A Study to Measure Stomach Emptying in Overweight Non-diabetic and Diabetic Participants Using Tirzepatide: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Measure Stomach Emptying in Overweight Non-diabetic and Diabetic Participants Using Tirzepatide (NCT04407234), a na phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen.

2. Clinical Question

The study asks how acetaminophen exposure, used in the context of assessing stomach emptying, is characterized during tirzepatide treatment in overweight or obese participants without diabetes and in those with type 2 diabetes. Its primary endpoint is acetaminophen area under the concentration-time curve from dosing to the last time point with a measurable concentration, reported as a geometric mean with a 90% confidence interval.

3. Trial Design

This completed phase 1 study enrolled 36 participants and is described as a single-group study with allocation recorded as NA and masking recorded as none. It included overweight or obese participants without diabetes and overweight or obese participants with type 2 diabetes. The registry record does not describe a randomized treatment comparison; the two diabetes-status categories should therefore not be read as treatment and control arms.

The intervention description combines tirzepatide and acetaminophen. Participants received 5mg tirzepatide on Day 1 and Day 8, 10 mg on Day 15, 22 and 29, and 15 mg on Day 36 by subcutaneous administration. Oral acetaminophen was given on Day -1, Day 2 and Day 37. The registry describes the study as lasting about 13 weeks for each participant, including screening.

The recorded start date is 2020-09-15, the primary completion date is 2021-01-07, and the study status is completed. Those dates describe the study record, not the timing of individual participants’ assessments. The registry does not report a control group receiving a different treatment, nor does it describe masking. The design therefore provides pharmacokinetic observations under the listed dosing schedule, but does not by itself establish a randomized contrast between tirzepatide and another treatment.

The primary endpoint population is defined as randomized participants who received at least one dose of acetaminophen and had evaluable acetaminophen pharmacokinetic data. Although that wording includes “randomized participants,” the registry’s design fields identify allocation as NA and the study model as single group. Further details reconciling that wording 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 randomized participants who received at least one dose of acetaminophen and have evaluable acetaminophen PK data.

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: All randomized participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration [ AUC(0-tlast)] of Acetaminophen, measured over Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37 , Day 2 and Day 37.

The primary endpoint is acetaminophen AUC(0-tlast): the area under the concentration-time curve from time zero through the last time point at which acetaminophen concentration was measurable. It is expressed in nanograms*hours per milliliter (ng*h/mL), and the registry specifies a geometric mean with a 90% confidence interval. Concentration sampling is scheduled pre-dose and at 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, 24 and 36 hours post-dose on Day 1, Day 2 and Day 37.

As a general pharmacokinetic concept, an area under a concentration-time curve captures exposure across a sampling period, rather than describing concentration at only one moment. In this study, acetaminophen exposure is relevant to the stated interest in stomach emptying because the endpoint follows acetaminophen concentrations after dosing. The record does not give a direct stomach-emptying measurement or explain a specific conversion from acetaminophen exposure to a rate of emptying.

A geometric mean is a summary suited to measurements that are positive and may vary multiplicatively. A confidence interval conveys uncertainty around an estimate under the analysis assumptions; it is not a range containing every participant’s measurement. The record gives the endpoint definition and summary format, but numerical estimates and interval limits are not reported in the registry record. Consequently, the observed exposure and its precision cannot be described from the available endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited to the endpoint summary format, sampling schedule and analysis population wording. It identifies a geometric mean and a 90% confidence interval for acetaminophen AUC(0-tlast). It does not report the numerical estimate, interval limits, a detailed statistical analysis plan, or the model used to produce the summary. The concepts below explain the stated methods generally; they should not be taken as claims about unreported procedures in this study.

What does AUC(0-tlast) represent?

As a general pharmacokinetic measure, area under the concentration-time curve represents accumulated drug concentration across time. AUC(0-tlast) covers the period from time zero to the last measured time point with a measurable concentration. It is distinct from Cmax, which describes the maximum measured concentration, and from a single concentration at a specified sampling time. In this study the AUC is for acetaminophen, not a direct numeric measure of stomach emptying.

The registry lists pre-dose and post-dose sampling times on Day 1, Day 2 and Day 37. Such concentration measurements supply the time profile from which a pharmacokinetic exposure summary can be obtained. The available record does not give participant-level concentrations, the observed AUC values, or detail about handling measurements below the assay’s measurable range. Those details are not reported in the registry record.

Why report a geometric mean?

In general, pharmacokinetic measurements can be right-skewed: a smaller number of relatively high measurements can extend the upper tail. A geometric mean summarizes multiplicative rather than additive variation and is often useful for positive measurements with that pattern. It is commonly calculated by taking the mean on a logarithmic scale and transforming the result back to the original scale. The registry identifies the geometric mean as the summary, but does not describe the transformation or calculation procedure used for this analysis.

A geometric mean is not the same quantity as an arithmetic mean. It should be interpreted in light of the scale and distribution of the measurement, and it does not imply that every participant had a value near that summary. The record does not include a distribution plot, participant-level results or other descriptive statistics from which to evaluate the spread of individual AUC values.

