A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects (NCT03378635), a randomized phase 3 study. The primary outcome is Time to Plasma Glucose Recovery.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-blind, parallel trial of dasiglucagon, placebo, and GlucaGen® in subjects with type 1 diabetes mellitus and insulin-induced hypoglycemia. The registry lists quadruple masking. It does not identify which participant, investigator, care, or assessment roles were masked, so those operational details are not reported in the registry record.

The registry reports enrollment of 170. The recorded groups were dasiglucagon 0.6 mg, with 82 participants; placebo, with 43; and GlucaGen® 1.0 mg, with 43. Each group received a single fixed subcutaneous dose. The principal objective was to demonstrate superiority of dasiglucagon versus placebo for the glycemic response. Comparing dasiglucagon with GlucaGen® was an additional objective, and GlucaGen® was designated as a reference treatment.

The trial started on 2017-12-07, reached primary completion on 2018-04-27, and is listed as completed. The registry identifies 12 outcome measures and 7 analyses. The primary outcome was time to plasma glucose recovery during the 0-45 minutes after dosing. Secondary outcomes included plasma glucose recovery and changes from baseline, time to target, pharmacodynamic response, and pharmacokinetic measures. The registry lists a full analysis set consisting of randomized patients who received at least one dose. Further details about the randomization procedure, allocation concealment, sample-size justification, and operational conduct 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: Full analysis set of all randomized patients who received at least one dose of trial product

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 Time to Plasma Glucose Recovery, measured over 0-45 minutes after dosing.

The primary endpoint was time to plasma glucose recovery, measured in minutes during the 0-45 minutes after dosing. Recovery meant the first rise in plasma glucose of at least 20 mg/dL (1.1 mmol/L) from baseline, provided rescue intravenous glucose had not been administered. This definition makes the endpoint a time-to-event measure: each participant either reaches the specified glucose increase during the observation period or does not have a recorded recovery event within it.

Time to an event retains information about when recovery occurs, rather than reducing the outcome to whether a threshold was reached at a single measurement. It is useful when the timing of a clinically defined response is the question and when some participants may not experience the event during the observation window. Kaplan-Meier methods can estimate the event-time distribution while accounting for censoring, when the assumptions and event information permit.

The registered endpoint used a Kaplan-Meier estimate and a 95% confidence interval for the median time. For treatment groups without censoring, a distribution-free method was used to calculate the confidence interval for the median. The registry does not give participant-level event times or censoring details, so the posted group estimates cannot show the full shape of the time-to-recovery distributions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a time-to-event outcome. The event is the first qualifying increase in plasma glucose from baseline without rescue intravenous glucose. Each participant contributes information about the time until that event, or about the period during which an event was not observed. In general, time-to-event methods are useful because they can retain information from participants who do not experience the event during the observation window, rather than treating all such observations as if their event time were known.

The registry states that the primary outcome used a Kaplan-Meier estimate. In general, the Kaplan-Meier method estimates the probability of remaining event-free over time, updating the estimate as events occur and accounting for right-censored observations. Censoring means that the event time is not observed in full, although the participant contributes information up to the point of censoring. The validity of the estimate depends on how censoring arises and on other assumptions. The registry does not report detailed censoring counts, reasons, or timing, so these aspects cannot be examined from the posted summary.

The primary result is expressed as a median time with a 95% confidence interval. The median is the time by which half of the estimated event-time distribution has experienced the event, according to the analysis method. A confidence interval describes uncertainty in the estimated median under the method; it is not a range containing a fixed proportion of individual participants. For groups without censoring, the registry says a distribution-free method was used to compute the median's confidence interval. The exact implementation details are not reported in the registry record.

The treatment comparison used a log-rank test. In general, the log-rank test compares event-time distributions across groups using information over the follow-up period, rather than comparing only the two medians. Its p-value quantifies how incompatible the observed data are with the test's null hypothesis, under the test assumptions. A small p-value does not measure the magnitude or clinical importance of an effect. The registry reports p < 0.001 for dasiglucagon versus placebo, but no log-rank effect estimate or confidence interval for the comparison is listed.

The primary analysis population is described as the full analysis set of all randomized patients who received at least one dose of trial product. This definition includes randomized, treated patients; it is not identical to a definition that includes every randomized participant regardless of treatment receipt. The registry does not give counts excluded from this analysis set or describe how any such exclusions were handled.

Secondary continuous outcomes use different summaries and methods. For the pharmacodynamic area-under-the-effect-curve outcome, group results are presented as means and standard deviations. A mean summarizes the average observed value, while a standard deviation describes spread among observations. The registry also reports an ANCOVA analysis for dasiglucagon versus placebo, with a mean difference (net), 95% confidence interval, and p-value. In general, ANCOVA compares groups while adjusting for covariates specified in the analysis model. The covariates and model details are not reported in the registry record, so the meaning of the adjusted estimate cannot be fully reconstructed from the summary alone.

