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 Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events (NCT01959529), a randomized phase 3 study. The primary outcome is Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01959529 |
| Phase | Phase 3 |
| Condition | Diabetes, Diabetes Mellitus, Type 2 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 7637 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novo Nordisk A/S |
| Results posted | Yes |
2. Clinical Question
Population
Participants had type 2 diabetes and were at high risk of cardiovascular events. The registry describes the primary analysis population as the full analysis set, which included all randomised subjects. Enrollment was 7637. Further eligibility details are not reported in the registry record.
Intervention
Participants were assigned to insulin degludec. They continued their current antidiabetic therapy, except that any basal insulin component was replaced by the investigational product.
Comparator
The comparison group was assigned to insulin glargine. As in the other group, participants continued their current antidiabetic therapy apart from replacement of any basal insulin component by the investigational product.
Primary question
The trial asked whether the time from randomisation to a first event adjudication committee-confirmed major adverse cardiovascular event differed between the insulin groups. MACE was defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The registry record does not report the comparative effect estimate or its uncertainty in the registry record for this analysis.
3. Trial Design
This was a phase 3, randomized, double-masked, parallel-group trial comparing insulin degludec with insulin glargine. The trial was conducted globally, according to the brief summary. Enrollment was 7637. The registry lists the condition as diabetes and type 2 diabetes mellitus.
In both groups, participants continued their existing antidiabetic therapy, with any basal insulin component replaced by the assigned investigational product. The registry describes the primary analysis population as the full analysis set, including all randomised subjects. Additional details about the randomisation procedure, allocation concealment, masking procedures, and eligibility criteria are not reported in the registry record.
The trial began on 2013-10-29, and primary completion was recorded as 2016-10-16. Its primary cardiovascular outcome was measured from randomisation to the first qualifying event, with follow-up ending at each participant’s individual end-of-trial date. The primary outcome description states a maximum patient-year observation of 2.75 years. It also describes the trial as event driven and planned to last up to a maximum of 60.5 months; the actual duration from the first subject’s first visit to the last subject’s last visit was 35.6 months. The maximum duration for a single subject was 33.1 months.
The registry record does not provide details of the planned event target, the protocol’s statistical analysis plan, or the procedures used to manage changes in treatment. Those details should not be inferred from the design description alone.
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 | Insulin Degludec | Insulin Glargine |
|---|---|---|
| STARTED | 3818 | 3819 |
| Exposed | 3809 | 3806 |
| COMPLETED | 3742 | 3747 |
| NOT COMPLETED | 76 | 72 |
Reasons for not completing this period:
| Reason | Insulin Degludec | Insulin Glargine |
|---|---|---|
| Adverse event (not hypoglycaemia) | 0 | 1 |
| Lost to Follow-up | 4 | 1 |
| Other | 70 | 68 |
| Hypoglycaemia | 1 | 1 |
| Lack of glycaemic control | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was based on the FAS, which included all randomised subjects.
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: Baseline analysis was based on the full analysis set (FAS), which included all randomised subjects.
| Characteristic | Unit | Insulin Degludec | Insulin Glargine | Total |
|---|---|---|---|---|
| Participants analysed | 3818 | 3819 | 7637 | |
| Age, Continuous | years | 64.9 (SD 7.3) | 65.0 (SD 7.5) | 65.0 (SD 7.4) |
| Sex: Female, Male: Female | Participants | 1422 | 1437 | 2859 |
| Sex: Female, Male: Male | Participants | 2396 | 2382 | 4778 |
| HbA1c | percentage of HbA1c | 8.44 (SD 1.63) | 8.41 (SD 1.67) | 8.43 (SD 1.65) |
6. Primary Endpoint
The registry lists the primary outcome as Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke, measured over From randomisation to individual end of trial date (maximum patient year observation: 2.75 years).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was time from randomisation to the first event adjudication committee-confirmed major adverse cardiovascular event. The composite included cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The registry description says that qualifying events with an adjudicated onset date between randomisation and the individual end-of-trial date were included, with both endpoint dates included.
A time-to-first-event endpoint accounts for when an initial event occurs as well as whether one occurs during follow-up. This is useful when participants can have different observation periods, as described in this trial. A composite endpoint combines several clinically distinct event types into one measure. That can provide a broader summary of cardiovascular events, but it also means an overall result would not, by itself, show whether each component had a similar pattern. Component-specific comparative results are not reported in the registry record details available for this analysis.
