A Study of LY3025876 in Participants With Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3025876 in Participants With Diabetes (NCT01870297), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration.

2. Clinical Question

The study’s stated main purpose was to assess the safety and tolerability of LY3025876 given alone in Part A and in combination with liraglutide in Part B. The primary endpoint is specifically about serious adverse events judged by the investigator to be related to study drug administration. It is not a count of every adverse event, nor does it capture all measures of safety or tolerability.

The registry record also lists pharmacokinetic outcomes for LY3025876, immunogenicity, and change from baseline to Day 28 in fasting glucose as secondary outcomes. The posted primary endpoint results do not answer those other questions. Their results are not reported in the registry record details available for this analysis.

3. Trial Design

This was a randomized, double-blind, parallel phase 1 study sponsored by Eli Lilly and Company. The registry record describes 72 participants with type 2 diabetes mellitus and lists the study as completed. The recorded start was 2013-06, and primary completion was 2014-12.

The study had two parts. Part A compared placebo with four LY3025876 dose groups: 0.5 mg, 1.5 mg, 5 mg, and 15 mg, administered once daily by subcutaneous injection for up to 28 days. Part B examined LY3025876 in combination with liraglutide. The active combination was 5.0 mg LY3025876 and 1.8 mg liraglutide, administered as separate once-daily injections for up to 28 days after liraglutide titration over 2 weeks. Part B also included placebo matching LY3025876, with and without liraglutide.

Randomization is intended to reduce systematic differences between groups at assignment. Double masking means the study was described as double-blind, although which parties were masked is not reported in the registry record. A parallel design assigns participants to a study group rather than describing a crossover between treatments. Details of the randomization procedure, allocation concealment, and masking procedures are not reported in the registry record.

The primary endpoint population is described as all randomized participants who received at least one dose of study drug. This is not necessarily identical to every randomized participant, because the stated definition excludes those who did not receive a dose. The registry record does not report how many randomized participants, if any, were excluded by that definition or how missing outcome information was handled.

The stated timeframe for the primary endpoint was predose on Day 1 up to Day 56 in each part. That interval defines when events were counted; the listed treatment courses themselves were up to 28 days. The registry record does not report a sample-size justification or further details of the study’s operational design.

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: Dose escalation was planned for 20 milligrams (mg) of LY3025876 but dose escalation was only up to 15 mg LY3025876.

Only the first 6 of 7 groups are shown.

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 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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration, measured over Predose on Day 1 up to Day 56 in each Part.

The primary endpoint counts participants with one or more serious adverse events that the investigator considered related to study drug administration. It is a participant count, not a count of every event experienced by those participants. A participant with multiple qualifying events would still be counted as a participant with at least one event under this endpoint definition.

Serious adverse events are important to monitor in a phase 1 study focused on safety and tolerability. Requiring the investigator to assess relatedness narrows this endpoint to events judged connected to study drug administration. That judgment is distinct from whether an event was serious: an event may be serious without being considered related. The registry record directs readers to a separate reported-adverse-events section for summaries of other non-serious adverse events and all serious adverse events, regardless of causality.

The specified observation period runs from predose on Day 1 up to Day 56 in each part. The endpoint does not by itself describe the type, timing, duration, or severity of non-serious events, nor does it summarize laboratory, pharmacokinetic, immunogenicity, or fasting-glucose outcomes. Results for those measures should not be inferred from the primary count.

For this endpoint, the posted results show zero participants in each listed arm with a serious adverse event considered related to study drug administration. That observation describes the reported counts during the defined period; it does not establish that the underlying risk is zero.

7. Results Posted in the Registry

• 0.5 mg LY3025876: 0.0% (0/15) versus 0.0% (0/11) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• 15 mg LY3025876: 0.0% (0/10) versus 0.0% (0/11) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• 5.0 mg LY3025876 + Liraglutide: 0.0% (0/10) versus 0.0% (0/11) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary outcome is binary at the participant level: a participant either had one or more qualifying events during the specified period or did not. The reported statistic is a count of participants with an event. This differs from an event count, which could include multiple events for the same person, and from a rate that accounts for person-time.

