A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function (NCT03482024), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]).

2. Clinical Question

The study is described as assessing how quickly tirzepatide enters the bloodstream and how long it takes the body to remove it in participants with impaired kidney function compared with healthy participants. The primary reported measure is AUC from time zero to tlast. It captures drug exposure over the observed concentration-measurement period; it is not itself a direct measure of clinical benefit or kidney outcomes.

The registry record reports group-level geometric means and geometric coefficients of variation for this endpoint. It does not report a statistical comparison analysis between each renal-function group and the healthy control group. Accordingly, the results support a descriptive account of the posted pharmacokinetic values, but do not establish whether observed differences are statistically distinguishable or attributable to renal function.

3. Trial Design

This is a completed phase 1 randomized, open-label, parallel-group study sponsored by Eli Lilly and Company. The registry record lists an enrollment of 45. The study started on 2018-03-30, and primary completion was recorded on 2019-08-19.

Five groups are described: healthy participants with normal renal function, and participants with mild, moderate, or severe renal impairment or ESRD. Each group received tirzepatide 5 mg by subcutaneous administration. The healthy group is identified as the control, but it also received the study drug. Thus, the design compares pharmacokinetic results among participants with different renal-function categories after exposure to tirzepatide; it does not compare the drug with placebo or no treatment.

Randomization is recorded, but the registry record does not report the randomization procedure, allocation ratio, or how participants were assigned to the renal-function categories. Masking is recorded as none, so the study was open label. The parallel model indicates separate groups rather than a crossover description in the registry record. Further details about the conduct of the study, including the protocol rationale for the design, are not reported in the registry record.

The primary endpoint was AUC from time zero to tlast, with concentration measurements scheduled predose and at 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, and 336h postdose. The endpoint population included participants who received at least one dose and had evaluable pharmacokinetic data. The number included in that endpoint differs by group, as reported in the results: 13.0 for healthy controls, 8.0 for mild renal impairment, 8.0 for moderate renal impairment, 6.0 for severe renal impairment, and 8.0 for ESRD.

The record reports three outcome measures, but it does not report secondary posted results. No inferential analyses are listed for the posted outcome results. The protocol's sample-size justification and any planned interim analyses 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 participants who received at least one dose of study drug and had evaluable 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.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide From Time Zero to Tlast (AUC[0-tlast]), measured over Predose, 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, 336h postdose.

The primary endpoint is the area under the concentration-versus-time curve for tirzepatide from time zero to tlast, reported in nanogram*hour per Millilitre (ng*h/mL). AUC represents the accumulated concentration over the observed measurement interval: it incorporates both the concentration of drug in the blood and how that concentration changes over time. The tlast boundary means the measure ends at the last time point used for the participant's evaluable concentration profile; it is not a measure of exposure beyond that observed interval.

Pharmacokinetic AUC is used to describe drug exposure. In a study organized by renal-function category, comparing this measure across groups can help characterize whether the reported exposure profiles differ. It does not, by itself, establish why any difference occurred, whether it is statistically reliable, or whether it implies a difference in clinical outcomes.

The registry record reports geometric means and geometric coefficients of variation. The posted geometric mean AUC values are 78400.0 for healthy controls, 81900.0 for mild renal impairment, 98300.0 for moderate renal impairment, 81200.0 for severe renal impairment, and 88500.0 for ESRD. The corresponding geometric coefficients of variation are 24.0, 36.0, 32.0, 9.0, and 14.0. These are descriptive group summaries; no confidence intervals or group-comparison tests are reported for the primary endpoint.

Concentration measurements were scheduled predose and at 8hours(h), 12h, 24h, 48h, 72h, 96h, 168h, and 336h postdose. The registry record does not provide participant-level concentration profiles or further detail about how tlast was determined.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a continuous pharmacokinetic measure, summarized as a geometric mean with a geometric coefficient of variation. There are no reported inferential analyses for the primary endpoint. The descriptions below explain the statistical concepts relevant to interpreting these summaries; they are general explanations, not claims about additional procedures used in this study.

What does AUC measure?

In general, an area under a concentration-versus-time curve combines concentration information across time into a summary of exposure over a specified interval. AUC from time zero to tlast uses the portion of the observed profile through its last included time point. The registry lists predose and postdose measurement times, ending at 336h postdose. AUC is useful because a single concentration measurement can miss how the concentration profile changes across the observation period. It remains an exposure measure, not a direct measure of a clinical outcome.

Why report a geometric mean?

In general, a geometric mean summarizes positive measurements on a multiplicative scale. It is calculated from the mean of the logarithms of the observations and then expressed back on the original scale. This can be appropriate for pharmacokinetic measurements when values are naturally interpreted through proportional rather than additive variation. The registry record identifies the reported parameter as a geometric mean, but does not state the detailed calculation procedure or any data transformations used in the analysis.

What does the geometric coefficient of variation convey?

