The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans (NCT04461015), a randomized phase 3 study. The primary outcome is Endogenous Glucose Production (EGP).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, unmasked crossover study and lists its phase as PHASE3. Enrollment is 12, the condition is healthy, and the status is completed. The record gives a start date of 2020-10-14 and a primary completion date of 2021-07-30. These are registry-record details; they do not provide evidence about the outcome of the comparison.

In a crossover design, participants receive more than one study condition in a planned sequence, so comparisons may be made within participants. Here, the listed conditions are an insulin infusion of 0.4mU/Kg/Min and an infusion of 0.8mU/Kg/Min during a euglycemic clamp. The intervention descriptions list both orderings, with a withdrawal period between the studies. The registry record does not report the duration or conduct of that period, or whether all enrolled participants completed both conditions.

Randomization indicates that assignment to the listed sequence was randomized. Masking is recorded as none, so the record does not describe blinding of participants or study personnel. It does not report how randomization was generated, whether allocation was concealed, or how the study handled possible effects of treatment order or period. Those details should not be inferred from the crossover label alone.

The primary outcome is a continuous measure reported as a mean with standard error. It is based on tracer measurement and expressed per kg lean body mass. Measurements are specified at 90, 180 and 270 minutes in each study condition. The record lists one outcome measure and no analyses. It does not report participant flow, analysis populations, numerical outcome estimates, or a statistical analysis 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: The study is a cross-over study - subjects participated in both arms

Overall Study

Reasons for not completing this period:

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 Endogenous Glucose Production (EGP), measured over It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints.

The primary endpoint is endogenous glucose production (EGP), described as a tracer-based measurement expressed per kg lean body mass. Its stated unit is umol/kg/min. The measurement is intended to quantify the body's glucose production, which relates to the study's stated interest in metabolism and the body's ability to make glucose. The record identifies EGP as the outcome for comparing the two insulin infusion conditions.

Measurements are specified at 90, 180 and 270 minutes for the 0.4mU insulin study, with comparison to values at the same time points in the 0.8mU study. That timing makes the time-specific values relevant: an average across time points would answer a different question from comparisons at each stated time. The registry record does not report the values at any of these time points, the size or direction of a difference, or a confidence interval.

The measure is characterized as a mean of a continuous outcome, with standard error as the dispersion measure. A mean describes the central value of measurements; a standard error describes the uncertainty around an estimated mean. Neither the mean nor its standard error is reported as a numerical result in the registry record. The record also does not specify how tracer measurements were processed, beyond identifying the tracer-based measurement and its expression per kg lean body mass.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous and is specified as a mean with standard error. In general, a mean gives a summary of the central level of a continuous measurement. A standard error describes the sampling uncertainty in an estimated mean; it is not a description of the spread of individual measurements. A standard deviation, by contrast, describes participant-level variability. The registry record names standard error as the dispersion measure but does not provide numerical means or standard errors for EGP.

A confidence interval is a general way to express uncertainty around an estimated effect. It gives a range of values compatible with the data and the method used, rather than a guarantee that the true value lies inside the interval. For this comparison, an informative report would ordinarily identify the contrast between conditions at the relevant time point or points, together with its uncertainty. The registry record does not report a contrast or confidence interval, so precision cannot be judged. A p-value alone, if one were reported, would not describe the magnitude or precision of the effect.

How does crossover structure affect the comparison?

In general, crossover studies compare conditions received by the same participants. An analysis can use the within-participant differences, which may remove some variation due to characteristics that remain stable within a participant. This is different from treating observations from the two conditions as if they came from unrelated groups. The registry record identifies a crossover model and randomized sequences, but does not report whether the primary analysis used a paired method or a model accounting for participant, sequence, or period.

Crossover comparisons also require attention to order and time. A period effect is a change associated with when a condition is received, rather than with the condition itself. Carryover refers to an effect of an earlier condition that persists into a later period. A withdrawal period is listed between the study conditions, but its duration and intended role are not reported in the registry record. No analysis of period, sequence, or carryover is reported, so none should be assumed.

Why do the measurement times matter?