What does a risk difference mean? In general, a risk difference subtracts the proportion with an event in one group from the proportion in another. A value of 0.0 indicates that the observed proportions are the same in the comparison as calculated. In the posted comparisons, both groups have zero qualifying events, so each reported risk difference is 0.0. This descriptive equality in the observed data does not establish equality of the underlying risks.

Why does an all-zero outcome need careful interpretation? When no events are observed, ordinary calculations based on observed proportions can give an incomplete picture of uncertainty. The data establish that no qualifying event was recorded among the participants included in these results. They cannot rule out events in a larger population or outside the observed timeframe. In general, uncertainty about a rare event is particularly sensitive to the amount of observation and the event definition. The registry record does not report a model or procedure for estimating event risks when all groups have zero events.

What do the comparative values convey? The registry record includes risk-difference comparisons against Placebo Part A for 0.5 mg LY3025876, 15 mg LY3025876, and 5.0 mg LY3025876 + Liraglutide. Each reported estimate and both bounds are 0.0. These comparisons concern only the stated contrasts, not every arm-to-arm comparison. The comparison values are consistent with the displayed counts, but the registry record does not identify a confidence level, a hypothesis-testing method, or a prespecified inferential procedure for them. The record lists no analyses.

What does randomization contribute? In general, randomization aims to make assigned groups comparable with respect to measured and unmeasured factors at the start of a trial. Its benefits depend on implementation and on how participants are handled after assignment. The registry record identifies the allocation as randomized but does not report the sequence-generation method, concealment details, or whether the reported endpoint analysis followed a prespecified intention-to-treat approach. The endpoint population is instead described as randomized participants who received at least one dose.

How should masking be understood? The study is described as double-blind. In general, masking can reduce the influence of expectations on participant reporting, clinical care, and outcome assessment. The record does not state which groups of people were masked, how masking was maintained, or whether it was ever broken. Investigator judgment of relatedness may involve clinical assessment, but the exact assessment process is not reported.

What is not available about the statistical plan? The registry record does not report a sample-size justification, a formal statistical analysis plan, an interim-analysis plan, or a multiplicity procedure. It also does not report methods for missing data, adjustment for baseline characteristics, or methods for handling protocol deviations. The absence of these details in the registry record does not show that no such procedures existed; it means they are not reported in the registry record.

How does the sample-size illustration differ from observed evidence? The posted sample-size material is described as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations concern planning for a future study under stated assumptions; they are not observed power and do not alter the current trial’s observed event counts. The record’s general description says that planning rows use a stated fraction of the observed effect. No numerical planning results are reported in the registry record details available for this explanation, so no sample-size values can be interpreted.

Why does the endpoint definition matter? The outcome combines an event’s seriousness with an investigator’s judgment about relatedness. In general, definitions shape what is counted and can affect how results compare across studies. Here, events considered unrelated are not part of the primary endpoint, even though the registry record separately describes reporting all serious events regardless of causality. The primary result should therefore be read as a count under this specific definition, rather than as a complete accounting of all safety events.

10. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an underlying quantity, not merely whether the observed estimate is numerically small. In general, a confidence interval expresses a range of values compatible with the data under a specified statistical method and confidence level. Its width depends on the amount of information and on the method used.

For the primary endpoint, every listed group has zero observed participants with a related serious adverse event. The three posted risk-difference comparisons also report estimates and lower and upper values of 0.0. Although these displayed bounds have no numerical width, the registry record does not report their confidence level or the procedure used to construct them. They should not be interpreted as showing that the underlying risk difference is known exactly.

All-zero event data pose a particular interpretive challenge. The observed proportion is zero, but a finite group with no observed events can still be compatible with a nonzero underlying event risk. General statistical methods can represent uncertainty differently when events are absent; the registry record does not identify which method, if any, was used for uncertainty estimation in the posted comparisons. A reported point estimate alone does not convey the full range of plausible values.

