This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of LY2599506 (Oral Agent Medication: Glucokinase Activator 1) in Type 2 Diabetes Mellitus (NCT01029795), a randomized phase 2 study. The primary outcome is Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 12 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01029795 |
| Phase | Phase 2 |
| Condition | Diabetes Mellitus, Type 2 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 38 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Participants with type 2 diabetes mellitus. The registry record states that the study enrolled 38 participants and that the primary outcome data were reviewed but not presented because of insufficient sample size.
Intervention
LY2599506, an oral glucokinase activator, administered in escalating doses based on predefined glycemic targets. The arm description lists doses from 100 mg/day up to 800 mg/day using active and matching placebo capsules.
Comparator
Glyburide, also administered in escalating doses based on predefined glycemic targets. The registry lists doses from 5 mg/day up to 20 mg/day using active and matching placebo capsules. Placebo is also listed as an intervention.
Primary question
The stated primary outcome was change in HbA1c from baseline at 12 weeks. The study’s brief summary asks whether taking LY2599506 for 12 weeks controls blood sugar better than taking glyburide for 12 weeks. The registry does not present the HbA1c results needed to assess that comparison.
The official title describes a 12-week, phase 2, randomized, double-blind, active-controlled study of LY2599506 as monotherapy or in combination with metformin. The listed primary outcome concerns change in glycosylated hemoglobin A1c, a measure of average blood glucose over time. Other stated aims included evaluating safety, assessing blood-sugar control, determining dose, and examining weight effects. Those aims do not substitute for a reported primary-outcome estimate.
The registry record identifies glyburide as the active comparator and lists placebo among the interventions. The arm descriptions specify active capsules alongside matching placebo capsules; further details about how participants were assigned to particular treatment combinations are not reported in the registry record. As the primary outcome is not presented, the central comparative question remains unanswered by the posted results.
3. Trial Design
This was a phase 2 randomized, double-blind, parallel-group study with an active control. It enrolled 38 participants and is listed as terminated. The study’s official title describes a 12-week treatment comparison, while its brief summary describes screening, a 4-week dose adjustment period, an 8-week treatment period, and a 4-week follow-up period. The primary outcome was specified at 12 weeks; several secondary outcomes were specified at 12 weeks and 16 weeks.
The intervention descriptions state that LY2599506 and glyburide doses were escalated according to predefined glycemic targets. LY2599506 was described as escalating from 100 mg/day up to 800 mg/day, and glyburide from 5 mg/day up to 20 mg/day. Capsules of active drug were paired with matching placebo capsules. The registry lists placebo as an intervention, but the available arm descriptions do not provide a full account of allocation across treatment combinations.
Randomization means that treatment assignment is intended to be determined by chance, helping limit systematic differences between groups. Double blinding means that treatment assignments are masked, although which study roles were blinded is not reported in the registry record. A parallel-group design assigns participants to treatment groups that proceed alongside one another rather than crossing over between treatments.
The registry record does not report the reason the trial was terminated, the planned or achieved allocation ratio, or the number of participants in each arm beyond the safety denominators. Further details about the randomization sequence and concealment are not reported in the registry record. The primary outcome description says the study ended after enrolling 38 participants and that the outcome data were reviewed but not presented because the sample was considered too small for appropriate numerical summaries and statistical comparisons.
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
| Stage | LY2599506 | Glyburide |
|---|---|---|
| STARTED | 16 | 22 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 16 | 22 |
Reasons for not completing this period:
| Reason | LY2599506 | Glyburide |
|---|---|---|
| Entry Criteria Not Met | 2 | 1 |
| Physician Decision | 2 | 1 |
| Sponsor Decision | 11 | 17 |
| Withdrawal by Subject | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: Data were reviewed but are not presented due to insufficient sample size.
