A Study for Post-Marketing Surveillance of Nesina® Tablet Monotherapy or Combination Therapy in Participants With Type 2 Diabetes (T2DM) in South Korea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study for Post-Marketing Surveillance of Nesina® Tablet Monotherapy or Combination Therapy in Participants With Type 2 Diabetes (T2DM) in South Korea (NCT04980040), a registered phase not stated study. The primary outcome is Percentage of Participants With Serious Adverse Events (SAEs).

2. Clinical Question

This is a post-marketing safety question rather than a randomized comparison of treatment strategies. The record describes surveillance of participants receiving alogliptin for type 2 diabetes and lists adverse events, including serious adverse events and serious adverse drug reactions, as the main safety focus. Secondary outcomes include HbA1c levels, fasting blood glucose levels, the percentage with HbA1c < 7.00%, and an overall improvement and final effectiveness assessment. The numerical results for those secondary outcomes are not reported in the registry record.

3. Trial Design

This completed study is identified as a post-marketing surveillance protocol for Nesina® tablet, either as monotherapy or combination therapy, in participants with type 2 diabetes in South Korea. The registry lists Takeda as the sponsor and describes participants who took Nesina® as prescribed by their physician. The intervention is alogliptin benzoate. The record does not describe a randomized allocation process, and it identifies only one group, Nesina® Tablet. It therefore does not present a concurrent control group for a like-for-like treatment comparison.

The registry lists enrollment of 3623. The primary endpoint uses a Safety Set defined as participants who had been administered the study drug and completed follow-up. For the serious adverse event outcome, the registry lists 3131 participants at risk. The reason the enrollment figure and the outcome population differ is not reported in the registry record. The record does not provide further detail about recruitment, the number of sites, eligibility criteria, or how participants entered the surveillance cohort.

The study start is listed as 2014-04-19, and primary completion as 2019-08-30; the status is COMPLETED. The primary safety observation window runs from first dose up to 30 days after the last dose, with the timeframe described as up to 79.77 weeks. The registry does not report how treatment duration varied across participants or how follow-up was conducted in practice.

The stated purpose is to evaluate safety by determining incidence rates for adverse events, including serious adverse events and serious adverse drug reactions, unexpected events and reactions not reflected in precautions for use, known adverse drug reactions, non-serious adverse drug reactions, and other safety-related information. Eight outcome measures are listed, but registered analysis entries are not reported. The study's sample-size justification, interim analyses, detailed statistical analysis plan, and procedures for handling missing observations 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: This post-marketing surveillance (PMS) study was conducted during a re-examination period of approximately 5 years and 4 months to investigate the safety and efficacy of monotherapy or combination therapy with alogliptin in participants with type 2 diabetes in routine care settings.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Set included all participants who had been administered the study drug and completed the follow-up.

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 included participants who were treated with the surveillance drug at least once and completed the follow-up for safety.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Serious Adverse Events (SAEs), measured over From first dose of study drug up to 30 days post last dose of study drug (Up to 79.77 weeks).

The primary endpoint is the percentage of participants with serious adverse events. The registry defines a serious adverse event by outcomes or significance: death, initial or prolonged inpatient hospitalization, a life-threatening experience involving immediate risk of dying, persistent or significant disability or incapacity, congenital anomaly, or an event deemed significant for another reason. This definition classifies events by seriousness, not simply by how uncomfortable or frequent a symptom may be.

The outcome is relevant to post-marketing safety surveillance because it describes the occurrence of serious events during exposure and the stated post-treatment observation period. It does not, by itself, establish that a drug caused an event. In a surveillance record without a like-for-like control group, the endpoint is a descriptive safety measure; the registry record does not describe a method for separating treatment-related events from events that occurred for other reasons.

The specified timeframe begins at the first dose and continues through 30 days after the last dose, with the listed maximum duration of 79.77 weeks. The registry says the 95% confidence interval was calculated using an exact method. It lists 37 participants with serious adverse events among 3131 in the outcome population, but does not report the confidence interval limits in the registry record. The interpretation should therefore retain both the observed count and the uncertainty information that would be conveyed by the interval, while recognizing that the interval values are not reported.

