A Study of LY3493269 in Participants With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3493269 in Participants With Type 2 Diabetes (NCT04515576), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, parallel-group Phase 1 study of LY3493269 in participants with type 2 diabetes. The registry record lists enrollment of 56 and identifies Eli Lilly and Company as the sponsor. The study is marked completed. Its recorded start date is 2020-08-25, and its primary completion date is 2021-03-09.

There were six treatment groups: placebo; 1.5 mg dulaglutide; 0.3 mg LY3493269; 1 mg LY3493269; escalating LY3493269 doses of 0.75/1.5/3 mg; and escalating doses of 1.5/3/4/5 mg. The fixed LY3493269 dose groups received weekly doses for 4 weeks. In the escalating groups, doses increased according to the schedules recorded for each group. Dulaglutide and placebo were also administered subcutaneously once weekly for 4 weeks.

The stated purpose was to assess side effects and measure concentrations of LY3493269 in blood. Secondary outcomes include pharmacokinetic measures—area under the concentration-versus-time curve from time zero to 168 hours postdose and maximum observed concentration—and change from baseline to Day 29 in fasting plasma glucose. The primary safety endpoint covers baseline through final follow-up at Day 57. The study summary says participation could last up to approximately 16 weeks, with up to 11 visits. The registry record does not report allocation ratios or further details of how randomization and masking were implemented.

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.

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 participants who received at least one dose of study drug.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration, measured over Baseline through final follow-up at Day 57.

The primary endpoint is the number of participants with one or more treatment-emergent adverse events or serious adverse events that the investigator considered related to study drug administration. The observation period runs from baseline through final follow-up at Day 57. The specified population is participants who received at least one dose of study drug.

A treatment-emergent adverse event is an untoward medical occurrence that begins during the defined treatment period after being absent before treatment, or that worsens relative to the pretreatment state. The registry definition notes that such an event does not necessarily have a causal relationship with treatment. A serious adverse event is defined by outcomes such as death, a life-threatening event, inpatient hospitalization or its prolongation, persistent disability, a congenital anomaly or birth defect, or another situation judged serious using medical or scientific judgment.

Counting participants with at least one event is a way to summarize how many people experienced an event meeting the endpoint definition during the observation period. It does not convey the number of events per participant, their duration, or their severity beyond the serious-event classification. The registry record says that adverse events regardless of causality are reported separately. Those broader counts should not be treated as identical to the primary endpoint, which requires investigator attribution as related.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count of participants with an event represent?

For a binary safety outcome, each participant is classified according to whether the defined event occurred during the specified observation period. The result is a count of participants with the event, rather than a count of every event episode. A participant with repeated events may still contribute only once to a measure defined as having one or more events. This distinction matters because participant counts do not show how often events recurred or how long they lasted.

In this study, the primary endpoint concerns participants with one or more treatment-emergent adverse events or serious adverse events considered by the investigator to be related to study drug administration. The endpoint’s window is baseline through final follow-up at Day 57. The posted adverse-event data also distinguish serious events from other events, but the broader summaries are described as regardless of causality. Thus, endpoint-specific attribution and the broader event summaries answer different questions.

Why is a group size relevant to interpreting a count?

General statistical explanation: an event count is easier to interpret when considered with the number of participants observed in that group. Even then, a small group can provide imprecise information about the underlying frequency of an event. A count of zero means no event was recorded in the observed group during the stated window; it does not show that the event is impossible or that its underlying frequency is zero. Uncommon events can remain uncertain when the observed groups are small.

The registry record gives numbers at risk for the serious- and other-event summaries. It does not report confidence intervals for those summaries in the registry record, so the precision of any underlying event frequency cannot be quantified. Comparisons based only on counts can also mislead when group sizes differ. No new rates or between-group differences are calculated in this interpretation.

What can randomization and masking contribute?

General statistical explanation: random allocation is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. Masking can reduce the influence of treatment knowledge on participant reports, clinical assessments, or decisions. These design features do not ensure that every group has the same characteristics, and they do not remove uncertainty in a small study. The registry record identifies the trial as randomized and double-masked but does not report the randomization procedure, allocation ratio, masking procedures, or an assessment of whether masking was maintained.

What analysis was reported?