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.
| Characteristic | Unit | LY2599506 | Glyburide | Total |
|---|---|---|---|---|
| Participants analysed | 16 | 22 | 38 | |
| Age Continuous | years | 59.76 (SD 6.74) | 59.38 (SD 5.86) | 59.54 (SD 6.16) |
| Sex: Female, Male: Female | Participants | 6 | 7 | 13 |
| Sex: Female, Male: Male | Participants | 10 | 15 | 25 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 16 | 21 | 37 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Australia | participants | 5 | 9 | 14 |
| Region of Enrollment: Austria | participants | 2 | 3 | 5 |
| Region of Enrollment: Czech Republic | participants | 1 | 2 | 3 |
| Region of Enrollment: Israel | participants | 2 | 1 | 3 |
| Region of Enrollment: Russian Federation | participants | 2 | 2 | 4 |
| Region of Enrollment: Spain | participants | 4 | 5 | 9 |
| Duration of Diabetes in Years | year | 6.08 (SD 5.03) | 7.73 (SD 5.64) | 7.03 (SD 5.38) |
| Percentage of Glycosylated Fraction of Hemoglobin A1c | percentage of glycosylated hemoglobin | 7.90 (SD 0.75) | 7.78 (SD 1.02) | 7.83 (SD 0.91) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 12 Weeks, measured over Baseline, 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of glycosylated hemoglobin |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in glycosylated hemoglobin A1c (HbA1c) at 12 weeks. The registry defines change as HbA1c at week 12 minus HbA1c at baseline, and gives the unit as percentage of glycosylated hemoglobin. The planned summary measure was the mean, with standard deviation as the stated measure of dispersion.
HbA1c is used in diabetes studies as a measure of blood-glucose control over time. In general, a change-from-baseline endpoint compares each participant’s follow-up measurement with that participant’s starting measurement. Comparing average changes between randomized groups can describe whether the groups’ measured responses differed over the study period. The change-score definition also makes the direction explicit: the follow-up value is subtracted by the baseline value.
The registry record does not provide baseline or follow-up HbA1c summaries, a mean change, a between-group estimate, a confidence interval, or a statistical test for this endpoint. It states that the data were reviewed but not presented because of insufficient sample size and that numerical summaries and statistical comparisons were considered potentially misleading. Therefore, the endpoint’s intended measurement is known, but its numerical result cannot be interpreted from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the primary HbA1c outcome is not presented. The registry gives the endpoint definition and analysis time point, but no numerical change from baseline and no comparison between LY2599506 and glyburide. It explicitly states that the study was terminated after enrolling 38 participants and that the sample size was too small for appropriate numerical summaries or statistical comparisons. No estimate of the primary treatment contrast, confidence interval, or p-value is reported in the registry record.
That absence prevents a conclusion about the size, direction, or precision of the HbA1c difference between the groups. It also prevents assessment of whether any estimated difference might be compatible with a range of values. A confidence interval, in general, expresses uncertainty around an estimate; without a reported estimate and interval, the degree of statistical precision cannot be evaluated. The registry’s reason for withholding the outcome is itself important context: the lack of a result is not evidence that the treatments had identical outcomes.
The study record does contain safety counts, but those counts answer a different question from the primary efficacy endpoint. They describe participants with serious or other adverse events in the safety groups. They do not supply the missing HbA1c comparison, and their small group counts warrant a descriptive reading rather than a claim of comparative safety. Event counts alone also do not establish that a treatment caused an event.
The record lists 24 outcome measures and no analyses. It lists secondary measures including ECG QT interval, HOMA2 beta-cell function and insulin sensitivity, blood lipids and free fatty acids, quality of life, treatment satisfaction, low-blood-sugar experience, and diabetes symptoms. The fact that these outcomes are listed does not mean that results for them were reported or that statistical tests were performed. Further outcome estimates are not reported in the registry record.
There is consequently no basis in the posted results for quantifying a treatment effect, claiming superiority or equivalence, or judging the clinical importance of a difference. A failure to report a comparison is not a statistically nonsignificant result: no reported test statistic or p-value establishes that. Nor can the trial’s completion status or enrollment count alone establish what would have been observed with a larger study. The defensible interpretation is limited to the study design, stated outcome, and registry explanation for withholding numerical results.
General statistical context: small samples tend to produce less precise estimates, and estimates can be sensitive to the values observed among a small number of participants. That is one reason to interpret unstable or incomplete summaries cautiously. In this record, the sponsor’s stated decision was not to present the primary outcome data at all; therefore there is no posted effect estimate to qualify or reinterpret.
