Regulatory Request NIS in Korea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Regulatory Request NIS in Korea (NCT03642717), a registered phase not stated study. The primary outcome is Percentage of Participants With Any Adverse Events.

2. Clinical Question

The study asked whether adverse events were reported among Korean patients with type 2 diabetes mellitus who received JARDIANCE DUO® in routine clinical practice, and what effectiveness outcomes were recorded during follow-up. Its primary outcome was the percentage of participants with any adverse events from baseline until their last visit, up to 349 days. The listed effectiveness outcomes include changes in HbA1c, fasting plasma glucose, body weight, and blood pressure, as well as categories based on HbA1c response.

This is a descriptive safety question rather than a comparative treatment-effect question. Without a concurrent control group, the study can describe events observed among participants in the study, but it cannot isolate the effect of JARDIANCE DUO® from the effects of the underlying condition, other care, or differences in who was followed and for how long. Although effectiveness outcomes are listed, their numerical results are not reported in the registry record. The primary percentage and its confidence interval are also not reported in the registry record, so the size and precision of the observed event proportion cannot be assessed from the posted results.

3. Trial Design

This was a completed, non-interventional study titled “Regulatory Request NIS in Korea.” It was sponsored by Boehringer Ingelheim and concerned JARDIANCE DUO® (empagliflozin/metformin) among Korean patients with type 2 diabetes mellitus. The registry record gives an enrollment of 658 and describes routine clinical practice as the setting for monitoring safety and effectiveness. The recorded study dates are 2018-08-21 for the start and 2020-04-30 for primary completion.

The registry describes participants diagnosed with type 2 diabetes mellitus and lists JARDIANCE DUO® as the intervention. It does not describe a randomized allocation process or a concurrent control group. Allocation is not stated in the registry record. As a result, the design should be read as observational monitoring, not as a randomized comparison in which treatment groups are intended to be comparable at baseline. The record itself cautions that the arms are not a like-for-like control comparison.

The primary outcome was the percentage of participants with any adverse events from baseline, defined as Visit 1, until the last visit actually received by each patient, up to 349 days. The safety analysis set was defined as participants who signed informed consent, took JARDIANCE DUO® at least once, and had at least one physician follow-up. That set contains 620 participants in the posted safety summary, while enrollment was 658. The registry record does not explain the difference between these figures, and they should not be treated as interchangeable denominators.

Secondary outcomes included changes in HbA1c, fasting plasma glucose, body weight, systolic and diastolic blood pressure, HbA1c response thresholds, and final effectiveness assessment categories. Their presence describes what the study intended to monitor, not what was observed. Numerical outcome results and further details about recruitment, follow-up schedules, treatment exposure, or statistical planning are not reported in the registry record.

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: All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.

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: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Any Adverse Events, measured over From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days..

The primary endpoint is the percentage of participants with any adverse events during the study observation period. The period begins at baseline, identified as Visit 1, and ends at each participant’s last follow-up visit, up to 349 days. The endpoint is a binary event measure: for each participant in the defined safety analysis set, the relevant classification is whether any adverse event was recorded during that interval. The reported percentage would express how common that classification was in the analyzed group.

This type of endpoint is used to describe the observed frequency of an event in a defined population and time window. It can give a concise account of how often participants experienced at least one recorded event, while a confidence interval communicates uncertainty around the estimated percentage. The registry states that the 95% confidence interval was calculated by the Exact Method. The numerical percentage and interval, however, are not reported in the registry record. Without them, readers cannot assess the observed frequency or how precisely it was estimated.

The endpoint does not, by itself, establish that an event was caused by the study treatment. It also does not summarize the number of events per participant, the timing or duration of events, or their clinical severity. Serious adverse events are reported separately in the registry summary. The primary endpoint’s “any adverse events” wording should therefore not be conflated with the serious-event summary. Its interpretation also depends on the defined safety set and on each participant’s follow-up period, which could continue until the last visit received, up to 349 days.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a percentage, a way of expressing the share of a defined group with a recorded event. Here the relevant group is the safety analysis set, defined by informed consent, at least one dose of JARDIANCE DUO®, and at least one physician follow-up. The observation window begins at baseline and ends at the last follow-up visit actually received by each participant, up to 349 days. A percentage for this endpoint would depend on how many members of that set had at least one adverse event and on the denominator used for the analysis. The numerical primary percentage is not reported in the registry record.