The registry record describes the endpoint and the analysis population as participants who received at least one dose of study drug. It does not report a statistical model, adjustment strategy, confidence interval, hypothesis test, or treatment contrast for the primary endpoint in the registry record for this analysis. The record indicates no listed analyses. As a result, interpretation should remain descriptive rather than implying a formal comparative test.

General statistical explanation: an inferential comparison requires a defined contrast and an analysis method appropriate to the outcome and design. For a binary endpoint, that method might estimate a difference or ratio between groups, with uncertainty described by an interval. Such quantities cannot be reconstructed responsibly without the relevant analysis details and outcome data for the endpoint as defined. The posted counts for adverse events regardless of causality are not a substitute for those missing endpoint-specific results.

How should dose schedules be considered?

The LY3493269 groups include fixed-dose and escalating-dose schedules, while placebo and dulaglutide were administered weekly for 4 weeks. The schedules therefore differ in the doses received over time. A simple ordering of the event counts by group would not, by itself, isolate the effect of dose: group size, schedule, random variation, and other factors can all affect observed counts. The registry record does not report a dose-response model or a statistical comparison across dose groups.

General statistical explanation: dose-response analyses require a defined way to represent dose exposure and an analysis plan that accounts for the study design. For escalating schedules, the dose is not a single constant amount throughout treatment. No dose-response conclusion follows merely from comparing the group-level counts. The pharmacokinetic and pharmacodynamic outcomes may provide other kinds of information, but their numerical results are not reported in the registry record for this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists several secondary outcomes in addition to the primary safety endpoint: pharmacokinetic area under the concentration-versus-time curve from time zero to 168 hours postdose, maximum observed LY3493269 concentration, and change from baseline to Day 29 in fasting plasma glucose. It also reports four outcome measures overall. These outcomes address different aspects of drug exposure and response, rather than representing interchangeable measures of the same question.

Multiplicity arises when several outcomes, treatment groups, time points, or statistical comparisons are assessed. General statistical explanation: the more opportunities there are to identify a result as noteworthy, the more important it is to specify in advance which questions are primary and how additional comparisons will be interpreted. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a detailed statistical analysis plan. It is therefore not possible to determine from this record whether or how multiplicity was addressed.

The record does not report a missing-data method, the amount or pattern of missing outcome data, or how incomplete follow-up was handled. The primary safety population is defined as participants who received at least one dose, but the record does not provide a detailed account of exclusions or outcome-specific analysis populations. It also does not report whether participants were analyzed according to randomized assignment or according to treatment received.

The registry record does not identify interim analyses, sample-size justification, or a formal hypothesis-testing strategy. These omissions do not establish that such procedures were absent from all study documentation; they mean they are not reported in the registry record. Consequently, the reported event counts should be read as descriptive results, without assuming an unreported adjustment, imputation procedure, or inferential framework.

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 serious adverse-event summary reports zero affected participants in each group, with numbers at risk of 7 for placebo, 8 for 1.5 mg dulaglutide, 8 for 0.3 mg LY3493269, 8 for 1 mg LY3493269, 11 for 0.75/1.5/3 mg LY3493269, and 14 for 1.5/3/4/5 mg LY3493269. Deaths are reported as zero in every group. These are observed counts over the registry’s adverse-event reporting period; they do not prove that serious adverse events are impossible.

The “other” adverse-event counts are distinct from the serious-event counts and include events regardless of causality. The reported numbers of participants affected are 2, 5, 5, 7, 11, and 13 across the groups in the order. They should not be read as numbers of events, because the summary counts participants affected. Nor do they show whether an investigator judged an event to be related to study drug.

The primary endpoint specifically requires investigator consideration of a treatment-emergent or serious adverse event as related. The adverse-event counts alone do not provide that endpoint result. The registry record does not report the related-event counts by group in the registry record for this analysis.

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

The registry record offers a description of the study design and a snapshot of adverse-event counts across placebo, dulaglutide, and LY3493269 groups. In the posted safety summaries, no serious adverse events or deaths are reported in any group. Other adverse events are reported across all groups. These observations describe what was recorded in this study, not the full range of possible outcomes under other circumstances.

The results do not establish that LY3493269 is safe or unsafe, and they do not show whether it is better or worse than placebo or dulaglutide. The available adverse-event summaries do not provide a group-level result for the primary endpoint’s investigator-related events. Nor do the registry entries available for this analysis provide numerical results for the pharmacokinetic or pharmacodynamic outcomes. Conclusions about those outcomes cannot be drawn from the endpoint descriptions alone.