The primary outcome is described as the number of subjects experiencing a first qualifying MACE, while its timeframe and description concern time to event. A count of participants with events alone does not convey event timing or account for censoring. The statistical analysis used to compare time to event, and its estimate of the difference between groups, are not reported in the registry record details.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies an important comparative question: cardiovascular events among people with type 2 diabetes at high cardiovascular risk who were assigned to insulin degludec or insulin glargine. It defines the primary outcome as time from randomisation to a first adjudicated MACE, comprising cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. However, the registry entries available for this analysis do not include the primary outcome counts by group, a relative or absolute effect estimate, a confidence interval, or a p-value. The direction and precision of the comparative result therefore cannot be described.
The record’s primary outcome description includes counts of participants experiencing a first event, but a count alone is not a treatment comparison. Even if group-specific counts were available, interpreting a time-to-event outcome would also require attention to how long participants were followed and how incomplete follow-up was handled. The record describes individual end-of-trial follow-up and gives trial-duration information, but does not report the comparative time-to-event analysis in the registry record for this analysis.
Consequently, the registry information does not establish whether the groups had similar or different MACE experience, nor does it indicate how precisely any difference was estimated. A confidence interval, if reported, would communicate a range of effect values compatible with the data under the analysis assumptions; its width would help readers assess precision. No such interval is reported in the registry entries. A p-value is also not reported, and its absence cannot be replaced by interpretation of the study’s size or design.
The serious adverse event information is descriptive. The registry lists 1473 participants in the insulin degludec group and 1517 in the insulin glargine group as affected by serious adverse events, with 3818 and 3819 at risk, respectively. These figures should be read as reported group counts, not as a formal comparative safety estimate. The record also lists serious event terms with percentages, but the denominator and the basis for those percentages are not specified in the registry entries. No conclusion about comparative risk or causation follows from those figures alone.
Planning illustrations based on an observed effect, when displayed with the analysis, are not observed power and are not the trial’s original sample-size justification. The assumptions described for those illustrations are not evidence of the design rationale. The trial’s own sample-size justification is not reported in the registry record.
9. Statistical Methods Explained
Several statistical ideas help interpret the stated endpoint, but the registry entries available for this analysis do not identify the exact primary analysis method. The distinction between general methodological explanation and trial-specific reporting is important: a method that is often used for an endpoint is not necessarily the method used in this trial.
What does a time-to-event outcome represent?
A time-to-event outcome records the time until an event of interest, rather than only whether the event occurred. In this trial, the event of interest was the first event adjudication committee-confirmed MACE after randomisation. The endpoint description specifies that the qualifying event had to occur by the participant’s individual end-of-trial date. Participants may therefore contribute different amounts of follow-up.
In general, time-to-event methods can use the event timing and account for participants whose event has not been observed by the end of their follow-up. Such participants are often described as censored: their observed follow-up contributes information up to the point observation ends, without assuming that an event occurred afterward. How censoring was defined and handled in this trial is not reported in the registry record.
Why is a simple event count not the full analysis?
A count gives the number of participants recorded with an event, but it does not show when events occurred or how much follow-up each group contributed. When follow-up differs, the same count can represent different event patterns. Time-to-event analysis is designed to use more of this information, subject to its assumptions. The registry outcome description supplies an event count measure and a time-to-event definition, but the analysis method and comparative estimate are not reported in the registry record for this analysis.
For time-to-event comparisons, analysts may report a relative measure such as a hazard ratio, an absolute measure such as a difference in event probability at a chosen time, or another summary. These measures answer different questions and depend on their definitions and assumptions. None of the comparative measures or associated uncertainty estimates is reported in the registry entries. It would therefore be inappropriate to infer a particular model or reconstruct a treatment effect from the design description.
What does event adjudication add?
The primary endpoint required confirmation by an event adjudication committee. In general, adjudication uses a defined review process to determine whether reported events meet the endpoint criteria. This can support consistent outcome classification, especially when an endpoint combines different event types. The committee’s procedures, review blinding, and adjudication criteria beyond the listed MACE components are not reported in the registry record.
How should uncertainty be read?
In general, a confidence interval describes the uncertainty around an estimated effect under the statistical model and analysis assumptions. A narrow interval indicates greater precision than a wide interval, but precision is not the same as importance or proof. A p-value, when reported, describes how compatible the observed data are with a specified null model under the test assumptions; it does not measure the probability that a treatment effect is true. The primary effect estimate, confidence interval, and p-value are not reported in the registry record for this analysis.
Randomisation supports a fair comparison on average by assigning participants to groups through a chance process. It does not guarantee identical group characteristics in a particular trial, and it does not remove the need to account for follow-up, outcome ascertainment, and the prespecified analysis. The registry identifies the study as randomized and double-masked, but does not provide enough detail to describe the exact randomisation or masking procedures.
What do the planning illustrations mean?