A 95% confidence interval is a measure of statistical uncertainty around an estimated quantity. In general, it describes a range of values compatible with the observed data under the method’s assumptions; it is not a guarantee that an individual outcome lies within that range. The registry states that the interval for the primary percentage was calculated by the Exact Method, but does not report the interval itself. Without the estimate and interval, readers cannot assess either the observed frequency or its precision.

The phrase “Exact Method” indicates that the registry used an exact approach for the confidence interval rather than reporting a normal-approximation interval. In general, exact methods use the discrete nature of event counts when estimating uncertainty for a proportion. They can be useful when event counts are limited, because approximations based on a smooth normal distribution may be less dependable in that setting. This general description does not recover the missing primary result, and the registry does not give further details about the exact procedure or any additional statistical choices.

The study is non-interventional and has no stated randomized allocation. This changes the scope of what the statistics can answer. A proportion among treated participants is descriptive: it records the frequency observed in the analyzed group over the stated follow-up. It is not, by itself, a comparison of the treatment with an alternative. In an observational setting, participant selection, clinical decisions, other care, and follow-up can all influence the recorded outcomes. The registry cautions that arms are not a like-for-like control comparison, so arm-based contrasts should not be interpreted as randomized treatment effects.

The registry lists multiple effectiveness measures. These include change in HbA1c from baseline at the last visit, the number reaching HbA1c < 7%, the number with an HbA1c decrease of 0.5% compared with baseline, change in fasting plasma glucose, body weight, systolic blood pressure, and diastolic blood pressure, and final effectiveness assessment categories. These outcomes use different scales and answer different descriptive questions. A change outcome concerns the difference between a participant’s baseline and later measurement; a threshold outcome classifies whether a stated criterion was reached. The registry record lists the measures but does not report their numerical results or explain the analysis methods used for each.

When several outcomes are assessed, multiplicity can arise because repeated statistical tests increase the opportunity for at least one result to appear notable by chance. General approaches include prespecifying a primary outcome, adjusting for multiple comparisons, or treating secondary findings as exploratory. The registry record does not report whether any multiplicity strategy was used. It also does not report a hierarchy among secondary outcomes or identify which analyses, if any, were confirmatory. The absence of a reported strategy means readers should avoid treating a collection of listed outcomes as independent confirmation of a treatment effect.

Missing-data methods matter because participants may not have measurements at every visit or may stop being followed before the planned observation period ends. In general, analysis choices can affect which participants contribute to a change estimate and how that estimate is interpreted. The registry record does not report the amount or pattern of missing data, the handling of missing endpoint values, or whether any imputation was used. The primary outcome’s end point is the last visit actually received, so follow-up length may vary across participants; the record does not give a distribution of follow-up times.

The registry defines the safety analysis set but does not report a separate effectiveness analysis population. It also does not report a sample-size justification, a detailed statistical analysis plan, or interim analyses. The sample-size assumptions stated for planning illustrations concern an 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 planning calculations are not observed power and do not establish the study’s original design rationale. The registry record does not report that rationale or the numerical planning results.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("JARDIANCE DUO® (Empagliflozin/Metformin)")
n      <- c(620)
events <- c(74)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  JARDIANCE DUO® (Empagliflozin/Metformin)  620  74  11.9  9.5  14.8  9.6  14.7  9.6  14.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary effectiveness outcomes in addition to the primary safety endpoint. These include HbA1c changes and response categories, fasting plasma glucose, body weight, blood pressure, and final effectiveness assessment categories. Considering multiple outcomes can raise multiplicity concerns: the more results examined, the more opportunities there may be for chance findings. The registry record does not report whether the analyses were ordered in a hierarchy, whether any adjustment for multiple testing was applied, or whether the secondary outcomes were exploratory. Their numerical results are not reported in the registry record, so multiplicity cannot be evaluated against the actual findings.