The registry also lists serious event terms and other safety outcomes. These complement the primary percentage by describing the types of events recorded, but they do not replace the endpoint definition or provide a causal comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: whether a participant experienced a serious adverse event during the specified observation window. A percentage summarizes the share of the defined safety population with the event. In general, binary outcomes are useful for communicating how many people experienced an event, but a percentage does not show when events occurred, how many events each participant had, or whether an event was caused by treatment.

What does the confidence interval add?

The registry specifies a 95% confidence interval calculated using an exact method. In general, a confidence interval describes the uncertainty associated with an estimate under a statistical model. Exact methods are often used for binary outcomes when event counts are limited, because they rely on the probability model for the observed count rather than a large-sample approximation. The registry does not report the interval limits, so the range of values compatible with the analysis cannot be assessed from the record. The stated confidence level is not a guarantee about an individual participant's outcome.

The count and denominator need to be read together with the endpoint definition and analysis population. The record lists 37 participants with serious adverse events among 3131 at risk. Those figures describe the registry's safety set; they should not be silently extended to the enrollment population. The Safety Set is defined as participants who were administered the study drug and completed follow-up. Why the enrollment figure differs from the safety-set denominator is not reported in the registry record.

Why does study design matter?

Post-marketing surveillance can describe events observed among people using a treatment in the setting described by the record. A one-group description does not estimate what would have happened to the same participants under a different treatment or no treatment. In general, a comparison group can help distinguish background event occurrence from differences associated with treatment, but the registry describes one group and no randomized comparison. Events may reflect the underlying condition, other health circumstances, concomitant treatments, or other causes; the posted counts alone cannot separate these explanations.

Random allocation, when used, aims to make groups comparable on average by assigning treatment through chance. The record does not report randomized allocation, and its own description cautions that the arms are not a like-for-like control comparison. Accordingly, the primary finding should be read as observed safety information, not as a treatment effect relative to a comparator. The record does not report an adjusted analysis that would address differences among participants.

How should the adverse-event terms be read?

The primary endpoint counts participants with serious adverse events according to the seriousness definition in the record. The listed serious-event terms provide additional descriptive detail. The displayed percentages for Hyperglycaemia, Diabetes mellitus aggravated, Abscess, Pulmonary carcinoma, and Anorexia are each 0.1%; Tenosynovitis is displayed as 0.0%. A percentage rounded to one decimal place may conceal a small nonzero underlying value. Because term-specific counts are not reported, the listed percentages should not be converted into counts or treated as exact unrounded risks.

Seriousness and causality are distinct concepts. Seriousness is determined by the event's consequences or significance under the stated definition. Causality asks whether the treatment produced the event. The registry's summary of serious adverse events does not establish causality. Although the stated surveillance purpose includes serious adverse drug reactions and other adverse drug reaction categories, the primary endpoint is serious adverse events. The record does not provide enough detail to infer how each listed term was judged for relatedness.

What do the planning illustrations represent?

Any sample-size illustrations associated with the posted results are planning exercises, not features of this completed surveillance study's original design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such calculations ask what sample size might be needed under specified assumptions for a future comparison. They do not show that the surveillance study had that design, and they are not observed power. The record does not report the study's own sample-size justification or a randomized two-arm comparison. Since the observed effect and illustration values are not reported in the registry record, no numerical planning estimate should be inferred.

For general context, over-dispersion occurs when variability in observed outcomes exceeds what a simple model assumes. It can make standard errors too small if the extra variation is ignored. The registry does not report an over-dispersion assessment or a model for repeated events, and the primary endpoint is a participant-level percentage rather than a reported event-rate model. No claim about over-dispersion handling can therefore be made for this analysis.

The registry lists eight outcome measures and zero registered analysis entries. That does not establish which analyses may have been conducted outside the registry; it means the record does not report analysis entries. The detailed statistical plan, missing-data procedures, interim analyses, and multiplicity strategy are not reported in the registry record. These omissions limit evaluation of prespecification and of how results across multiple outcomes were interpreted.

