals for group medians or between-group contrasts. The ranges should therefore not be interpreted as intervals quantifying the precision of a treatment effect.

What does an AUC represent?

In general, area under the curve combines measurements across a period into a single summary. In this study, C-peptide was measured during a mixed meal tolerance test, and the trapezoidal method was used to calculate the AUC. The trapezoidal approach approximates the area between measurement times by treating the trajectory between observed points as straight. The registry does not give the test’s measurement schedule, the number of C-peptide samples or further calculation details.

An AUC can capture the overall response during the test, but it compresses a set of measurements into one value. It does not show whether a group differed at every measurement time or how the response changed over time. Although the registry says measurements occurred at 1, 6 and 12 months, it specifies the primary comparison at 6 months. No repeated-measures analysis or longitudinal comparison is reported.

How should uncertainty in the secondary comparison be read?

The posted secondary comparison is an unadjusted recalculation of the mean HgbA1c difference between glargine and detemir. A confidence interval gives a range of effect estimates compatible with the data under the calculation’s assumptions; a wide interval signals limited precision. In general, when an interval includes zero for a difference, the data do not clearly distinguish a positive difference from no difference or a negative difference at the interval’s confidence level. The reported interval includes zero, and the unadjusted p-value is 0.584. These are not adjusted trial analyses.

General caution is needed when reading p-values: a p-value is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of an effect. It summarizes how unusual data at least as incompatible with a specified null would be under the assumptions of a statistical test. The registry record does not report the trial’s planned test, whether the comparison was prespecified, or how multiple outcomes and group comparisons were handled.

What does the planning illustration mean?

The planning figures are illustrations based on the observed effect in the unadjusted secondary comparison, not the trial’s original design and not observed power. The assumptions stated in the registry are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. For planning for 100% of the observed effect, the figures are 272 participants per arm for 80% power and 364 participants per arm for 90% power. For planning for 75% of the observed effect, they are 484 participants per arm for 80% power and 647 participants per arm for 90% power. For planning for 50% of the observed effect, they are 1,088 participants per arm for 80% power and 1,456 participants per arm for 90% power.

In general, smaller effects require larger studies to achieve a chosen power under otherwise similar assumptions. These illustrations depend on the observed effect, which may be imprecise, and on the stated calculation assumptions. They do not demonstrate the power of the completed trial, establish a clinically important effect, or substitute for a prospective sample-size calculation. The original sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies C-peptide AUC at 6 months as the primary outcome and HgbA1c at 6 months as a secondary outcome. It also describes C-peptide measurements at 1 and 12 months, but the primary comparison is at 6 months. The record does not state how many hypotheses were planned, whether other time points were analyzed, or whether the primary and secondary outcomes were arranged in a testing hierarchy.

When several outcomes, time points or pairwise comparisons are tested, the chance of at least one nominally unusual result can increase. General approaches include adjusting significance thresholds, using a prespecified hierarchy, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment or a statistical analysis plan, and no sponsor-reported analyses are listed. The unadjusted secondary comparison should consequently be interpreted with caution.

Missing-data handling and analysis populations are also not described in detail. The primary outcome population is stated as all subjects who completed the 6-month mixed meal tolerance test. That definition indicates a completer-based outcome summary, but the record does not explain why some randomized participants are not represented, how missing measurements were handled, or whether any imputation was performed. It does not report an intention-to-treat analysis or a per-protocol analysis.

The enrollment entry, arm descriptions and outcome counts do not align, and the registry record does not explain why. This limits the ability to trace participants from randomization through outcome assessment. Details on baseline comparability and any adjustment for baseline characteristics are not reported in the registry record. These omissions make it difficult to assess the impact of missing outcomes or to determine whether the posted group summaries reflect the randomized groups as a whole.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry reports zero serious adverse events affecting participants in each of the three safety groups, and zero other adverse events affecting participants in each group. It also reports zero deaths in each group. The numbers listed as at risk differ by outcome group: 11 for detemir, 10 for NPH insulin and 12 for glargine.

These are descriptive counts in the registry record. A zero count means that no events of the listed type were recorded among the participants counted at risk; it does not establish that an event could not occur or that the groups have identical safety profiles. With small numbers of participants, rare events may not be observed, and differences can be difficult to estimate precisely.

The record does not provide further detail on event definitions, follow-up duration for safety, severity beyond the serious-event category, or methods for comparing safety between groups. The safety counts should be read as a summary of reported events, not as a formal equivalence assessment.