In general, a sample-size calculation uses assumptions about the effect to detect, the allocation, the significance level, and the statistical method to illustrate the number of participants or events that might be needed. The registry entries describe planning illustrations based on fractions of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event illustrations, the described quantity is a total event count; for other outcomes, it is participants per arm.
These are planning illustrations, not the original design justification and not observed power. Observed power is not a useful substitute for the estimated effect and its uncertainty after results are available. The actual numerical planning illustrations are not included in the registry record for this analysis. The trial’s original sample-size assumptions and justification are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry entries list the primary MACE outcome and secondary outcomes concerning the number of event adjudication committee-confirmed severe hypoglycaemic episodes, whether a participant experienced at least one such episode, and change in glycosylated haemoglobin. The record indicates four outcome measures and three analyses, but does not give enough detail to establish the full analysis hierarchy or how the listed outcomes relate to all analyses.
When multiple outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. General approaches to this issue include prespecifying a primary outcome, controlling the testing sequence, or adjusting interpretation for multiple comparisons. The registry entries do not report whether or how multiplicity was addressed, whether there were interim analyses, or which outcomes were formally confirmatory. These details are not reported in the registry record.
The primary analysis population is described as the full analysis set, including all randomised subjects. The registry entries do not specify how missing outcome information, withdrawal, loss to follow-up, or other incomplete observations were handled. They also do not report imputation procedures, sensitivity analyses, or whether analyses used additional populations. For a time-to-event endpoint, the handling of participants whose follow-up ends before a MACE is observed is especially relevant, but the specific censoring rules and any checks of assumptions are not reported.
The absence of these details limits assessment of how robust the result would be to alternative analysis choices. It does not show that a particular procedure was or was not used; it means that the procedure is not reported in the registry record details available for this analysis.
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 |
|---|---|---|---|
| Insulin Degludec | 1473 | 3818 | 38.6% |
| Insulin Glargine | 1517 | 3819 | 39.7% |
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 |
|---|---|
| Insulin Degludec | 0 of 3818 |
| Insulin Glargine | 0 of 3819 |
Most frequent serious adverse event terms
| Event term | Organ system | Insulin Degludec | Insulin Glargine |
|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | 134 of 3818 | 143 of 3819 |
| Acute myocardial infarction | Cardiac disorders | 98 of 3818 | 115 of 3819 |
| Pneumonia | Infections and infestations | 90 of 3818 | 90 of 3819 |
| Coronary artery disease | Cardiac disorders | 80 of 3818 | 89 of 3819 |
| Angina unstable | Cardiac disorders | 87 of 3818 | 79 of 3819 |
| Acute kidney injury | Renal and urinary disorders | 70 of 3818 | 95 of 3819 |
| Myocardial infarction | Cardiac disorders | 48 of 3818 | 66 of 3819 |
| Cellulitis | Infections and infestations | 52 of 3818 | 61 of 3819 |
| Hypoglycaemia | Metabolism and nutrition disorders | 64 of 3818 | 49 of 3819 |
| Fall | Injury, poisoning and procedural complications | 54 of 3818 | 55 of 3819 |
Serious events with the highest arm-level rate: cardiac failure congestive (3.7%), acute myocardial infarction (3.0%), acute kidney injury (2.5%), pneumonia (2.4%), coronary artery disease (2.3%).
The registry lists serious adverse event counts for both groups. For insulin degludec, 1473 participants were affected among 3818 at risk; for insulin glargine, 1517 were affected among 3819 at risk. These are descriptive counts as recorded. They do not, by themselves, establish a difference between groups or whether an event was caused by the assigned treatment.
The record also lists serious adverse event terms and their displayed percentages: cardiac failure congestive, 3.7%; acute myocardial infarction, 3.0%; acute kidney injury, 2.5%; pneumonia, 2.4%; coronary artery disease, 2.3%; and angina unstable, 2.3%. The denominator, whether these percentages refer to participants or events, and whether terms overlap are not reported in the registry entries available for this analysis. These percentages should therefore be interpreted as registry-listed descriptions, not as directly comparable risks.
Deaths are not reported in the adverse event fields available for this analysis. The definitions, collection period, and comparative statistical analysis for serious adverse events are also not reported in the registry record details. Serious adverse event counts are not the same as the primary adjudicated MACE endpoint, even though some event types may be clinically related.
12. What the Result Does, and Does Not, Mean
This trial was designed to compare insulin degludec with insulin glargine on a cardiovascular endpoint in participants with type 2 diabetes at high risk of cardiovascular events. Its primary endpoint focused on the time to a first adjudicated event in a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The randomized, double-masked, parallel-group design describes how the comparison was organised, while the endpoint description identifies what it aimed to measure.
