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 Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253) (NCT01614769), a randomized phase 1 study. The primary outcome is Recovery Time From Hypoglycemia to Euglycemia.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01614769 |
| Phase | Phase 1 |
| Condition | Type 2 Diabetes Mellitus |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 10 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with type 2 diabetes mellitus took part in this Phase 1 study. The registry record lists enrollment of 10. The primary outcome analysis used a per-protocol population: participants who received study drug and completed the necessary post-treatment measurements for at least one treatment period.
Intervention
The active treatments were glimepiride 2 mg and glimepiride 4 mg. A hypoglycemic clamp was used to bring blood glucose close to 50 mg/dL before recovery was assessed. Treatment was given within a crossover design, so participants received treatments in different periods.
Comparator
Placebo was the comparator for each active-treatment estimate. The registry record also describes six treatment sequences involving placebo, glimepiride 2 mg, and glimepiride 4 mg, with a 7-day washout between periods.
Primary question
The primary question was how long it took for blood glucose to recover from hypoglycemia to euglycemia after the clamp ended, comparing glimepiride 2 mg and glimepiride 4 mg with placebo. Euglycemia was defined as 3 consecutive measurements at or above 70 mg/dL. The outcome was measured from 1 to 180 minutes after the hypoglycemic clamp.
This question concerns the measured time to a defined glucose threshold after a controlled hypoglycemic procedure. It is not a general assessment of glucose control or of clinical outcomes outside the study procedure. The registry’s brief description frames the objective as estimating recovery time following each treatment. The posted results give treatment-specific least-squares means and confidence intervals, as well as reported mean differences for the two comparisons with placebo.
The crossover structure makes within-participant observations relevant: treatment conditions were administered in separate periods rather than being assigned only as a single lasting condition. The registry record gives the sequences and washout interval, but does not report the statistical method used to account for the crossover structure. That matters when interpreting the estimates, because the treatment contrast and its uncertainty depend on how repeated observations and period effects were handled.
3. Trial Design
This was a randomized, double-masked, Phase 1 crossover study. It enrolled 10 participants with type 2 diabetes mellitus and is listed as completed. The registry record gives a study start date of 2012-07-18 and a primary completion date of 2013-01-09. Merck Sharp & Dohme LLC is listed as the sponsor.
Each sequence consisted of three treatment periods, with placebo, glimepiride 2 mg, and glimepiride 4 mg appearing in different orders. The record describes six sequences. It states that there was a 7-day washout between periods. The hypoglycemic clamp was the procedure used to maintain blood glucose close to 50 mg/dL before the recovery measurement began. Randomization and double masking describe important design features, but the registry record does not report the sequence-generation details or explain how masking was maintained.
The primary outcome results are reported for a per-protocol population consisting of participants who received drug and completed necessary post-treatment measurements for at least one treatment period. The outcome-specific participant counts were 6 for placebo, 5 for glimepiride 2 mg, and 6 for glimepiride 4 mg. These figures are treatment-specific analysis counts; the registry record does not provide a complete account of participant flow by period or explain why the counts differ across treatments.
A crossover trial can allow participants to contribute observations under more than one treatment condition. This can make the comparison sensitive to within-participant correlation, treatment order, period effects, and any residual effect from an earlier period. The washout is part of the described design, but the registry record does not report an analysis of carryover or period effects. It also does not describe the statistical model used for the primary outcome. Those omissions limit how fully the estimates can be connected to the 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.