9. Statistical Methods Explained
The primary outcome was defined as a continuous change score: HbA1c at week 12 minus HbA1c at baseline. The registry specified the mean as the summary parameter and standard deviation as the dispersion measure. The mean describes the average change in a group. The standard deviation describes how spread out individual measurements are around that group average; it is not the uncertainty interval for the mean.
General statistical explanation: a treatment comparison for a continuous endpoint can be expressed as the difference between the groups’ average changes. That contrast would indicate the direction and size of the observed difference in the endpoint’s units. An uncertainty interval around the contrast would show how precisely the data estimate it. The registry record does not report the mean changes, a contrast, or an uncertainty interval for HbA1c, so none can be interpreted for this trial.
Randomization is a design method intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. It does not guarantee that groups are identical, especially in a small study. Blinding can reduce the influence of treatment expectations on care, reporting, or assessment, depending on who is blinded and how outcomes are collected. Although the record identifies the study as randomized and double-blind, additional operational details are not reported in the registry record.
The registry describes dose adjustment according to predefined glycemic targets. In general, a target-based adjustment approach changes the administered dose in response to whether measured outcomes meet specified targets. The description gives dose ranges for LY2599506 and glyburide, but does not report the detailed adjustment algorithm, timing of dose decisions, or how deviations from the planned approach were handled. Those details are not reported in the registry record and should not be inferred from the dose ranges alone.
General statistical explanation: an analysis of change from baseline can be reported as the average within-group change, as a comparison of changes between groups, or with a model that accounts for baseline values. These approaches answer related but not identical questions and rely on particular assumptions. The exact statistical model used for the primary endpoint is not reported in the registry record. The endpoint description’s reference to a mean and standard deviation identifies a planned descriptive summary, but does not by itself specify the inferential model.
A p-value, when reported, is a measure tied to a statistical test and its null hypothesis; it is not the probability that a treatment works or that the null hypothesis is true. A confidence interval describes uncertainty around an estimate under the method’s assumptions. Neither a p-value nor a confidence interval is reported for the primary comparison. Because the outcome itself is not presented, there is no sponsor-reported test or interval to interpret.
General statistical explanation: over-dispersion occurs when the variation in observed data exceeds what a chosen statistical model assumes. It can make standard errors and tests unreliable if the model does not account for the extra variability. The primary HbA1c outcome is continuous, and the registry does not report an over-dispersion assessment or a model for it. There is therefore no reason to assert that over-dispersion affected this analysis.
The registry lists 24 outcome measures and no analyses. It specifies the primary endpoint and lists secondary outcomes, but does not report an analysis plan explaining which outcomes were tested, in what order, or with what adjustments for multiple comparisons. The specific tests and models for the secondary measures are not reported in the registry record. No interim analyses or stopping boundaries are reported in the registry record, and no explanation of the termination decision is given.
General statistical explanation: testing many outcomes can increase the chance that at least one result appears notable by chance. Multiplicity procedures can address that issue, but the appropriate approach depends on the questions and analysis plan. The presence of numerous listed outcomes does not demonstrate that each was tested or that any particular correction was applied. Here, the analysis methods and multiplicity handling are not reported in the registry record.
Any sample-size illustration should be read as planning context, not as observed power or as a feature of the trial’s own design. In general, a planning calculation asks how many participants might be needed to detect a specified effect under stated assumptions. It does not show the probability that the completed trial detected an effect, and it cannot replace a reported estimate and its uncertainty. The registry does not report the trial’s sample-size justification or a prespecified effect size. It also does not report a primary endpoint estimate from which a trial-specific planning illustration could be interpreted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 24 outcome measures, including the primary HbA1c change and multiple secondary outcomes. These secondary measures cover ECG QT interval, HOMA2 measures of beta-cell function and insulin sensitivity, blood lipids and free fatty acids, quality of life, treatment satisfaction, low-blood-sugar experience, and diabetes symptoms. The registry record does not report a statistical plan for controlling the risk of chance findings across multiple outcomes or time points.