The registry entries available for this analysis do not include the primary outcome results by group or a comparative effect estimate with uncertainty. They therefore do not support a conclusion about the direction, magnitude, or precision of the cardiovascular comparison. The design and enrollment alone cannot answer the outcome question. Nor can the serious adverse event counts replace the missing primary analysis: they are descriptive figures, and the record details do not report a formal safety comparison.
Even when an overall composite result is available, it should be interpreted in context. A composite combines distinct event types, so an overall estimate does not necessarily imply that each component had the same frequency or treatment pattern. The registry entries do not provide component-specific comparative estimates. Follow-up also varied by participant, as reflected in the individual end-of-trial date and the stated duration information, making the analysis method and handling of incomplete follow-up important.
The registry record is useful for identifying the trial’s design, population, intervention groups, and outcome definitions. It does not provide all information needed to judge the statistical result. The statistical analysis plan, multiplicity strategy, missing-data methods, and comparative effect estimates are not reported in the registry record for this analysis. Such omissions should be treated as limits on interpretation, rather than grounds to infer what the unreported analyses found.
Planning illustrations based on an observed effect, if consulted, describe hypothetical sample sizes under stated assumptions. They are not evidence of what was observed, do not establish precision, and are not observed power. The original sample-size justification is not reported in the registry record.
13. Why This Trial Matters Statistically
Statistically, the trial brings together a randomized comparison and an outcome that depends on both event occurrence and timing. That combination makes it important to distinguish a simple participant count from a time-to-event estimate. The endpoint’s definition is clear at a broad level: the first adjudicated MACE after randomisation, comprising cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Its follow-up ends at each participant’s individual end-of-trial date.
The global trial involved 7637 participants and compared two basal insulin strategies while allowing participants to continue their current antidiabetic therapy apart from replacement of any basal insulin component. The design makes the comparison relevant to the stated cardiovascular safety question, but the design alone does not determine what the results show. Estimation, uncertainty, event timing, and the handling of incomplete observation are all central to interpreting a time-to-event comparison.
This record also illustrates why outcome definitions and analysis reporting need to be read together. An endpoint description may identify the events of interest, but readers also need the group-level results, an effect estimate, its uncertainty, and enough statistical-method detail to assess interpretation. Those comparative primary results and details are not reported in the registry record for this analysis.
Finally, safety summaries and primary outcomes should not be conflated. Serious adverse event counts provide descriptive information, while the primary endpoint is a specifically adjudicated cardiovascular composite. The registry-listed percentages for serious event terms have no reported denominator in the registry entries. Careful separation of outcome types, denominators, and analyses is necessary to avoid claims beyond what the record supports.
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 the primary comparison is that the registry entries available for this analysis do not include group-specific primary event counts, the effect estimate, a confidence interval, or a p-value. Although the outcome definition and time frame are described, the comparative result cannot be evaluated for direction or precision from these registry entries.
The primary endpoint description combines a count of participants with a time-to-first-event framework. The record does not report the statistical model, censoring rules, treatment of incomplete follow-up, or checks of assumptions. This matters because participants could have different observation durations, and the analysis method determines how timing and follow-up contribute to the comparison.
The registry identifies the full analysis set as all randomised subjects, but the registry entries do not describe the handling of missing data, withdrawals, or additional analysis populations. They also do not report the multiplicity strategy, interim analyses, or the protocol’s statistical analysis plan. These gaps restrict assessment of how analysis choices may affect interpretation; they do not establish that any particular procedure was omitted.
The serious adverse event data are also limited. The record lists affected-participant counts and serious event terms with percentages, but the denominator and basis of those percentages are not reported in the registry entries. Deaths are not reported in the adverse event fields. These descriptions cannot be treated as a complete comparative safety analysis.
Finally, the registry entries do not provide the original sample-size justification. Any planning illustrations based on observed effects are hypothetical calculations under stated assumptions, not a substitute for the trial’s design rationale or for the actual treatment-effect estimate and its uncertainty.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events — NCT01959529.
- Registry record last updated 2019-07-24; status last verified 2019-07.
- Results first posted 2017-11-17.
- 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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18. Record Summary
NCT01959529 is a completed phase 3, randomized, double-masked, parallel-group trial comparing insulin degludec with insulin glargine in participants with type 2 diabetes at high risk of cardiovascular events. Enrollment was 7637. Participants continued their current antidiabetic therapy apart from replacement of any basal insulin component by the assigned product.
The primary outcome was time from randomisation to the first event adjudication committee-confirmed MACE: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The primary analysis population was the full analysis set, including all randomised subjects. The registry record details available for this analysis do not report the comparative primary outcome estimate or its uncertainty. Serious adverse event counts are listed descriptively, while their comparative interpretation and the denominator for listed term percentages are not reported.