Period 1
| Stage | Placebo → Glimepiride 2 mg → Glimepiride 4 mg | Glimepiride 2 mg → Glimepiride 4 mg → Placebo | Glimepiride 4 mg → Placebo → Glimepiride 2 mg | Placebo → Glimepiride 4 mg → Glimepiride 2 mg | Glimepiride 2 mg → Placebo → Glimepiride 4 mg | Glimepiride 4 mg → Glimepiride 2 mg → Placebo |
|---|---|---|---|---|---|---|
| STARTED | 2 | 1 | 2 | 2 | 1 | 2 |
| COMPLETED | 1 | 1 | 2 | 0 | 1 | 1 |
| NOT COMPLETED | 1 | 0 | 0 | 2 | 0 | 1 |
Reasons for not completing this period:
| Reason | Placebo → Glimepiride 2 mg → Glimepiride 4 mg | Glimepiride 2 mg → Glimepiride 4 mg → Placebo | Glimepiride 4 mg → Placebo → Glimepiride 2 mg | Placebo → Glimepiride 4 mg → Glimepiride 2 mg | Glimepiride 2 mg → Placebo → Glimepiride 4 mg | Glimepiride 4 mg → Glimepiride 2 mg → Placebo |
|---|---|---|---|---|---|---|
| Discontinued due to Hypoglycemia | 0 | 0 | 0 | 1 | 0 | 1 |
| Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
7-Day Washout
| Stage | Placebo → Glimepiride 2 mg → Glimepiride 4 mg | Glimepiride 2 mg → Glimepiride 4 mg → Placebo | Glimepiride 4 mg → Placebo → Glimepiride 2 mg | Placebo → Glimepiride 4 mg → Glimepiride 2 mg | Glimepiride 2 mg → Placebo → Glimepiride 4 mg | Glimepiride 4 mg → Glimepiride 2 mg → Placebo |
|---|---|---|---|---|---|---|
| STARTED | 1 | 1 | 2 | 0 | 1 | 1 |
| COMPLETED | 1 | 1 | 2 | 0 | 1 | 1 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Period 2
| Stage | Placebo → Glimepiride 2 mg → Glimepiride 4 mg | Glimepiride 2 mg → Glimepiride 4 mg → Placebo | Glimepiride 4 mg → Placebo → Glimepiride 2 mg | Placebo → Glimepiride 4 mg → Glimepiride 2 mg | Glimepiride 2 mg → Placebo → Glimepiride 4 mg | Glimepiride 4 mg → Glimepiride 2 mg → Placebo |
|---|---|---|---|---|---|---|
| STARTED | 1 | 1 | 2 | 0 | 1 | 1 |
| COMPLETED | 1 | 1 | 2 | 0 | 1 | 1 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
7-Day Washout
| Stage | Placebo → Glimepiride 2 mg → Glimepiride 4 mg | Glimepiride 2 mg → Glimepiride 4 mg → Placebo | Glimepiride 4 mg → Placebo → Glimepiride 2 mg | Placebo → Glimepiride 4 mg → Glimepiride 2 mg | Glimepiride 2 mg → Placebo → Glimepiride 4 mg | Glimepiride 4 mg → Glimepiride 2 mg → Placebo |
|---|---|---|---|---|---|---|
| STARTED | 1 | 1 | 2 | 0 | 1 | 1 |
| COMPLETED | 1 | 1 | 2 | 0 | 1 | 1 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The per-protocol population consisting of participants who received drug and completed the necessary post treatment measurements for at least one treatment period.
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 | All Participants |
|---|---|---|
| Participants analysed | 10 | |
| Age, Continuous | Years | 49.3 (SD 5.5) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Recovery Time From Hypoglycemia to Euglycemia, measured over From 1 to 180 minutes post hypoglycemic clamp.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 90% Confidence Interval |
| Unit | Minutes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was recovery time from hypoglycemia to euglycemia, measured in minutes. The clock began immediately after release of the hypoglycemic clamp. Recovery was defined as the point at which glucose reached 3 consecutive measurements at or above 70 mg/dL. The clamp maintained glucose close to 50 mg/dL, and the stated measurement timeframe was from 1 to 180 minutes after the clamp.
This endpoint turns a physiological recovery process into a measurable time outcome. Defining recovery through consecutive glucose measurements gives the outcome a specified threshold rather than relying on a subjective judgment. Time is relevant because the question is not only whether the threshold is reached, but how long recovery takes under each treatment condition.
The posted results report least-squares means with 90% confidence intervals. A least-squares mean is generally a model-based estimate, rather than necessarily the ordinary arithmetic average of the observations. The registry record does not describe the model or its adjustment terms, so the precise construction of these estimates is not reported in the registry record.
The endpoint is tied to a controlled clamp procedure and its defined recovery criterion. It does not by itself describe broader clinical outcomes, the frequency of hypoglycemia in daily life, or longer-term effects. The analysis population was also restricted to participants with the required post-treatment measurements for at least one period, so the endpoint estimates apply to that stated per-protocol population.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported least-squares mean recovery time was 74.49 minutes for placebo, 88.9 minutes for glimepiride 2 mg, and 109.8 minutes for glimepiride 4 mg. The corresponding reported outcome counts were 6, 5, and 6. These are estimates for the per-protocol population, not necessarily estimates for every participant enrolled.