How should a 90% confidence interval be understood?

Generally, a confidence interval describes uncertainty around an estimated quantity under a statistical procedure and its assumptions. With repeated use of the same procedure under those assumptions, intervals constructed in this way would cover the target quantity at the stated confidence level in the long run. A confidence interval does not mean that a stated fraction of individual participants’ measurements lie inside its limits. Nor does it describe the range of outcomes expected for a future participant.

The registry specifies a 90% confidence interval, but does not report its limits or explain the calculation method. Without those limits, readers cannot judge whether the estimate is precise or imprecise. The confidence level alone does not establish that an observed effect is important, nor does it provide evidence of a difference between groups.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model understates variability, standard errors and confidence intervals may be too small, making results appear more precise than they are. A method that accounts for extra variation can better reflect uncertainty when its assumptions are appropriate. The registry record does not report whether over-dispersion was assessed or whether any adjustment was used; no such procedure can be inferred from the endpoint summary format.

What can be inferred from the analysis population?

The primary endpoint population is described as all randomized participants who received at least one dose of acetaminophen and have evaluable acetaminophen pharmacokinetic data. This wording identifies conditions for inclusion in the endpoint analysis: participants must have received acetaminophen and have usable pharmacokinetic data. It does not specify how many participants met those conditions, how missing measurements were handled, or whether participants were excluded for other reasons.

The phrase “randomized participants” appears in the endpoint population wording, while the design fields identify allocation as NA and the model as single group. The registry record does not explain this difference in wording. It also does not give enough detail to establish whether a separate analysis population was used for each endpoint or participant category.

What does the design permit?

As a general design principle, a randomized control comparison can support an estimate of a treatment contrast when allocation and analysis are appropriate. The record describes no like-for-like randomized control comparison. Its pharmacokinetic summaries, if reported, would therefore describe measurements in the study population under the listed dosing conditions; they would not, on their own, quantify a randomized treatment effect against a control.

The registry does not report the statistical analysis plan, any interim analyses, a sample-size justification, or details of model diagnostics. The method statements are limited to what the record explicitly identifies and general explanations of the named statistical concepts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and twelve analyses. These counts indicate that several outcomes or analysis entries were registered, but the record does not describe how statistical multiplicity was handled. In general, assessing many outcomes or comparisons can raise the chance of observing at least one apparently notable result by chance. Common approaches include prespecifying a primary analysis or adjusting inference across a family of tests, but the registry does not say whether such an approach was used. It would be inappropriate to infer a correction, hierarchy or testing strategy from the number of listed analyses.

The primary outcome is identified as acetaminophen AUC(0-tlast), with a geometric mean and 90% confidence interval. Numerical results for that endpoint are not reported in the registry record. The record also lists secondary measures, including HbA1c by diabetic status and acetaminophen AUC(0-tlast) and Cmax by diabetic status. Their numerical results and any inferential comparisons are not reported in the registry record.

The stated primary analysis population requires receipt of at least one acetaminophen dose and evaluable acetaminophen pharmacokinetic data. The record does not report the number of participants with evaluable data, the amount or pattern of missing data, or the procedures used to address missing measurements. It does not explain whether a participant with incomplete sampling could contribute to an endpoint calculation, or how observations that could not be measured were treated.

The detailed statistical analysis plan, sample-size justification, and any interim analysis procedures are not reported in the registry record. Without those details and numerical endpoint results, readers cannot evaluate the prespecification of analyses, the impact of missingness, or the multiplicity implications of the listed outcomes.

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 registry reports safety counts separately for the Non-diabetic and T2DM groups. For serious adverse events, it records 0 affected among 18 at risk in each group. Deaths are also recorded as 0 in each group. For other adverse events, it records 16 affected among 18 at risk in each group. These figures describe the registry’s recorded counts; they do not establish that the event experience was identical across all participants or that the study was designed to compare safety between groups.

The serious-event terms list is empty in the registry record. That means no serious adverse-event terms are listed there; it does not provide descriptive detail about the other adverse events. The record does not give the event names, severity, timing, duration, relation to study treatment, or participant-level overlap between categories. The counts should not be added across groups, and the record does not establish whether a participant could contribute to more than one event category.

In general, adverse-event counts are descriptive safety information. A zero recorded count in a study group does not demonstrate that an event cannot occur, and counts from a single-group study do not supply a randomized treatment comparison. The posted safety figures should therefore be read as registry entries for the participants at risk, with the stated limitations on event detail and comparative interpretation.

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

The registry record describes a study of acetaminophen pharmacokinetics during a tirzepatide dosing schedule in overweight or obese participants without diabetes and participants with type 2 diabetes. It specifies the primary endpoint, its units, summary type, confidence level and sampling times. Those details make the intended measurement understandable, but they do not reveal the observed result: numerical estimates and confidence interval limits are not reported in the registry record.