The outcome is specified at 90, 180 and 270 minutes. Each time point represents a distinct measurement occasion, and a difference at one time need not be the same as a difference at another. General analysis choices include reporting time-specific contrasts, modeling change across time, or selecting a prespecified time point as the primary comparison. These approaches answer different questions. The registry record does not state which approach was planned or used, and the numerical measurements are not reported.

When more than one statistical comparison is made, multiplicity is a general concern. Repeated testing can make a nominal p-value less informative about the overall evidence unless the testing strategy is specified. Possible strategies include defining one primary comparison in advance or adjusting inference across a family of tests. The registry record does not report whether time-specific tests were conducted or whether any adjustment was made. It is not possible to infer a multiplicity strategy from the list of measurement times alone.

What does the planning approach describe?

The stated planning assumptions describe an illustration using an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, a sample-size calculation estimates how many participants per arm would be needed under specified assumptions to detect a target effect with a chosen power. Such calculations depend on the effect size, variability, allocation, and test assumptions. A planning illustration is not an observed result, and it is not observed power. In this case, the registry record does not report the numerical observed effect or any resulting planning headcounts. The assumptions also are not a substitute for a protocol or a sample-size justification; the trial's own justification is not reported in the registry record.

There are no reported primary-outcome analyses in the record. That limits statistical interpretation beyond the general description of the endpoint and design. The record does not provide a model specification, a missing-data method, an analysis population, or a rule for handling repeated measurements. It also does not report whether analyses were adjusted for other variables. Without those details and the outcome estimates, no recalculation from posted summary statistics is possible, and no claim about statistical significance or precision can be made.

10. Multiplicity, Missing Data and Analysis Populations

The outcome is scheduled at 90, 180 and 270 minutes, so an analysis could involve several time-specific comparisons. In general, evaluating multiple comparisons raises the possibility of chance findings when results are interpreted one test at a time. A prespecified primary time point, a defined family of tests, or an adjustment method can clarify how the evidence should be interpreted. The registry record does not report a multiplicity plan, whether time points were analyzed separately, or which comparison would govern the primary inference.

The record lists one outcome measure and zero analyses. It therefore provides no reported statistical results for assessing whether multiplicity affected interpretation. It also does not report a statistical analysis plan or distinguish planned from exploratory analyses. No method for combining the time points is reported.

Missing-data handling is not reported in the registry record. The record does not state whether any EGP measurements were unavailable, how incomplete crossover periods were handled, or whether an analysis required observations from both conditions. The enrollment entry does not establish the number contributing to each endpoint comparison. The analysis population is also not reported, including whether an intention-to-treat, per-protocol, or other population was used.

These omissions matter because missing measurements and analysis-population choices can affect both the estimate and its uncertainty. In a crossover study, incomplete participation in one condition can also affect the set of within-participant comparisons. These are general considerations, not claims about what occurred in this study. The registry record does not give enough information to determine the extent or handling of any missing data.

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.

Most frequent non-serious adverse event terms

The adverse-event entries list 12 at risk in each condition group. The 0.4 Events group reports 0 serious adverse events, 1 other adverse event, and 0 deaths. The 0.8 Events group reports 0 serious adverse events, 2 other adverse events, and 0 deaths. These are the counts recorded for the listed groups; they do not by themselves establish the causes or clinical importance of the events.

Because the study is a crossover, the condition groups should not automatically be interpreted as separate parallel sets of participants. The registry record does not clarify whether adverse events were counted by participant, event occurrence, or study period, and it does not report how repeat events were handled. The group entries therefore should not be used to infer a total number of distinct participants with events.

No serious-event terms are listed. The record does not provide event descriptions for the other adverse events, severity, timing, relatedness to the intervention, or the method for collecting events. These counts alone cannot establish a comparative safety profile. They describe the registry entries without explaining why events occurred or whether the conditions caused them.

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

The record describes a randomized crossover comparison of two insulin infusion conditions in healthy participants, with EGP as the primary outcome. It specifies tracer-based measurement at 90, 180 and 270 minutes and describes the result as a mean with standard error. These details define the intended measurement and comparison, but they are not outcome findings.

The numerical EGP values and statistical analyses are not reported in the registry record. Therefore, the record does not establish the direction or size of any difference between conditions, how precisely a difference was estimated, or whether a statistical test supported a particular inference. It also does not establish that the conditions were equivalent or that there was no effect. Those conclusions require results and an analysis that are not reported.