For placebo compared with glimepiride 2 mg, the reported mean difference in final values was 14.41, with a 90% confidence interval from -22.98 to 51.80. For placebo compared with glimepiride 4 mg, the reported mean difference was 35.33, with a 90% confidence interval from -2.08 to 72.74. The registry record does not state the sign convention for these differences. Each interval extends across zero, so the reported interval estimates include values in either direction for the contrast. The intervals therefore do not establish a clear direction for either comparison.
The intervals are also broad relative to the point estimates, indicating substantial uncertainty about the size and direction of the treatment contrasts. A confidence interval describes a range of values compatible with the estimate under the statistical procedure used; it is not a guarantee that the true effect lies within the displayed limits. The registry record does not report p-values for these comparisons. It would therefore be inappropriate to replace the interval-based reading with a claim of statistical significance or non-significance based on an unreported test.
The treatment-specific estimates are not identical, but interpreting them as evidence of a dose pattern would require care. The registry record reports pairwise contrasts against placebo, not a direct comparison between glimepiride 2 mg and glimepiride 4 mg. It also does not report whether the comparisons were adjusted for the crossover design, period, sequence, or participant-level correlation. The observed estimates should not be treated as proof that one dose causes a longer recovery time than another.
Precision is limited by the modest outcome-specific counts and the uncertainty reflected in the confidence intervals. The enrollment count is 10, while the per-treatment outcome counts vary. The record does not explain the difference in those counts or provide detailed missing-data information. Because the trial is small and its analysis population is per protocol, the results are best read as estimates from this study’s measured observations, with considerable uncertainty and limited grounds for broad generalization.
The endpoint is a measured response following a hypoglycemic clamp, not a direct measure of outcomes in ordinary clinical circumstances. The estimates describe the time to the study’s specified glucose recovery criterion. They do not alone answer questions about symptoms, severe clinical events, longer-term diabetes outcomes, or effects outside the clamp procedure.
9. Statistical Methods Explained
The registry record reports treatment-specific least-squares means and 90% confidence intervals for recovery time. It also reports two mean differences in final values, each comparing placebo with an active treatment. The record does not identify the statistical method used for these comparisons, and the method is not reported in the registry record. Interpretation should therefore focus on what is posted without assuming a particular model or adjustment strategy.
What does a least-squares mean represent?
In general, a least-squares mean is an estimate produced from a statistical model. Depending on the model, it can account for specified design features or covariates and can differ from a simple arithmetic mean. The registry record does not describe the model, its terms, or the covariates used for the reported estimates. It is not possible from the registry record to determine which features were incorporated into the calculation.
That distinction is especially relevant in a crossover design. A participant may contribute measurements under multiple treatment conditions, so observations may be related rather than independent. General statistical practice may account for that dependence, as well as treatment period or sequence, but the registry record does not say whether or how these features were handled. The reported values should not be relabeled as simple unadjusted averages.
How should the confidence intervals be read?
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. The 90% intervals reported for the placebo comparisons are -22.98 to 51.80 for the glimepiride 2 mg comparison and -2.08 to 72.74 for the glimepiride 4 mg comparison. Both intervals contain zero and extend to values on either side of it. This means that the posted intervals do not resolve the direction of either contrast.
A confidence interval is not a direct probability statement about the particular treatment effect, and it does not account for analysis choices or missing information that are not represented in the method. Its interpretation depends on the model and assumptions used to calculate it. Since those details are not reported in the registry record, the intervals can be described but not fully audited from the record alone.
Why does the crossover design matter?
Generally, crossover designs compare treatment periods within participants. This can be useful because each participant may serve as a reference for their own measurements, but repeated measurements require appropriate handling of their dependence. Treatment order and period can also matter. A washout is intended to separate periods, but its presence alone does not demonstrate that carryover is absent. The record describes a 7-day washout and randomized treatment sequences; it does not report tests or model terms for period, sequence, or carryover effects.