In general, a coefficient of variation expresses variability relative to the scale of the measurements. The geometric version describes dispersion for data treated on a logarithmic, multiplicative scale. It is not a confidence interval and does not indicate the precision of a group mean by itself. The reported values differ among the groups, so the degree of within-group variability is not uniform in the posted summaries. Without participant-level data or uncertainty intervals, the extent to which individual distributions overlap cannot be determined from the means and dispersion summaries alone.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure. For a contrast between groups, an interval can show the direction and precision of the estimated difference or ratio, depending on the scale and model. The registry record does not report confidence intervals for the group means or for comparisons. Therefore, the precision of the differences between the posted geometric means cannot be assessed from the reported summaries alone.

Why does over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model would expect under its assumptions. When a model underestimates variability, standard errors can be too small and uncertainty can appear narrower than warranted. The registry record gives geometric coefficients of variation, but does not report a fitted comparison model or diagnostics for over-dispersion. It would therefore be inappropriate to assert that over-dispersion was present or that a particular adjustment was used. More broadly, any inferential analysis should account for the actual distribution and variability of pharmacokinetic measurements rather than relying on a model assumption without assessment.

What does an unadjusted comparison mean?

In general, an unadjusted comparison uses the observed groups without accounting for other variables through a model. An adjusted analysis can account for prespecified factors, but its interpretation depends on the chosen model, the variables included, and the data available. No comparisons, adjusted or unadjusted, are reported in the registry record. There is also no reported analysis plan specifying covariate adjustment, transformations, or the inferential scale for comparisons. Consequently, no adjusted effect estimate or recalculated comparison should be inferred from the posted group summaries.

How should group sizes affect interpretation?

In general, the amount of information available for estimating a group summary depends in part on the number of evaluable observations and their variability. Smaller groups can yield less precise estimates, although precision also depends on the spread and the analysis method. The endpoint counts are 13.0, 8.0, 8.0, 6.0, and 8.0 across the healthy control, mild, moderate, severe, and ESRD groups, respectively. The registry record does not provide confidence intervals, so it does not quantify the uncertainty associated with each estimate. These counts describe the endpoint population and should not be conflated with the separate safety at-risk counts.

For planning, a sample-size calculation requires assumptions about a target effect, variability, significance level, allocation, and analysis method. The registry record does not report its sample-size justification or planning assumptions. Planning calculations based on observed effects, if presented separately, would be illustrations under stated assumptions and would not represent observed power or establish that the study was adequately powered for a particular comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures but reports no secondary posted results. It identifies AUC from time zero to tlast as the primary outcome measure. It does not report a multiplicity strategy, such as a hierarchy among endpoints or an adjustment for multiple comparisons. Because no inferential group comparisons are posted, there are no reported p-values for which the treatment of multiplicity can be assessed. The protocol's approach to multiple testing is not reported in the registry record.

The primary endpoint population is defined as participants who received at least one dose of study drug and had evaluable PK data. The posted endpoint counts are 13.0 for healthy controls, 8.0 for mild renal impairment, 8.0 for moderate renal impairment, 6.0 for severe renal impairment, and 8.0 for ESRD. The registry record does not explain why the number of evaluable participants differs from group to group, describe missing concentration measurements, or state how missing PK observations were handled. It also does not report whether any participants were excluded from the endpoint analysis after dosing or how evaluability was determined.

These omissions matter because the reported summaries represent evaluable PK data, not necessarily all participants enrolled or assigned to a group. If missingness is related to measured exposure or participant characteristics, a complete-case summary may not represent the full group in the same way as if data were missing for unrelated reasons. The registry record does not provide enough information to assess that possibility.

Safety at-risk counts are reported separately from the endpoint counts. These populations should not be treated as interchangeable: the registry record lists different counts for some groups. No analysis population beyond the stated PK population and the adverse-event at-risk groups is described. Details about analysis-set definitions, missing-data sensitivity analyses, and the statistical plan are not reported in the registry record.

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 record reports zero serious adverse events in each group. The corresponding at-risk counts were 14 for healthy controls, 8 for mild renal impairment, 8 for moderate renal impairment, 7 for severe renal impairment, and 8 for ESRD. Deaths are recorded as zero in every group.

Other adverse events were reported for 1 participant in the control group, 4 in mild renal impairment, 3 in moderate renal impairment, 3 in severe renal impairment, and 3 in ESRD. These are counts, not percentages, and the registry record does not provide event-level descriptions in the serious-event terms list. The zero serious-event counts mean that no serious adverse events were recorded in these listed groups; they do not establish that the risk of serious events is absent. The registry record does not report inferential comparisons or uncertainty intervals for the safety counts.

Safety counts should be read using their own at-risk denominators. They do not match all of the reported PK endpoint counts, and the registry record does not explain the differences. These safety summaries are descriptive and do not support conclusions about comparative safety between renal-function categories.

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

The posted results establish that the registry reports group-level geometric mean AUC values after tirzepatide 5 mg administration in healthy controls and participants in renal-function categories. The reported means are 78400.0 for healthy controls, 81900.0 for mild renal impairment, 98300.0 for moderate renal impairment, 81200.0 for severe renal impairment, and 88500.0 for ESRD. The geometric coefficients of variation are also reported, showing that the degree of dispersion differs across groups. These are descriptive findings about the pharmacokinetic endpoint in the evaluable population.