General statistical explanation: when several outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result by chance can increase. A prespecified testing hierarchy or adjustment method can help define how such results should be interpreted. No hierarchy, adjustment procedure, or detailed testing plan is reported in the registry record. The record’s list of outcomes alone does not show that all were analyzed.
The primary outcome description says the data were reviewed but not presented because of insufficient sample size. The record lists no analyses, and numerical primary results are absent. The exact statistical analysis populations, rules for inclusion, and handling of missing endpoint measurements are not reported in the registry record. The amount and pattern of missing data are also not reported.
General statistical explanation: missing-data methods can affect estimates when some participants do not have the measurements needed for an analysis. Appropriate interpretation depends on how much data are missing, why they are missing, and what assumptions the analysis makes. Since these details are not reported, it is not possible to evaluate how missing observations may have affected the endpoint. The record’s statement that data were reviewed does not identify the analysis population or establish that every participant had a complete measurement.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| LY2599506 | 1 | 16 | 6.2% |
| Glyburide | 0 | 22 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 4% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| LY2599506 | 5 of 16 |
| Glyburide | 5 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | LY2599506 | Glyburide |
|---|---|---|---|
| Hepatitis | Hepatobiliary disorders | 1 of 16 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | LY2599506 | Glyburide |
|---|---|---|---|
| Headache | Nervous system disorders | 2 of 16 | 0 of 22 |
| Vision blurred | Eye disorders | 0 of 16 | 1 of 22 |
| Abdominal discomfort | Gastrointestinal disorders | 1 of 16 | 0 of 22 |
| Constipation | Gastrointestinal disorders | 1 of 16 | 0 of 22 |
| Nausea | Gastrointestinal disorders | 0 of 16 | 1 of 22 |
| Asthenia | General disorders | 0 of 16 | 1 of 22 |
| Fatigue | General disorders | 0 of 16 | 1 of 22 |
| Infectious mononucleosis | Infections and infestations | 1 of 16 | 0 of 22 |
| Influenza | Infections and infestations | 0 of 16 | 1 of 22 |
| Lower respiratory tract infection | Infections and infestations | 0 of 16 | 1 of 22 |
Serious events with the highest arm-level rate: hepatitis (6.2%).
The registry lists serious adverse events for 16 participants at risk in the LY2599506 group, with 1 participant affected. In the glyburide group, 22 participants were at risk, with 0 participants affected. For other adverse events, the registry lists 16 at risk and 5 affected in the LY2599506 group, and 22 at risk and 5 affected in the glyburide group. These are descriptive counts, not estimates of comparative risk.
The serious-event term listed as a top term is hepatitis, at 6.2%. The registry information does not identify an arm for that term in the listed summary, so it should not be assigned to a treatment group. Death counts are not reported in the registry record.
General statistical explanation: adverse-event counts depend on the group size, the event definition, the observation period, and how events are collected. Small counts are imprecise, and a count in one group versus another does not by itself establish a treatment-related difference. The record does not provide detailed event descriptions, exposure-adjusted rates, or a statistical comparison of safety outcomes. These figures should therefore be read as the posted counts, not as proof that an intervention caused or prevented an event.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, double-blind phase 2 study intended to compare LY2599506 with glyburide in participants with type 2 diabetes. It also documents that the trial was terminated after enrolling 38 participants. The primary endpoint was clearly defined as change in HbA1c from baseline at 12 weeks, but its numerical results were not presented because the registry description says the sample was insufficient for appropriate numerical summaries and statistical comparisons.
For that reason, the posted results do not show whether the average HbA1c change favored either group, how large a difference there may have been, or how uncertain such a difference was. They do not establish equivalence, lack of effect, or superiority. The absence of a reported estimate is not the same as a result showing no difference. The stated reason for not presenting the endpoint should be kept distinct from an inferential finding.
The safety counts provide limited descriptive information about participants with reported serious and other adverse events. They cannot answer the primary efficacy question, and they do not by themselves establish causality or a reliable difference between treatments. The registry’s list of secondary outcomes likewise indicates what was intended for assessment, not what the trial demonstrated.