The per-protocol definition includes participants who received drug and completed the necessary post-treatment measurements for at least one treatment period. It does not establish that every included participant completed every period. General analysis approaches can use different rules for incomplete crossover data, and those choices can affect the estimate. The registry record does not report the missing-data method, participant flow by period, or sensitivity analyses.
What can be inferred from the posted comparisons?
The two reported contrasts are placebo versus glimepiride 2 mg and placebo versus glimepiride 4 mg. Their mean differences are 14.41 and 35.33, respectively, with the 90% intervals stated above. The record provides no p-values and no method labels for these analyses. The results therefore support describing the estimated contrasts and their uncertainty, but not assigning an unreported test result or claiming that a prespecified decision threshold was met.
There are 3 outcome measures and 6 analyses recorded, while no secondary outcomes are posted. Multiple analyses can increase the chance that at least one result appears noteworthy by chance if no adjustment or hierarchy is used. General methods for handling multiplicity include prespecifying a primary comparison, adjusting inference, or interpreting analyses as exploratory. Which approach was planned or used is not reported in the registry record. The number of listed analyses alone does not establish that any particular multiplicity procedure was applied.
What does over-dispersion mean in general?
Over-dispersion is a general concern for outcomes where observed variability exceeds what a statistical model assumes. It can make standard errors too small if ignored. The primary endpoint is a time measured in minutes, and the registry record does not report an over-dispersion assessment or identify a model for which that issue can be evaluated. It would not be appropriate to claim that over-dispersion was present or that a correction was used.
The record’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration is a planning calculation, not observed power and not evidence of the trial’s original design justification. The registry record does not report the sample-size justification for the study itself. No conclusion about prospective power can be drawn from the posted outcome estimates alone.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Mean Difference (Final Values) 14.41 | -22.98 to 51.80 | not reported |
| not stated | Mean Difference (Final Values) 35.33 | -2.08 to 72.74 | not reported |
The registry record reports sponsor-posted mean differences in final values for placebo compared with glimepiride 2 mg and placebo compared with glimepiride 4 mg. Those estimates are 14.41 and 35.33, with respective 90% confidence intervals of -22.98 to 51.80 and -2.08 to 72.74. The analysis method is not identified in the record, and no p-values are reported.
A simple recalculation from treatment-level summary statistics, when available, is unadjusted and may not reproduce a model-based sponsor estimate. The posted arm results are described as least-squares means, and the registry record does not explain the model used to obtain them. A comparison derived directly from summary values would therefore not necessarily match the sponsor’s reported contrast, especially in a crossover design where within-participant measurements can be related.
No recalculated contrast values are reported in the registry record, so a numerical reconciliation cannot be made from the record. The discrepancy indicator is false, and there is no stated discrepancy requiring the sponsor’s analysis to take precedence over a recalculation. The sound reading is to keep the reported sponsor contrasts distinct from any unadjusted calculation and to recognize that the analysis details needed to reproduce the posted estimates are not reported in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry record lists 3 outcome measures and 6 analyses, with 0 secondary outcomes posted. It reports two placebo comparisons for the primary recovery-time outcome. The record does not describe a multiplicity plan, identify a prespecified hierarchy for the analyses, or state whether any adjustment was used. The presence of several analyses does not by itself show that adjustment was required or omitted; the planned inferential framework is not reported in the registry record.
In general, when multiple comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for the wider set of analyses. A prespecified primary comparison, an adjustment procedure, or an explicitly exploratory interpretation can address different aspects of this issue. The registry record does not report which, if any, of these approaches applied. The reported confidence intervals should therefore be read as the intervals attached to the stated comparisons, without assuming that they account for other analyses.
The primary outcome population was per protocol. It included participants who received drug and completed the necessary post-treatment measurements for at least one treatment period. The record gives treatment-specific counts of 6, 5, and 6 for placebo, glimepiride 2 mg, and glimepiride 4 mg. It does not report a detailed account of missing measurements, reasons for exclusions, or the number of participants with observations in each period.
Missing-data handling can matter when outcomes are unavailable for some treatment periods. General approaches may rely on different assumptions about why data are missing and how incomplete observations contribute to an estimate. The registry record does not report imputation, a missing-data model, or sensitivity analyses. It is also not reported whether all randomized participants were included in a separate intention-to-treat analysis. The available results should consequently be understood as per-protocol estimates, not as a complete account of outcomes for everyone enrolled.