Unadjusted recalculations from group summary statistics are distinct from the registered analysis. They can provide a simple comparison based on posted means, standard deviations, and group sizes, but they do not reproduce a covariate-adjusted ANCOVA model or account for information not contained in those summaries. The recalculated confidence intervals and p-values are therefore not a replacement for the sponsor's registered analysis. Their role is descriptive and depends on the assumptions used for the recalculation.

General sample-size calculations are planning illustrations rather than evidence about the trial's achieved power. A planning calculation depends on choices such as the target effect, significance level, allocation, and statistical model. The registry does not report the trial's sample-size justification or the assumptions used to choose enrollment. It also does not report an interim analysis plan. Such details should not be inferred from the observed results or from a planning illustration based on an observed effect.

Finally, a confidence interval and a p-value answer different questions. A confidence interval indicates a range of effect values compatible with the data and method at its stated confidence level; a p-value assesses compatibility with a specified null hypothesis. Neither alone addresses bias, generalizability, or the clinical meaning of an endpoint. Those judgments require the design, analysis details, endpoint definition, and population to be considered together.

10. Analyses Reported by the Sponsor

For the primary dasiglucagon-versus-placebo comparison, the registry reports the sponsor's log-rank analysis as p < 0.001. The posted medians and their confidence intervals are descriptive estimates of time to recovery; the record does not include a recalculated between-group effect estimate for the primary endpoint. The log-rank result therefore remains the registered inferential result, and the median values should not be read as a replacement for it.

For the secondary pharmacodynamic area-under-the-effect-curve outcome, the registry reports an ANCOVA mean difference (net) of 0.131, with a 95% confidence interval of 0.1 to 0.171 and p < 0.001 for dasiglucagon versus placebo. Separate unadjusted recalculations from posted group summaries give a mean difference of 17.43, with a 95% confidence interval of 16.01 to 18.85 and p < 0.001. These quantities do not align numerically, and the ANCOVA estimate is labeled “net,” whereas the recalculation is an unadjusted comparison of group summaries. Covariates, outcome transformations, and model details needed to reconcile the scales are not reported in the registry record. The registry does not flag a discrepancy. The sponsor's own analysis takes precedence; the recalculation should be viewed as a summary-statistic check, not as a correction or alternative primary analysis.

11. Multiplicity, Missing Data and Analysis Populations

The registry reports a primary endpoint and multiple secondary outcomes, but a multiplicity plan is not reported in the registry record. It is therefore not possible to determine from the record whether secondary hypotheses were tested in a hierarchy, whether p-values were adjusted, or whether any family of outcomes was designated for confirmatory inference. This matters because testing multiple hypotheses can increase the chance of at least one small p-value even when no adjustment is made. The registered primary log-rank comparison is more directly interpretable as the main inferential result than a collection of unadjusted secondary tests.

The record does not report interim analyses, stopping boundaries, or a plan for repeated looks at accumulating results. It also does not report the sample-size justification, target effect, or design assumptions used to set enrollment. Those omissions prevent an assessment of whether the planned enrollment was based on a particular power target or whether the analysis plan changed during the trial.

The primary population is described as all randomized patients who received at least one dose. The registry does not provide the number of randomized participants who did not receive a dose, exclusions from the full analysis set, or detailed accounting of participants contributing to each endpoint. Missing-data counts, reasons for missingness, imputation methods, and sensitivity analyses are not reported in the registry record. For a time-to-event endpoint, censoring information is also important; detailed censoring counts and reasons are not reported.

These gaps do not erase the reported estimates, but they limit independent evaluation of how missing observations, exclusions, and the multiplicity of outcomes may affect interpretation. A complete statistical assessment would require the prespecified analysis plan and participant-level accounting, neither of which is described in the registry summary.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists zero serious adverse events in each of the three groups: dasiglucagon 0.6 mg, placebo, and GlucaGen® 1.0 mg. It also lists zero deaths in each group. These are the posted counts for the summarized trial population; they do not establish that no serious event could occur outside the trial or under different conditions.

The registry separately reports participants affected by other adverse events: 66 of 82 in the dasiglucagon group, 14 of 43 in the placebo group, and 32 of 43 in the GlucaGen® group. These are counts of participants with other adverse events, not counts of all event episodes. The posted summary does not include the terms of the non-serious events, their severity, timing, duration, or attribution, and it does not provide additional detail about how events were collected.

Safety counts should be interpreted alongside group sizes and the trial's observation and reporting procedures. A zero count for serious events is a description of what was recorded in this trial, not proof of zero risk. The registry record does not report enough detail to compare specific adverse-event types or to make broader safety conclusions.

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

The primary result describes the timing of a defined plasma glucose recovery event in a specific trial population: subjects with type 1 diabetes who experienced insulin-induced hypoglycemia and received one of the trial products. The median and confidence interval summarize estimated event timing, while the log-rank p-value assesses the registered dasiglucagon-versus-placebo comparison across event times. Together, these statistics describe the posted trial findings without conveying every participant's response.