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

The posted results describe C-peptide AUC at 6 months among participants who completed a mixed meal tolerance test, along with HgbA1c and adverse-event counts. The primary outcome summaries show different group medians, but the registry record does not report an inferential comparison or uncertainty interval for those differences. The observed medians alone cannot establish that treatment groups differed reliably.

The secondary HgbA1c comparison is an unadjusted recalculation from posted summary statistics. Its estimate is 0.3 percentage points, its interval includes zero, and its unadjusted p-value is 0.584. This indicates substantial uncertainty and does not establish a clear difference in that comparison. It is not a reported sponsor analysis and does not resolve the primary-outcome question.

These results do not establish whether any treatment changes the duration of the honeymoon phase. The primary measure is C-peptide AUC at a specified time point, rather than a reported time-to-event measure of honeymoon-phase duration. The registry also does not report a longitudinal treatment comparison across its listed measurement times. No conclusion about benefit, lack of benefit, or equivalence follows from the descriptive summaries alone.

More broadly, interpretation is limited by small outcome groups, the mismatch between enrollment and arm descriptions, incomplete information about missing outcomes, and the absence of a reported statistical analysis plan. The trial is listed as terminated, but the reason is not reported in the registry record. The findings therefore characterize the posted observations and their limitations, rather than providing a definitive answer to the treatment question.

13. Why This Trial Matters Statistically

This trial illustrates why study design, analysis population and uncertainty matter alongside group summaries. The primary outcome is reported as a median and IQR, which describe the observed distribution but do not quantify uncertainty in a between-group effect. Without a reported primary comparison or confidence interval, the ranking of group medians should not be mistaken for a statistically established contrast.

It also illustrates how different outcomes address different questions. C-peptide AUC measures pancreatic insulin secretory capacity during a meal challenge, whereas HgbA1c summarizes glycemic control. Seeing both can provide complementary descriptions, but one result cannot stand in for the other. A reported secondary comparison is unadjusted and has substantial uncertainty, so it should not be promoted to a confirmatory conclusion.

The enrollment and arm-description mismatch, together with the completer-defined primary population, highlights the importance of transparent participant accounting. Without explanations for missing outcomes or the analysis population, readers cannot determine how fully the reported results reflect randomization. Finally, planning illustrations based on an observed effect are not evidence that a completed trial had adequate power; prospective justification and transparent analysis plans are needed to interpret precision and multiplicity.

14. 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.

Several limitations specific to this record affect interpretation. The registry lists enrollment as 33, while the three arm descriptions each state that 24 subjects were randomized. The record does not reconcile those entries. The primary outcome counts are smaller still, and the primary population is defined as participants completing the 6-month test. Reasons for non-completion and the handling of missing outcomes are not reported.

The trial is listed as terminated, but no reason is given. The registry does not report a sample-size justification, the statistical analysis plan, interim analyses, the randomization method, allocation concealment, or baseline characteristics. It is therefore not possible to assess planned precision, the handling of possible baseline imbalance, or whether the posted analyses follow a prespecified plan.

For the primary endpoint, group medians and IQRs are posted without an inferential comparison or confidence interval. For the secondary endpoint, the reported comparison is a recalculation from summary statistics rather than a sponsor-reported analysis, and other pairwise comparisons are not reported. Multiplicity handling is not described. The limited outcome counts and absence of participant-level information further restrict assessment of distributions, missingness and model assumptions.

The registry describes measurements at 1, 6 and 12 months but identifies the primary comparison at 6 months. It does not report a longitudinal analysis or a direct duration-of-honeymoon endpoint. These limitations mean the posted data should be interpreted as incomplete descriptive evidence, not as a comprehensive account of treatment effects over time.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Duration of The Honeymoon Phase of Type 1 Diabetes: A Comparison of Insulins Detemir, Glargine and NPH — NCT00564018.
• Registry record last updated 2019-10-11; status last verified 2019-10.
• Results first posted 2019-10-11.
• 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.

18. Record Summary

The registry describes a randomized, open-label, parallel-group trial comparing detemir, glargine and NPH, each used with aspart at diagnosis of type 1 diabetes. The listed status is terminated. The primary outcome is median C-peptide AUC at 6 months among subjects completing a mixed meal tolerance test. HgbA1c at 6 months is listed as a secondary outcome.

Primary outcome summaries are posted for all three groups, but no inferential primary comparison is reported. An unadjusted secondary comparison of glargine with detemir is recalculated from the posted summaries and remains uncertain. The registry also reports zero serious adverse events, other adverse events and deaths in the listed safety groups. The reason for termination, explanation of participant-count inconsistencies and detailed analysis methods are not reported in the registry record.