Missing-data handling is also not reported. The record does not describe how unavailable measurements were treated, whether participants with incomplete follow-up were excluded from particular outcomes, or whether missing values were imputed. These details matter especially for changes from baseline, because interpretation depends on which participants have both baseline and follow-up measurements. The last-visit definition allows follow-up to end at the final visit actually received, up to 349 days; the distribution of follow-up durations is not reported.

The safety analysis set has a clear registry definition: participants signed informed consent, took JARDIANCE DUO® at least once, and had physician follow-up at least once. The posted summary gives 620 in this set, while enrollment is 658. The reason for the difference is not reported in the registry record. A separate effectiveness analysis population, outcome-specific denominators, and analysis exclusions are also not reported. Readers should therefore distinguish enrollment from the stated safety set and avoid assuming that every listed outcome used the same participants.

The registry record does not report a detailed statistical plan, an interim-analysis plan, or a sample-size justification. These absences do not show that such procedures were or were not conducted; they mean that their details cannot be assessed from the record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cerebral infarction (0.3%), myocardial infarction (0.2%), chronic gastritis (0.2%), cellulitis (0.2%), pneumonia (0.2%).

The registry’s adverse-event summary lists 620 at risk for serious adverse events, with 10 affected, and 620 at risk for other adverse events, with 0 affected. It also lists 0 deaths. These are the posted summary entries; the primary endpoint’s numerical percentage of participants with any adverse events is not reported in the registry record. The fields for serious and other events should not be assumed to provide a complete account of every event or to match the primary endpoint without additional definitions.

The serious-event terms listed are cerebral infarction (0.3%), myocardial infarction (0.2%), chronic gastritis (0.2%), cellulitis (0.2%), pneumonia (0.2%), and ankle fracture (0.2%). The record does not provide counts alongside these term percentages or clarify whether a participant may appear under more than one term. The percentages should therefore be read as the registry presents them, not added to produce a combined rate.

These entries describe events recorded during monitoring; they do not establish that JARDIANCE DUO® caused the events. The record does not report adjudication details, event timing, participant-level clinical context, or a comparison group suitable for estimating an excess risk. The listed 0 deaths is a summary entry, not proof that the treatment has no mortality risk. The size and precision of the primary any-adverse-event result cannot be judged because its percentage and confidence interval are not reported in the registry record.

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

The registry record documents a completed non-interventional study of JARDIANCE DUO® in Korean patients with type 2 diabetes mellitus. It states that 658 participants were enrolled and defines a safety analysis set of 620. The primary outcome was the percentage with any adverse events between baseline and the last visit, up to 349 days. A 95% confidence interval was calculated by the Exact Method, but neither the percentage nor the interval is reported in the registry record. The posted results therefore do not allow readers to quantify the primary outcome or judge its precision.

The record also lists serious-event summary entries and selected event terms with percentages. These are descriptions of what was recorded, not evidence that the treatment caused the events. Without a randomized control comparison, the study cannot determine whether observed events or changes would have been different under another treatment. Its routine-practice setting can be relevant to safety monitoring, but observations in one treated group do not separate treatment effects from disease, other care, participant characteristics, or follow-up patterns.

Effectiveness outcomes are named, including HbA1c, fasting plasma glucose, body weight, blood pressure, and HbA1c response thresholds. Their numerical results are not reported in the registry record. The endpoint list alone does not establish whether participants improved, remained stable, or worsened, nor does it establish the size or precision of any change.

Accordingly, the record is useful for understanding the study’s intended monitoring questions, population definition, and reported safety summaries. It does not provide enough numerical outcome information to evaluate the primary event percentage or the effectiveness outcomes. It also does not report missing-data methods, multiplicity procedures, or a detailed statistical plan. Those limitations constrain interpretation; they are not evidence that unreported outcomes were favorable or unfavorable.