12. 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 |
|---|---|---|---|
| Placebo | 0 | 9 | 0.0% |
| Glimepiride 2 mg | 0 | 6 | 0.0% |
| Glimepiride 4 mg | 0 | 7 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 3 of 9 |
| Glimepiride 2 mg | 2 of 6 |
| Glimepiride 4 mg | 4 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Glimepiride 2 mg | Glimepiride 4 mg |
|---|---|---|---|---|
| Hypoglycaemia | Metabolism and nutrition disorders | 1 of 9 | 1 of 6 | 1 of 7 |
| Headache | Nervous system disorders | 2 of 9 | 0 of 6 | 1 of 7 |
| Nausea | Gastrointestinal disorders | 0 of 9 | 2 of 6 | 0 of 7 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 9 | 1 of 6 | 0 of 7 |
| Constipation | Gastrointestinal disorders | 1 of 9 | 0 of 6 | 0 of 7 |
| Vomiting | Gastrointestinal disorders | 0 of 9 | 1 of 6 | 0 of 7 |
| Asthenia | General disorders | 0 of 9 | 0 of 6 | 1 of 7 |
| Oedema peripheral | General disorders | 1 of 9 | 0 of 6 | 0 of 7 |
| Nasopharyngitis | Infections and infestations | 0 of 9 | 0 of 6 | 1 of 7 |
| Body temperature increased | Investigations | 1 of 9 | 0 of 6 | 0 of 7 |
The registry record reports zero serious adverse events for placebo, with 9 participants at risk; zero for glimepiride 2 mg, with 6 at risk; and zero for glimepiride 4 mg, with 7 at risk. These are the posted serious-event counts for the stated groups. No top serious-event terms are listed. Death counts are not reported in the registry record.
A zero count in these groups means that no serious adverse events were recorded for the reported at-risk participants in the registry results. It does not establish that a treatment has no serious-event risk. The group sizes are limited, and the registry record does not provide additional detail about event surveillance, follow-up, or how safety groups were defined. The safety counts should also not be confused with the outcome-specific per-protocol counts, which differ.
The record separately reports other adverse events affecting 3 participants at risk of 9 in the placebo group, 2 at risk of 6 in the glimepiride 2 mg group, and 4 at risk of 7 in the glimepiride 4 mg group. These are not serious-adverse-event counts and should be kept distinct. The registry summary does not provide enough detail to assess event timing, severity beyond the serious classification, or attribution. These figures describe recorded events in the registry; they do not establish that treatment caused or prevented them.
13. What the Result Does, and Does Not, Mean
The results provide estimates of the time to the study-defined glucose recovery threshold after a hypoglycemic clamp under placebo and two glimepiride dose conditions. The treatment-specific least-squares means were 74.49 minutes for placebo, 88.9 minutes for glimepiride 2 mg, and 109.8 minutes for glimepiride 4 mg. The sponsor-reported placebo comparisons have 90% confidence intervals that include values on both sides of zero.
These findings describe measured recovery time in a small Phase 1 crossover study and in the stated per-protocol population. They do not establish a definitive direction or size for either treatment contrast. The confidence intervals indicate uncertainty, and the registry record does not provide p-values or the analysis method needed to understand fully how the estimates were constructed. A direct comparison between the two glimepiride doses is not reported.
The result is specific to a controlled hypoglycemic clamp, the study’s glucose measurement criterion, and the stated post-clamp timeframe. It is not a direct estimate of recovery in everyday settings or a summary of longer-term outcomes. The findings do not describe how often hypoglycemia occurred, nor do they establish effects on symptoms, complications, or other clinical outcomes.
The results also do not settle questions about carryover, period effects, or missing data. Although the record describes randomized treatment sequences and a 7-day washout, it does not report how these features were handled analytically. The analysis used a per-protocol population, and the reason for treatment-specific differences in outcome counts is not reported in the registry record.
In general, a trial estimate is evidence about the observations and analysis in that study, rather than a guarantee about outcomes beyond it. Here, the posted estimates and intervals are informative as a description of the study’s measurements, but their interpretation is constrained by imprecision and incomplete reporting of the analysis. They should not be turned into a claim that a treatment does or does not work.