Counts from relatively small treatment groups are inherently limited for evaluating uncommon events. A zero count is compatible with uncertainty about events that might occur in a larger or different population. Similarly, differences in the numbers of participants with other adverse events are descriptive and cannot be treated as causal comparisons without the relevant analysis. The registry record does not report uncertainty intervals or statistical tests for these summaries.

The study’s Phase 1 setting and short treatment schedules are also important context. The posted treatment regimens lasted 4 weeks, while the primary safety observation period extended through final follow-up at Day 57. The study summary describes participation lasting up to approximately 16 weeks. These features define the scope of observation; they do not support conclusions about longer-term outcomes.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how early clinical studies can organize safety, pharmacokinetic, and pharmacodynamic questions across several treatment schedules. Randomization and double masking are design features intended to support more credible group comparisons, while the parallel-group structure assigns participants to distinct regimens. The inclusion of placebo and dulaglutide groups gives the study comparators within its design.

At the same time, the record illustrates why counts need their context. The groups have different numbers at risk, and the LY3493269 regimens include both fixed and escalating doses. A raw count does not adjust for group size, establish a causal contrast, or show whether an event was considered related. The primary endpoint’s investigator-related definition is also not interchangeable with adverse-event summaries regardless of causality.

For clinical researchers, the distinction between an endpoint definition and its reported result is central. The record describes what the primary safety endpoint was intended to count and when it was assessed, but the registry entries available for this analysis do not include its group-specific related-event counts or a formal analysis. That gap prevents a direct comparison on the primary question, even though broader adverse-event counts are reported.

More generally, this study demonstrates the value of transparent reporting of analysis populations, event attribution, uncertainty, missing data, and planned comparisons. These details determine whether readers can move from descriptive observations to a statistical comparison. Where they are not reported in the registry record, interpretation should remain limited to the observed summaries and design features rather than filling in an assumed analysis.

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 registry record provides limited detail for interpreting the primary endpoint result. It defines the endpoint and its population but the registry entries available for this analysis do not include group-specific counts of events considered related to study drug. The posted serious- and other-event summaries therefore cannot answer the primary endpoint question directly.

The record does not report confidence intervals, hypothesis tests, adjusted estimates, or a statistical model for the safety summaries. It also does not report allocation ratios, detailed randomization or masking procedures, missing-data handling, or an account of participants excluded from particular outcome analyses. The absence of those details limits assessment of precision and potential sources of bias.

The study included multiple treatment regimens, including escalating doses, and the adverse-event groups differ in their numbers at risk. Simple comparisons of counts cannot separate regimen effects from group-size differences or random variation. The registry record does not report a dose-response analysis or a prespecified pairwise comparison. It also does not report how multiplicity across treatment groups and secondary outcomes was handled.

The primary safety endpoint covers through Day 57, while each treatment schedule is described as lasting 4 weeks. The study summary says participation could last up to approximately 16 weeks, but the registry entries do not specify outcome completeness or follow-up by group. Results for pharmacokinetic and pharmacodynamic measures are not included in the registry record for this analysis. These limits restrict conclusions to the recorded design and adverse-event counts, rather than broader claims about efficacy, longer-term safety, or comparative treatment effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of LY3493269 in Participants With Type 2 Diabetes — NCT04515576.
• Registry record last updated 2025-01-14; status last verified 2024-12.
• Results first posted 2025-01-14.
• 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

NCT04515576 is a completed, randomized, double-masked, parallel-group Phase 1 study sponsored by Eli Lilly and Company. It enrolled participants with type 2 diabetes and evaluated LY3493269 alongside placebo and dulaglutide. Treatment groups included fixed and escalating LY3493269 schedules; the active and placebo regimens were given subcutaneously once weekly for 4 weeks.

The primary endpoint counted participants with one or more treatment-emergent or serious adverse events considered related to study drug administration, from baseline through final follow-up at Day 57. Posted adverse-event summaries report zero serious events and zero deaths in every group, alongside group-specific counts for other adverse events. Those broader counts are not equivalent to the investigator-related primary endpoint. The registry record lists pharmacokinetic and fasting plasma glucose outcomes, but their numerical results are not reported in the registry record for this analysis.