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("Nesina® Tablet")
n      <- c(3131)
events <- c(37)
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  Nesina® Tablet  3131  37  1.2  0.8  1.6  0.9  1.6  0.9  1.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary serious adverse event outcome and secondary measures concerning HbA1c, fasting blood glucose, an HbA1c threshold, and overall improvement and final effectiveness assessment. It lists zero registered analysis entries. The statistical plan and the method, if any, for controlling or interpreting multiplicity are not reported in the registry record.

Multiplicity matters when several outcomes or analyses are considered: the more opportunities there are to identify a result that appears notable, the more important it becomes to distinguish prespecified questions from exploratory findings. This is a general statistical concern, not evidence that a particular error occurred in this surveillance study. Since numerical results for the secondary outcomes and detailed analysis procedures are not reported, their relationship to the primary safety question cannot be assessed.

The Safety Set includes participants who received the study drug and completed follow-up. The registry lists enrollment of 3623 and an at-risk population of 3131 for the serious adverse event outcome, but the reason for the difference is not reported in the registry record. The record does not describe missing-data methods, loss to follow-up, or how participants who did not complete follow-up contributed to other analyses. Consequently, the reported primary safety result should be understood as applying to the defined Safety Set, not presumed to represent every enrolled participant.

The record also does not report interim analyses, a detailed sample-size justification, or a full statistical analysis plan. These omissions do not change the recorded count, but they constrain assessment of how endpoints and analysis populations were chosen and how uncertainty across outcomes was managed.

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: hyperglycaemia (0.1%), diabetes mellitus aggravated (0.1%), abscess (0.1%), pulmonary carcinoma (0.1%), anorexia (0.1%).

For the Nesina® Tablet group, the registry lists 37 participants with serious adverse events among 3131 at risk. The primary endpoint is the percentage of participants with at least the defined serious-event outcome, during the period from first dose through 30 days after the last dose. The stated maximum timeframe is up to 79.77 weeks. The registry specifies an exact-method 95% confidence interval, but its limits are not reported in the registry record.

The recorded death count is 0. Death is one of the outcomes included in the registry's definition of a serious adverse event, but the broader serious-event category also includes hospitalization, life-threatening experience, persistent or significant disability or incapacity, congenital anomaly, and other events deemed significant. A zero in the deaths field therefore does not mean there were no serious adverse events.

Listed serious-event terms include Hyperglycaemia, Diabetes mellitus aggravated, Abscess, Pulmonary carcinoma, and Anorexia, each displayed as 0.1%; Tenosynovitis is displayed as 0.0%. These are rounded displayed percentages, and term-specific counts are not reported in the registry record. A displayed 0.0% should not be read as proof of zero cases. These descriptive records also do not, on their own, establish that alogliptin caused any event.

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

The result describes serious adverse events recorded among participants in the defined Safety Set during the stated observation period. The registry lists 37 affected participants among 3131 at risk. This is useful as a description of the monitored group, but the confidence interval limits are not reported in the registry record, so the numerical precision of the percentage cannot be assessed from the record.

The findings do not estimate a difference between Nesina® and another treatment. The registry describes one group, does not state an allocation process, and cautions that this is not a randomized comparison or a like-for-like control comparison. Without a suitable comparator, the observed events cannot be attributed to treatment simply because they occurred during surveillance. Nor does the count show what event frequency would have occurred in the same population without alogliptin.

The record's serious-event definition includes several types of clinical consequence, not just death. The listed death count is 0, while the serious adverse event count is 37. These statements refer to different levels of the endpoint and should not be conflated. The listed event terms and percentages add descriptive context, but term-specific counts and causality assessments are not reported in the registry record. The displayed 0.0% for Tenosynovitis is rounded and does not establish that no cases occurred.

The record names secondary measures concerning HbA1c and fasting blood glucose, but their numerical results are not reported in the registry record. Therefore the endpoint list alone does not establish whether those measures changed or how participants were classified on the effectiveness assessments. The stated purpose and outcome names should not be treated as results.

Finally, the primary analysis applies to participants who received the study drug and completed follow-up. Enrollment is listed as 3623, while 3131 are listed at risk for the serious adverse event outcome; the reason for the difference is not reported. The record does not explain missing-data handling or provide a detailed analysis plan. These limits define the scope of interpretation: the posted data describe a safety observation in a particular treated population, rather than a causal comparison or a complete account of every enrolled participant's outcomes.