14. Why This Trial Matters Statistically
This study illustrates the statistical features of a small crossover experiment with a time-based physiological endpoint. Participants received placebo and two active treatment conditions in different sequences, making the analysis dependent on how repeated observations within a participant are handled. The record describes randomization, double masking, treatment order, and washout, while leaving the statistical model and its treatment of period or carryover effects unreported.
The endpoint also shows why definitions matter. Recovery was not an informal judgment: it was tied to 3 consecutive glucose measurements at or above 70 mg/dL after release of a clamp that maintained glucose close to 50 mg/dL. That operational definition makes the outcome interpretable, while also limiting its meaning to the specified procedure and measurement rule.
The posted confidence intervals are central to the statistical reading. The point estimates alone might suggest a particular pattern, but both reported intervals cross zero and cover a range of possible contrast values. This illustrates why uncertainty should be read alongside an estimate, especially when the outcome counts are limited. The registry record does not provide p-values or describe the analysis method, so the intervals offer the main posted information about precision for the pairwise contrasts.
The study also illustrates the importance of distinguishing analysis populations. The enrollment count is 10, whereas the outcome results use treatment-specific per-protocol counts. Those counts are not a full description of participant flow, and the record does not report missing-data handling. Safety counts use a separate set of at-risk denominators. Keeping the outcome and safety populations distinct avoids treating unlike figures as if they described the same analysis.
Finally, the record separates design description from analysis reporting: a detailed treatment sequence and washout do not substitute for a statistical plan. For readers assessing evidence, knowing how randomization, repeated measurements, missingness, and multiple comparisons were handled is as important as knowing the observed estimates.
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 registry record does not report the statistical model used to produce the least-squares means or the placebo comparisons. It therefore does not show whether participant-level correlation, treatment period, sequence, or carryover was included in the analysis. This is a specific limitation for a crossover study, where repeated measurements can be related and treatment order may matter.
The primary analysis population was per protocol and included participants with required measurements for at least one treatment period. Treatment-specific outcome counts were 6, 5, and 6. The record does not provide participant flow by period, reasons for missing measurements, or a missing-data method. It is also not reported whether a separate analysis included all randomized participants.
The two reported contrasts have broad 90% confidence intervals that include values on both sides of zero. The registry record gives no p-values and does not describe how multiple analyses were handled. The relation between the reported intervals and any multiplicity procedure is therefore not reported in the registry record. A direct comparison between glimepiride 2 mg and glimepiride 4 mg is not posted.
The primary endpoint reflects recovery after a controlled clamp, using a specified threshold and post-clamp timeframe. The record does not provide evidence about recovery under other circumstances or longer-term outcomes. Safety reporting lists serious-event counts and other adverse-event counts, but does not give detailed event descriptions or follow-up information. Death counts are not reported in the registry record.
The study’s sample-size justification, any interim analyses, and the prespecified statistical plan are not reported in the registry record. The planning illustration described in the record is not the trial’s original design justification and should not be mistaken for observed power. These reporting gaps limit reproducibility and the scope of conclusions that can be drawn from the posted results.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253) — NCT01614769.
- Registry record last updated 2018-08-16; status last verified 2018-07.
- Results first posted 2014-02-24.
- 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.
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19. Record Summary
This completed Phase 1 study evaluated recovery time from hypoglycemia to euglycemia after a hypoglycemic clamp in participants with type 2 diabetes mellitus. It was randomized, double-masked, and used a crossover design with placebo, glimepiride 2 mg, and glimepiride 4 mg treatment periods separated by a 7-day washout.
The primary endpoint was time in minutes to 3 consecutive glucose measurements at or above 70 mg/dL after clamp release. The registry reports least-squares mean recovery times of 74.49 minutes for placebo, 88.9 minutes for glimepiride 2 mg, and 109.8 minutes for glimepiride 4 mg. The two reported placebo comparisons have 90% confidence intervals that cross zero.
The endpoint analysis was per protocol, and the registry record does not describe the analysis model, missing-data handling, or multiplicity approach. The results are specific to the study procedure and population, with uncertainty that limits definitive interpretation of the treatment contrasts.