The observation window also matters for precision and interpretation. The endpoint covers predose on Day 1 up to Day 56 in each part. The results therefore describe events recorded over that period, not events after it. The record does not report additional follow-up for this endpoint or precision estimates for other safety outcomes.

The arm sizes are limited, and the primary results contain no qualifying events. Accordingly, the result is informative about what was observed in these study groups but provides limited resolution about the frequency of uncommon serious events in a broader population. The absence of reported precision methods and confidence levels further limits formal interpretation of the comparative bounds.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and four secondary outcome descriptions: LY3025876 area under the concentration-time curve from time 0 to 24 hours, maximum concentration, anti-LY3025876 antibodies, and change from baseline to Day 28 in fasting glucose. It does not report results for those secondary outcomes in the information used for this analysis.

When several outcomes or comparisons are examined, general statistical practice may consider multiplicity: the chance of at least one apparently notable finding can increase as the number of tests grows. Methods such as prespecifying a primary comparison or adjusting for multiple testing can address that issue, but the registry record does not report a multiplicity plan. It also does not state whether all listed outcomes were analyzed or how any tests would be interpreted together. No multiplicity-adjusted results are reported in the registry record.

The posted primary comparisons cover three contrasts with Placebo Part A. The record does not state whether those contrasts were prespecified, whether additional comparisons were conducted, or whether the displayed values were intended as confirmatory inference. The absence of an analysis count in the record should not be taken as evidence that analyses were not performed; the analyses are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary population is defined as randomized participants who received at least one dose, but the record does not describe how missing endpoint information, withdrawal, or incomplete follow-up was handled. It does not report whether outcomes were assumed absent when not recorded, whether participants with incomplete observation were excluded, or whether sensitivity analyses were conducted.

These omissions matter because the interpretation depends on which participants contribute to the endpoint and on how incomplete observations are treated. The displayed zero counts describe the reported analysis population. They cannot establish that every randomized participant had complete observation through the full timeframe. The record does not report a statistical analysis plan, an interim-analysis plan, or a sample-size justification.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 primary safety result counts participants with one or more serious adverse events that the investigator considered related to study drug administration. The count is 0.0 in each of the seven listed arms. The arm denominators reported for this endpoint range across the listed groups; the results should be read arm by arm rather than as a combined total.

Zero observed related serious adverse events is not the same as evidence that no serious adverse events occurred. The primary endpoint excludes serious events judged unrelated to study drug administration. The registry record states that summaries of all serious adverse events regardless of causality, as well as other non-serious adverse events, are located in the reported-adverse-events section.

Separate adverse-event summaries also report zero related serious events in their listed groups and provide counts for participants with other adverse events. Those summaries are separate from the primary endpoint, and the group listings are not identical in every label or denominator. The primary endpoint should not be combined with those other-event counts or interpreted as an overall adverse-event total.

Relatedness is an investigator judgment, and the registry record does not describe the assessment process. The figures therefore summarize recorded events under the study’s stated endpoint definition and observation period, rather than all possible safety outcomes or risks beyond follow-up.

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

The result establishes that the posted primary endpoint recorded no participants with a serious adverse event judged related to study drug administration in any listed arm during the specified timeframe. It also shows no observed difference in this endpoint among the three comparisons reported against Placebo Part A, because each displayed risk difference is 0.0.

That is a description of the observed study data, not a conclusion that the underlying risks are identical. The absence of events in a finite study cannot rule out uncommon events, and the displayed comparative bounds do not settle that uncertainty when their confidence level and method are not reported. The result also does not show that no serious adverse events occurred for other reasons, since the primary endpoint is restricted to investigator-assessed related events.

The study was designed to assess safety and tolerability, pharmacokinetics, and pharmacodynamics across LY3025876 dosing and combination conditions. The primary result alone does not establish conclusions about all aspects of safety, tolerability, drug exposure, immune response, or fasting glucose. Although these secondary outcomes are listed in the registry record, their results are not reported in the information available for this analysis.