The study's stated purpose concerns the relative importance of insulin secretion and glucagon in regulating metabolism and the body's ability to make glucose. The listed interventions specify insulin infusion conditions. The registry record does not describe the details of any glucagon manipulation or provide results that quantify the separate contributions of insulin and glucagon. The title and stated purpose should not be treated as evidence for a particular physiological finding.

The registry entry identifies enrollment of 12 and completed status. It does not report how many participants completed both study conditions or contributed to the primary endpoint analysis. Nor does it give details sufficient to assess how well the findings, if reported elsewhere, would apply beyond the recorded healthy population. The listed adverse-event counts are limited descriptions and do not resolve the efficacy question.

In short, the record establishes the study question, broad design, endpoint, measurement times, and some event counts. It does not report the primary outcome results needed to answer the comparison statistically. Interpretation should remain limited to those design and reporting details.

13. Why This Trial Matters Statistically

This study illustrates why a clinical question and a statistical result are different things. The registry record defines a comparison, specifies an endpoint, and names the time points, but provides no numerical EGP findings or analyses. A clear design description helps identify what would be estimated; without estimates and uncertainty, readers cannot judge the observed effect or its precision.

The crossover model makes the unit of comparison important. In general, measurements from the same participant are related, and an analysis should account for that dependence rather than assume that all observations are independent. The record identifies the crossover design but does not report the analysis method. This distinction is important when assessing whether a statistical result would match the design.

Repeated outcome times also raise a question about which comparison is primary and how multiple tests are handled. Those choices affect interpretation, not merely presentation. The registry record lists the measurement schedule but does not describe a multiplicity strategy or the primary statistical contrast. A reader should not infer that one time point was more important, or that several results were adjusted, without documentation.

Finally, the distinction between a planning calculation and a study finding is central. The stated sample-size assumptions refer to an illustrative calculation based on an observed effect; they are not the trial's own design justification and do not show what the trial found. Planning assumptions cannot replace an observed estimate and its uncertainty. The record's lack of outcome analysis leaves the central statistical question unanswered, regardless of the study's completed status.

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.

The primary limitation for interpretation is that numerical results for EGP are not reported in the registry record. There are no condition-specific means, contrasts, standard errors, confidence intervals, or p-values. The registry record lists zero analyses, so there is no reported statistical estimate to evaluate. This prevents assessment of effect direction, magnitude, precision, or compatibility with a null difference.

Important design and analysis details are also absent. The record does not report the randomization method, allocation concealment, details of the withdrawal period, participant flow, or completion of both study conditions. It does not describe the statistical model, handling of period or sequence, a missing-data approach, or the analysis population. These matters are especially relevant to interpreting a crossover comparison, but no assumptions about how they were handled are warranted.

The primary endpoint is specified at several time points, but the record does not identify a single time point as the primary inferential contrast or state how multiplicity was addressed. It gives no analysis plan and does not report whether the listed times were analyzed separately or jointly. It also does not provide details on tracer processing beyond describing the measurement as tracer-based and expressed per kg lean body mass.

The record identifies a healthy population and enrollment of 12, but gives no further participant characteristics or endpoint-specific denominators. It does not report details of glucagon procedures despite the study title and stated purpose. Safety reporting is limited to event counts, without descriptions, severity, timing, or relatedness. These limitations restrict what can be concluded from this registry record; they do not establish that any particular methodological problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans — NCT04461015.
• Registry record last updated 2022-06-21; status last verified 2022-05.
• Results first posted 2022-06-21.
• 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 record describes a completed, randomized, unmasked crossover study listed as PHASE3, with enrollment of 12 and a healthy population. The study compares insulin infusion conditions of 0.4mU/Kg/Min and 0.8mU/Kg/Min during a euglycemic clamp, with a withdrawal period in the listed sequences.

The primary endpoint is tracer-based endogenous glucose production, expressed per kg lean body mass and reported as a mean with standard error. Measurements are specified at 90, 180 and 270 minutes. The record lists one outcome measure and zero analyses; numerical primary-outcome results are not reported.

Adverse-event entries report 0 serious adverse events in each listed group, 1 and 2 other adverse events, and 0 deaths in each group. Event details and the primary outcome analysis are not reported in the registry record.