14. Why This Trial Matters Statistically

Post-marketing surveillance addresses a different statistical question from a randomized efficacy trial. It records safety outcomes among people who used a treatment in the setting described by the registry. Such information can add to the description of events observed in practice, while requiring careful attention to the population definition, observation window, event definitions, and limits of causal interpretation.

This record makes the analysis population explicit: the Safety Set includes participants who received study drug and completed follow-up. The serious adverse event result is reported for 3131 at risk, while enrollment is listed as 3623. The reason for the difference is not reported in the registry record. That distinction matters because a result calculated in a defined follow-up population should not be casually generalized to everyone enrolled.

The endpoint also illustrates why event definitions matter. Serious adverse events include outcomes such as hospitalization and life-threatening experience, as well as death and other specified consequences. A safety summary must be interpreted using that definition rather than treating all adverse events as interchangeable. The record separately lists serious-event terms, which add descriptive detail without establishing causation.

Statistically, the registry specifies an exact-method 95% confidence interval, an appropriate kind of uncertainty summary for a binary outcome, but does not report its limits. This leaves the precision of the primary percentage difficult to judge. The lack of a like-for-like control group likewise means the observed safety experience cannot be interpreted as a comparative treatment effect. These are not defects that can be repaired by rephrasing the observed count; they are boundaries on what the design and recorded results can answer.

The record also lists multiple outcomes, while analysis entries, multiplicity procedures, and missing-data methods are not reported. Recognizing these omissions helps readers separate clearly recorded descriptive findings from questions that remain unresolved. The statistical value of the record lies in its defined safety observation and event reporting, interpreted with those constraints in view.

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 has no reported concurrent control group, and the record states that it is not a randomized comparison. This limits the ability to distinguish events associated with treatment from background events or events related to participants' health and other circumstances. Allocation is not stated, and the registry cautions that arms are not a like-for-like control comparison.

The primary result is based on the Safety Set, defined as participants who received study drug and completed follow-up. Enrollment is listed as 3623, compared with 3131 at risk for the serious adverse event outcome. The reason for this difference, details of follow-up completion, and handling of participants without complete follow-up are not reported in the registry record.

The record states that an exact-method 95% confidence interval was calculated, but its limits are not reported. Term-specific counts are also not reported, and displayed percentages may be rounded. The serious-event terms therefore cannot be independently assessed from counts in this record, and the displayed percentages should not be treated as causal estimates.

Although eight outcome measures are listed, registered analysis entries are not reported. The detailed statistical plan, multiplicity methods, interim analyses, sample-size justification, and missing-data procedures are not reported in the registry record. Numerical results for secondary glycaemic and effectiveness outcomes are not reported either. The record does not describe participant characteristics, site structure, treatment duration in practice, or procedures for determining event relatedness. These omissions restrict assessment of representativeness, analysis choices, and the precision and context of the findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study for Post-Marketing Surveillance of Nesina® Tablet Monotherapy or Combination Therapy in Participants With Type 2 Diabetes (T2DM) in South Korea — NCT04980040.
• Registry record last updated 2022-04-05; status last verified 2022-03.
• Results first posted 2022-04-05.
• 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

This completed post-marketing surveillance study concerns Nesina® tablet (alogliptin) use in participants with type 2 diabetes in South Korea. Takeda is listed as sponsor. The study start is 2014-04-19, primary completion is 2019-08-30, and enrollment is 3623.

The primary outcome is the percentage of participants with serious adverse events, assessed from first dose through 30 days after the last dose, up to 79.77 weeks. The Safety Set consists of participants who received study drug and completed follow-up. The registry lists 37 participants with serious adverse events among 3131 at risk and records 0 deaths. An exact-method 95% confidence interval is specified, but its limits are not reported in the registry record.

The record describes one Nesina® Tablet group and no randomized like-for-like control comparison. Eight outcome measures are listed, including safety and glycaemic measures; registered analysis entries are not reported. The detailed analysis plan, missing-data methods, and numerical secondary outcome results are not reported in the registry record. The findings are therefore descriptive safety information for the stated population and observation period.