Nor does the posted primary endpoint establish comparative effectiveness or support conclusions about clinical use. The record describes a phase 1 study with treatment courses of up to 28 days and a primary safety observation period through Day 56 in each part. It does not provide evidence about outcomes beyond that recorded period.

The most defensible reading is therefore specific: no related serious adverse events were reported for the primary endpoint in the listed groups over the stated observation window. The result is reassuring only as a description of those observations; it is not proof of zero risk, a demonstration of equivalence, or a substitute for the broader adverse-event summaries.

14. Why This Trial Matters Statistically

This trial illustrates why safety endpoints require precise definitions. “Serious adverse events considered related” is narrower than “all serious adverse events” and differs from a count of any adverse event. The distinction between event seriousness and an investigator’s assessment of relatedness shapes what the primary count can say.

The posted results also illustrate a common challenge in early studies: when an outcome has no observed events, groups may look identical on the observed scale while uncertainty about underlying event risks remains. A risk difference of 0.0 in these data is a statement about the recorded proportions, not proof that treatment groups have identical risks. Interpreting all-zero results requires attention to group size, observation time, and the method used to express uncertainty.

The trial’s two-part structure provides different treatment contexts: LY3025876 alone in Part A and LY3025876 with liraglutide in Part B. That design makes it important to interpret each arm in its stated context rather than treat every group as a single interchangeable comparison. The registry record reports only selected risk-difference comparisons against Placebo Part A, so those results do not summarize every possible contrast.

Finally, the registry record demonstrates the value of distinguishing outcome listings from outcome results. It identifies pharmacokinetic, immunogenicity, and fasting-glucose outcomes, but their results are not reported in the record information. The primary safety count cannot stand in for those measures. Clear conclusions depend on matching each statistical statement to the endpoint, population, comparison, and timeframe it actually represents.

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 main limitation for interpreting this trial’s primary result is the absence of observed qualifying events. With zero events in every listed arm, the data do not quantify a difference in observed event frequency, but they also cannot establish that underlying risks are zero or equivalent. The registry record does not report a confidence level or method for the comparative bounds.

The endpoint relies on investigator judgment that a serious adverse event was related to study drug administration. The registry record does not describe how relatedness was assessed, whether the assessment was blinded, or how disagreements were handled. The record does not report the event-level detail needed to characterize timing, clinical type, or severity for the primary endpoint.

The primary population includes randomized participants who received at least one dose. The record does not report how many randomized participants did not receive a dose, whether any participants had incomplete follow-up, or how missing outcome data were handled. The relationship between the primary endpoint population and all randomized participants therefore cannot be fully assessed from the record.

Other limitations include the lack of a reported statistical analysis plan, sample-size justification, interim-analysis details, and multiplicity procedure. The registry record lists secondary outcomes but does not report their results in the information. The primary endpoint covers only the specified observation window, and the record does not report further follow-up for this endpoint.

Finally, the study is described as phase 1 and includes separate monotherapy and combination-treatment arms. Its findings are specific to the reported groups and period. The posted primary result should not be generalized to unreported outcomes, longer-term safety, or populations and treatment settings not described in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY3025876 in Participants With Diabetes — NCT01870297.
• Registry record last updated 2019-01-24; status last verified 2018-08.
• Results first posted 2019-01-24.
• 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

NCT01870297 is a completed randomized, double-blind, parallel phase 1 study of LY3025876 in participants with type 2 diabetes mellitus. The registry record lists enrollment of 72, a start date of 2013-06, and primary completion in 2014-12. The study examined LY3025876 alone in Part A and with liraglutide in Part B.

The primary endpoint was the number of participants with one or more serious adverse events considered related to study drug administration, from predose on Day 1 up to Day 56 in each part. The posted count is zero in every listed arm. Three reported risk-difference comparisons against Placebo Part A also have estimates and bounds of 0.0.

These findings describe the recorded primary endpoint, not all serious or non-serious adverse events and not all listed secondary outcomes. The registry record does not report the statistical analysis plan, missing-data methods, multiplicity procedure, confidence level for the comparison bounds, or results for the listed secondary outcomes.