Accordingly, the record does not establish the magnitude or precision of acetaminophen exposure in this study. It also does not provide numerical results that would allow readers to assess differences in pharmacokinetic measures by diabetic status. Since the study is described as a single group, with no randomized control comparison, it cannot be read as a randomized estimate of tirzepatide versus another treatment. The diabetes-status categories are not substitutes for such a comparison.

The endpoint concerns acetaminophen exposure over a sampling interval. While the study title and purpose concern stomach emptying, the primary outcome as registered is a pharmacokinetic summary, not a direct numerical stomach-emptying measurement. The registry record does not explain how the AUC result should be translated into a specific amount or rate of stomach emptying. A mechanistic or clinical conclusion cannot be derived from the endpoint definition alone.

The safety information indicates that no serious adverse events and no deaths were recorded in either group, while other adverse events were recorded. Those counts are descriptive and lack event-term detail. They do not demonstrate comparative safety or establish what would happen in a different population or treatment setting.

Overall, the record documents a study question and its measurement framework, but does not report the primary numerical outcome needed to interpret the observed pharmacokinetic result. It should not be used to claim that tirzepatide did or did not alter stomach emptying, or to draw conclusions about clinical benefit or harm.

13. Why This Trial Matters Statistically

This study is statistically interesting because its stated scientific interest—stomach emptying—is represented through a pharmacokinetic endpoint for acetaminophen. That distinction matters when interpreting the outcome. AUC(0-tlast) summarizes acetaminophen concentration over time; it is not itself a direct measure of stomach-emptying rate. Understanding what a measurement represents is essential before treating it as evidence about a broader physiological question.

The record also illustrates the importance of separating design structure from participant categories. It includes non-diabetic and T2DM groups, but describes a single-group model and no randomized control comparison. These categories may be relevant to describing or stratifying pharmacokinetic results, yet their presence does not create a randomized contrast. A reader must avoid interpreting group labels as treatment assignments.

Endpoint summaries should be interpreted with their uncertainty. The record specifies a geometric mean and 90% confidence interval, which identify the intended form of summary. Without the estimate and interval limits, however, neither magnitude nor precision can be assessed. The confidence level is not a substitute for the reported result, and the endpoint definition alone cannot support a substantive conclusion.

Finally, the difference between an endpoint population definition and the design fields merits attention. The population wording refers to randomized participants, while the record lists allocation as NA and the study model as single group. The registry does not explain this wording. Recognizing such gaps helps readers distinguish what is documented from what would require clarification, rather than filling in missing design or analysis details by assumption.

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 central limitation for interpreting the study is that numerical primary endpoint results are not reported in the registry record. Although the record specifies AUC(0-tlast), a geometric mean and a 90% confidence interval, it does not give the estimated value or interval limits. It therefore does not support a description of the observed acetaminophen exposure or its precision. Numerical secondary outcome results are also not reported in the registry record.

The study is described as single group, with allocation NA and no masking. There is no like-for-like randomized control comparison in the record. This limits causal interpretation and means the diabetes-status groups should not be treated as randomized treatment and control groups. The registry’s endpoint population wording refers to randomized participants, but the record does not explain how that wording relates to the design fields.

The endpoint is a pharmacokinetic measure of acetaminophen exposure, whereas the stated study interest concerns stomach emptying. The record does not report a direct stomach-emptying estimate or specify how acetaminophen AUC maps to a rate of emptying. The interpretation of AUC as a proxy therefore cannot be extended beyond what the record states.

Further limitations include the absence of a detailed statistical analysis plan, information about missing measurements, the number of participants with evaluable endpoint data, and the handling of incomplete pharmacokinetic profiles. The registry does not report a sample-size justification, interim analysis procedures, or a multiplicity strategy. Safety reporting also lacks serious-event terms and details for other adverse events. These omissions restrict assessment of the analysis, the precision of estimates, and the clinical context of the safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Measure Stomach Emptying in Overweight Non-diabetic and Diabetic Participants Using Tirzepatide — NCT04407234.
• Registry record last updated 2024-01-08; status last verified 2023-04.
• Results first posted 2024-01-08.
• 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

NCT04407234 is a completed phase 1, single-group study of tirzepatide and acetaminophen in overweight or obese participants without diabetes and participants with type 2 diabetes. The registry records enrollment of 36, no masking, and allocation as NA. Tirzepatide was administered subcutaneously on the listed schedule, with oral acetaminophen given on Day -1, Day 2 and Day 37.

The primary endpoint is acetaminophen AUC(0-tlast), summarized as a geometric mean with a 90% confidence interval. The record specifies sampling times but does not report numerical primary or secondary outcome results. Serious adverse events and deaths are recorded as 0 in each group; other adverse events are recorded in both groups. No serious-event terms are listed.

The registry does not describe a randomized control comparison, provide a detailed statistical analysis plan, or explain missing-data handling. The available record defines the study question and measurement framework but does not provide the numerical endpoint findings needed to evaluate the observed pharmacokinetic result.