The values do not, by themselves, show whether the groups differ beyond what could plausibly arise from sampling variation. The registry record includes no comparison estimates, p-values, or confidence intervals for group contrasts. A reader therefore cannot assess inferential precision or determine whether the descriptive differences meet any statistical criterion. Nor can the posted summaries determine the clinical or pharmacological importance of those differences.

This study compares renal-function categories among participants who all received tirzepatide. It does not provide a drug-versus-placebo comparison, and the endpoint is exposure rather than a clinical outcome. The results cannot establish a treatment effect on renal function, patient symptoms, or health outcomes. They also do not, on their own, establish a dosing recommendation or justify a change in clinical practice.

The reported group summaries apply to participants with evaluable PK data after at least one dose, as specified in the endpoint population. They may not represent every participant enrolled. The registry record does not describe missing-data handling, the details of assignment, or the rationale for the planned enrollment. These gaps constrain assessment of representativeness, precision, and the methods used to reach any broader conclusion.

In short, the registry provides a descriptive pharmacokinetic profile across the listed groups and records no serious adverse events in the reported safety groups. It does not provide the comparative statistical evidence or clinical outcomes needed to draw stronger conclusions about differences, their causes, or their implications.

13. Why This Trial Matters Statistically

This trial addresses a statistical question about how a pharmacokinetic exposure measure is distributed across renal-function categories. Such a question differs from a conventional efficacy comparison: all groups received tirzepatide, and the principal contrast is between participant groups defined by renal status. That makes clear reporting of the group definitions, endpoint population, measurement schedule, and summary scale especially important.

The use of a geometric mean and geometric coefficient of variation is relevant because pharmacokinetic measurements are often interpreted on a multiplicative scale. Reporting both a central summary and a dispersion measure gives readers more context than a mean alone. At the same time, these summaries cannot replace confidence intervals or model-based contrasts when the aim is to quantify between-group uncertainty. The registry record reports descriptive values but no inferential comparisons, so its evidence is limited to the observed summaries.

Unequal endpoint counts and different levels of reported variability also matter for interpretation. The posted group summaries represent varying amounts of evaluable data, and the registry does not explain the count differences or report uncertainty intervals. A well-described analysis population and missing-data approach would help readers understand how the available records relate to the enrolled participants.

The study is statistically informative as a registry record of exposure measurements across the stated renal-function categories, but its contribution is bounded by the reported information. The absence of posted comparative analyses means readers cannot judge statistical precision or distinguish a descriptive difference from an uncertain one. This is an important distinction in pharmacokinetic research, where numerical separation between group summaries is not equivalent to evidence of a reliable or clinically meaningful difference.

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 endpoint results are descriptive. The registry record reports no inferential comparisons between renal-function groups and healthy controls, and no confidence intervals or p-values for the primary outcome. Consequently, the precision of group differences cannot be evaluated from the posted results.

The registry record does not report the randomization procedure, allocation ratio, or how renal-function categories were determined. Although the study is listed as randomized, the record does not explain what was randomized. It also does not provide detail about the analysis model, covariate adjustment, endpoint calculation procedure, or diagnostic checks. These omissions limit assessment of how the reported group estimates were generated.

The endpoint population includes participants with at least one dose and evaluable PK data. Endpoint counts vary among groups, and the registry record does not state why data were not evaluable for all participants, how missing observations were handled, or whether sensitivity analyses were performed. The safety at-risk counts are also different from some endpoint counts, with no further explanation.

The record lists three outcome measures but reports no secondary posted results, and it does not describe a multiplicity plan. Sample-size justification and interim-analysis plans are not reported in the registry record. There is also no posted participant-level information, concentration profile, or uncertainty estimate that would permit independent examination of the group summaries. These limitations make the results useful as descriptive registry evidence but constrain conclusions about comparative precision, missingness, and broader implications.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Tirzepatide (LY3298176) in Participants With Impaired Kidney Function — NCT03482024.
• Registry record last updated 2023-03-23; status last verified 2022-06-01.
• Results first posted 2023-03-23.
• 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

NCT03482024 is a completed phase 1 randomized, open-label, parallel-group study of tirzepatide sponsored by Eli Lilly and Company. It enrolled 45 participants and compared pharmacokinetic results across healthy controls and groups with mild, moderate, or severe renal impairment or ESRD. All groups received tirzepatide 5 mg subcutaneously.

The primary endpoint was AUC from time zero to tlast, summarized by geometric means and geometric coefficients of variation among participants who received at least one dose and had evaluable PK data. The record reports group-level endpoint values but no inferential comparisons or uncertainty intervals. It also records zero serious adverse events and zero deaths in each safety group, with other adverse-event counts reported by group.

The posted findings describe exposure and safety counts in the registry record. They do not establish comparative statistical significance, clinical effects, or implications for treatment.