General statistical context: a small study can leave substantial uncertainty, but the amount of uncertainty can only be assessed from reported estimates and their precision. Since the primary outcome results are withheld, no quantitative treatment-effect conclusion can be drawn from this record. The study’s termination and enrollment count do not reveal what the omitted measurements would have shown, nor do they indicate why the study stopped; the reason for termination is not reported in the registry record.
The appropriate reading is therefore narrow: the registry records the planned comparison and endpoint, the enrollment and termination status, and limited safety counts, but it does not provide the primary outcome result needed to answer the main comparative question. No medical conclusion about treatment benefit or lack of benefit follows from the absence of that result.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a planned endpoint and a reported result. The registry specifies HbA1c change at 12 weeks as the primary outcome, including the direction of subtraction and the planned descriptive statistics. Yet the outcome is not presented. Knowing the endpoint definition does not reveal what the participants’ measurements were or what treatment contrast was observed.
That distinction matters because readers may otherwise treat a missing result as if it were a null finding. A trial that reports no difference after analysis is different from a trial whose primary outcome is not numerically reported. The registry explicitly attributes the omission to the small sample and warns that summaries and comparisons may be misleading. That statement frames the available evidence; it does not supply an unreported estimate.
The record also demonstrates why design features and sample size should be considered separately from results. Randomization and double blinding describe intended safeguards in the study design. They cannot compensate for the absence of the primary outcome estimate, and they do not make unreported analyses available. Likewise, the enrollment count alone does not indicate the direction or size of an effect.
General statistical context: precision is central to interpretation. Estimates based on limited information may be unstable, and an uncertainty interval helps show the range of values compatible with the data under a specified method. Without an estimate or interval, readers cannot judge precision directly. A planning calculation is also not a substitute for observed results and should not be interpreted as observed power.
For clinical researchers and biostatisticians, the key lesson is to distinguish registry design information, descriptive safety counts, and analyzed endpoint results. In this record, the first two are available to a limited extent, while the primary efficacy result and detailed analysis methods are not reported. This boundary prevents unsupported conclusions while preserving what the registry does document.
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 main limitation for interpreting this trial is that the primary HbA1c outcome is not presented. Although the registry states that data were reviewed, it provides no numerical summaries or statistical comparisons because of insufficient sample size. As a result, the treatment effect and its precision cannot be assessed from the posted results.
The record lists 38 participants overall, but does not provide the number analyzed for the primary endpoint or the analysis population definition. The safety groups list 16 and 22 participants at risk, but those denominators do not supply missing efficacy results. The reason for trial termination is not reported in the registry record.
Details needed to evaluate the analysis are also absent, including the statistical model, handling of missing measurements, and methods for multiple outcomes and time points. The record does not report the randomization procedure, allocation concealment, exact masking roles, or detailed dose-adjustment rules. These limitations concern what can be established from the registry record; they do not show that any particular method was or was not used.
The study description identifies a 12-week treatment comparison and follow-up assessments, but the primary endpoint has no posted estimate. Secondary outcomes are listed without reported results. Safety information is limited to event counts and a serious-event term, without a reported treatment comparison or detailed causal assessment. These gaps restrict both efficacy interpretation and broader assessment of the trial’s results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of LY2599506 (Oral Agent Medication: Glucokinase Activator 1) in Type 2 Diabetes Mellitus — NCT01029795.
- Registry record last updated 2011-12-02; status last verified 2011-11.
- Results first posted 2011-10-26.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT01029795, a phase 2, randomized, double-blind, parallel-group study of LY2599506 and glyburide in participants with type 2 diabetes mellitus. The official title describes a 12-week active-controlled study, and the brief summary lists screening, dose adjustment, treatment, and follow-up periods. The study enrolled 38 participants and is listed as terminated.
The primary outcome was change from baseline in HbA1c at 12 weeks. The record says the data were reviewed but are not presented because of insufficient sample size. It lists 24 outcome measures and no analyses. Safety counts are reported for serious and other adverse events, but they do not replace the missing primary comparison. The reason for termination, detailed analysis methods, and missing-data procedures are not reported in the registry record.