14. Why This Trial Matters Statistically

Non-interventional studies address questions in routine clinical settings, where treatment and follow-up occur as part of ordinary care rather than through a stated randomized allocation. This Korean study was designed to monitor safety and effectiveness of JARDIANCE DUO® among people with type 2 diabetes mellitus. Its focus makes clear an important statistical distinction: describing outcomes observed in a treated group is not the same as estimating a causal effect against a comparable control group.

The primary endpoint is a percentage of participants with any adverse events, tied to a defined safety analysis set and a follow-up period ending at each participant’s last visit, up to 349 days. This makes the denominator and observation window central to interpretation. The safety set contains 620 participants, compared with an enrollment of 658, but the reason for that difference is not reported in the registry record. The record states that a 95% confidence interval was calculated, yet omits its value and the primary percentage. This illustrates why reporting the estimate and its uncertainty is necessary for readers to assess a descriptive result.

The registry also lists a broad set of effectiveness measures. Multiple measures can represent different clinical dimensions, but interpretation requires outcome values, denominators, missing-data details, and clarity about how multiple analyses were handled. Those details are not reported in the registry record. In their absence, outcome listings should not be mistaken for evidence of a measured benefit or harm.

Statistically, the study matters as an example of both the value and limits of observational safety monitoring. It records a real-world monitoring question and specifies a population and endpoint, while the lack of a like-for-like comparator restricts causal claims. Complete numerical reporting and transparent methods are needed to assess how precisely the observed outcomes were estimated and how far they can be generalized.

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 study is non-interventional, and the registry record does not state allocation. It identifies no like-for-like control comparison. Therefore, observed safety or effectiveness outcomes cannot be attributed to JARDIANCE DUO® by comparison with an alternative treatment. Differences in participants, clinical management, other care, and follow-up may influence descriptive results.

The primary endpoint percentage and its 95% confidence interval are not reported in the registry record. This prevents assessment of both the observed frequency of any adverse event and its precision. The registry gives 620 participants in the safety analysis set and 658 enrolled, but does not explain the difference. It also does not report outcome-specific denominators or a separate effectiveness analysis population.

Follow-up was defined through each participant’s last visit, up to 349 days. The registry record does not report how follow-up duration varied, how many participants had incomplete follow-up, or how missing measurements were handled. These omissions matter when interpreting changes from baseline and event frequencies across participants with potentially different observation periods.

Numerical results for the listed effectiveness outcomes are not reported in the registry record. The record also does not report multiplicity procedures, a detailed statistical analysis plan, a sample-size justification, or interim analyses. Serious-event terms are listed with percentages, but counts and further coding or adjudication details are not reported. Together, these limitations leave the magnitude, precision, and causal interpretation of outcomes difficult to evaluate from the registry record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Regulatory Request NIS in Korea — NCT03642717.
• Registry record last updated 2021-05-21; status last verified 2021-04.
• Results first posted 2021-05-21.
• 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

NCT03642717 is a completed, non-interventional study sponsored by Boehringer Ingelheim. It monitored safety and effectiveness of JARDIANCE DUO® (empagliflozin/metformin) in Korean patients with type 2 diabetes mellitus in routine clinical practice. Enrollment was 658; the safety analysis set included 620 participants. The recorded start date was 2018-08-21, and primary completion was 2020-04-30.

The primary outcome was the percentage of participants with any adverse events from baseline until the last visit, up to 349 days. The registry states that a 95% confidence interval was calculated by the Exact Method, but the numerical percentage and interval are not reported in the registry record. The posted safety summary lists 10 affected for serious adverse events and 0 deaths, with selected serious-event terms and percentages. Effectiveness outcomes are listed, but their numerical results are not reported.

No randomized allocation or like-for-like control comparison is described. The registry record also does not report missing-data handling, multiplicity procedures, a detailed statistical plan, or a sample-size justification.