The result does not show that all participants recovered by the median time, nor does it predict an individual participant's recovery. The endpoint required a specified rise from baseline without rescue intravenous glucose and was assessed during a limited post-dose window. Outcomes outside that definition or observation period are not represented by the primary summary.

The result also does not establish how the comparison would apply to populations, settings, doses, or treatment schedules that were not studied. The trial used single fixed subcutaneous doses and included a reference GlucaGen® group. The primary inferential comparison reported in the registry was against placebo, not a formal claim of equivalence or noninferiority against GlucaGen®.

A small p-value is not a measure of clinical importance, and the primary record does not provide a between-group effect estimate with a confidence interval. The median estimates offer context for typical timing, but do not show the full distribution of event times. The registered data therefore support a statistical description of earlier estimated recovery in the dasiglucagon group compared with placebo under the trial's definitions, not a universal statement about treatment effects or individual outcomes.

Finally, registry summaries do not replace full trial reporting. Details about missing data, censoring, multiplicity, model implementation, and participant flow are not reported in the registry record. Those details would help establish how robustly the estimates answer the intended question and how far the findings can be generalized.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint choice matters in clinical research. The primary outcome was not simply a glucose value at one scheduled time; it was the time until a prespecified recovery threshold was first met without rescue intravenous glucose. That formulation preserves timing information and leads naturally to Kaplan-Meier estimation and a log-rank comparison. The distinction between a time-to-event estimand and a single-time-point measurement is central to understanding both the reported median and the primary test.

The registry also illustrates that a test result and an effect estimate are not interchangeable. The log-rank p-value provides evidence about differences in event-time distributions under the test assumptions, while the group medians provide a summary of typical timing. Neither alone describes the full distribution or gives a between-group effect interval. Reading the statistics together helps avoid treating statistical significance as a measure of magnitude.

Another statistical lesson is the difference between a sponsor-reported model and a recalculation from summary statistics. An ANCOVA estimate may incorporate features of a model that cannot be recovered from group means and standard deviations alone. An unadjusted recalculation can be a useful check, but it answers a narrower question and cannot supersede a registered analysis without a clear methodological reason.

Finally, the record highlights the role of transparent reporting. Population definitions, censoring, missing-data handling, multiplicity, and sample-size rationale shape how confidently results can be interpreted. Where these details are not reported, statistical readers should distinguish what the results directly show from what remains uncertain, rather than filling gaps with assumptions.

15. 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 provides group-level primary summaries and a log-rank p-value, but not a between-group effect estimate with a confidence interval for time to recovery. Medians alone do not describe the shape of the event-time distributions, and the record does not provide participant-level times or detailed censoring information. The uncertainty around the full treatment contrast is therefore difficult to assess from the registry summary.

The primary population is defined as randomized patients who received at least one dose, but participant flow and exclusions are not reported in detail. Counts and reasons for missing observations, the treatment of missing data, and sensitivity analyses are also not reported in the registry record. This limits assessment of whether the analyzed groups fully reflect the randomized comparison.

Details of the randomization procedure, allocation concealment, and the practical implementation of quadruple masking are not reported. The registry also does not report the sample-size justification, interim analysis plan, or a multiplicity strategy for the numerous secondary outcomes. These omissions constrain evaluation of the design assumptions and the confirmatory status of secondary results.

The treatment regimen was a single fixed subcutaneous dose, and the primary endpoint was measured during the 0-45 minutes after dosing. The findings therefore describe that regimen and observation window rather than repeated dosing or longer-term outcomes. The record does not provide enough detail to determine how findings might extend beyond the enrolled subjects with type 1 diabetes and insulin-induced hypoglycemia. The secondary recalculations are based on posted summary statistics and cannot reproduce an adjusted analysis when its model details are unavailable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects — NCT03378635.
• Registry record last updated 2021-06-10; status last verified 2021-05.
• Results first posted 2021-05-10.
• 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.

19. Record Summary

NCT03378635 is a completed phase 3 randomized, double-blind, parallel trial of dasiglucagon, placebo, and GlucaGen® in subjects with type 1 diabetes and insulin-induced hypoglycemia. The registry reports enrollment of 170 and quadruple masking. Each group received a single fixed subcutaneous dose.

The primary outcome was time to plasma glucose recovery during the 0-45 minutes after dosing, defined as a rise of at least 20 mg/dL (1.1 mmol/L) from baseline without rescue intravenous glucose. The registry reports median recovery times of 10.0 minutes for dasiglucagon, 40.0 minutes for placebo, and 12.0 minutes for GlucaGen®. The registered dasiglucagon-versus-placebo log-rank analysis reports p < 0.001.

The record also lists secondary glucose, pharmacodynamic, and pharmacokinetic outcomes. It reports zero serious adverse events and zero deaths in each group. Further details about missing data, multiplicity, censoring, and the sample-size rationale are not reported in the registry record.