A 12-WEEK TITRATE STUDY TO EVALUATE SAFETY, TOLERABILITY AND PHARMACODYNAMICS OF PF-06882961 IN ADULTS WITH TYPE 2 DIABETES MELLITUS AND IN NON-DIABETIC ADULTS WITH OBESITY: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A 12-WEEK TITRATE STUDY TO EVALUATE SAFETY, TOLERABILITY AND PHARMACODYNAMICS OF PF-06882961 IN ADULTS WITH TYPE 2 DIABETES MELLITUS AND IN NON-DIABETIC ADULTS WITH OBESITY (NCT04617275), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity.

2. Clinical Question

This is a safety and pharmacodynamic study, not a registry record of a single efficacy comparison. Its groups include several PF-06882961 titration schedules in participants with type 2 diabetes, a PF-06882961 group in non-diabetic adults with obesity, and placebo groups in both populations. Those differences matter for interpretation: counts from different populations and titration schedules should not be treated as though they came from interchangeable groups.

The primary endpoint concerns treatment-emergent adverse events (TEAEs). An event qualified if it arose after the first dose or worsened after treatment began, and events were followed through the follow-up visit. The registry also lists secondary outcomes that include laboratory, vital-sign, electrocardiogram, mental-health, and fasting-plasma-glucose measures. The displayed primary outcome is a safety count, not a measure of change in diabetes or obesity.

The registry record does not report a single pooled comparison or an effect estimate for the primary outcome. It lists counts of participants with serious and other adverse events by group. These counts can describe what was recorded in each arm, but by themselves they do not establish that one titration strategy caused more or fewer events than another.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group Phase 2a study with placebo control. The official title also describes the study as sponsor-open. The study evaluated PF-06882961 titration over 12 weeks in adults with type 2 diabetes treated with metformin and in non-diabetic adults with obesity. The registry lists Pfizer as the sponsor and reports that the study is completed.

There were multiple active-treatment groups rather than one uniform PF-06882961 regimen. In the type 2 diabetes population, listed target doses were 80 mg, 120 mg, and 200 mg twice daily, with different starting doses and titration schedules. A 200 mg twice-daily group is also listed for non-diabetic adults with obesity. Placebo was taken twice daily in separate type 2 diabetes and non-diabetic obesity groups. These design features mean that the active groups represent different titration regimens and, in one case, a different study population.

The registry reports enrollment of 151. The safety analysis set is defined as participants who were randomly assigned to study treatment and took at least 1 dose of investigational product. The adverse-event results list the number at risk in each group, which is the denominator associated with each group’s reported counts. The registry record does not report the allocation ratio or the number assigned to each group before the safety-set restriction.

The primary safety outcome covers baseline through follow-up on Day 112. The record describes mild, moderate, and severe intensity categories and says investigators used clinical judgment when assessing whether events were related to study treatment. It does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. The record lists 30 outcome measures and 96 analyses, but those totals do not specify which comparisons or analytic decisions were prespecified.

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: A total of 370 participants were screened for eligibility, of which 151 participants (123 in the type 2 diabetes mellitus \[T2DM\] arms and 28 in the non-diabetic obesity arms) were randomized to receive the danuglipron or placebo in one of the 8 treatment arms.

Only the first 6 of 8 groups are shown.

Treatment Period

Reasons for not completing this period:

Follow-up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants randomly assigned to study treatment and who took at least 1 dose of investigational products (IP).

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: A total of 151 participants were assigned to the treatment and treated with danuglipron or placebo.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity, measured over Baseline through follow-up (Day 112).

The primary endpoint is the number of participants with treatment-emergent adverse events by severity, from baseline through follow-up on Day 112. A treatment-emergent event was one that was absent before treatment and occurred between the first dose and follow-up, or one that worsened after treatment began. The endpoint counts participants with events; it is not a count of every event occurrence.

The registry defines event intensity as mild, moderate, or severe. Mild events were described as easily tolerated, causing minimal discomfort, and not interfering with daily activities. Moderate events caused sufficient discomfort and interfered with normal daily activities. Severe events prevented normal daily activities. Investigators used clinical judgment to assess the potential relationship between an event and the investigational product.

TEAE counts are used in safety assessment because they capture medical occurrences arising or worsening after treatment starts, whether or not the investigator considers them treatment-related. Including events without requiring a judgment of causation helps describe the safety experience during exposure. Severity categories add information about intensity, but counts alone do not describe duration, recurrence, or the full clinical context of an event.

The registry’s posted group-level results report counts for serious adverse events and other adverse events. They do not provide the mild, moderate, and severe participant counts for the primary endpoint. Consequently, the available counts should not be read as a complete severity breakdown of that endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants who experienced a treatment-emergent adverse event, rather than a count of all event episodes. One participant may have had more than one event, but the participant count records that person once within the relevant outcome category. This distinction matters: a count of affected participants does not reveal how many total events occurred or whether events recurred.

For the safety results, each group has a number at risk and a number affected. The denominator identifies how many participants contributed to that group’s safety results; the numerator is the count of participants with the specified event category. The registry record gives these counts but does not provide confidence intervals or a formal test for differences between groups. No percentages are needed to describe the reported results, and no additional comparative estimates should be inferred from the counts alone.

What is the role of the safety analysis set?

The record defines the safety analysis set as all participants randomly assigned to study treatment who took at least 1 dose of investigational products. This definition focuses safety assessment on participants with treatment exposure. It is not identical, by definition, to an analysis of every randomized participant, because the safety set requires at least 1 dose. The registry record does not report a separate analysis of all randomized participants for this endpoint, nor does it give reasons for any differences between randomized and safety populations.

In general, analysis populations determine which participants contribute to a result. Safety analyses commonly use an exposed population because adverse events are assessed in relation to treatment exposure. That choice does not, on its own, resolve how missing follow-up or incomplete event reporting was handled. Those procedures are not reported in the registry record.

Why does group structure matter?

The study has several active-treatment groups with differing titration schedules and target doses, as well as placebo groups in two populations. The active schedules are therefore not simply repeated copies of one treatment. Comparisons across groups may also mix differences in dose escalation with differences in participant population. For instance, the registry lists a non-diabetic obesity group separately from the type 2 diabetes groups. A raw contrast between those groups could not isolate a treatment effect from population differences.

Randomization helps balance measured and unmeasured characteristics across groups on average when comparing randomized arms according to an appropriate analysis. It does not make every group identical, guarantee balance in a small group, or remove the need to account for the actual design and analysis plan. The registry record does not report the allocation ratio, the randomization method, or an adjusted statistical comparison for the adverse-event outcome.

How should uncertainty be considered?

A confidence interval is a statistical range that expresses uncertainty around an estimated quantity under a specified analysis. In general, an interval around an event-risk estimate can help readers distinguish a relatively precise estimate from one with substantial uncertainty. No confidence intervals for the adverse-event results are reported in the registry record, so the precision of between-group differences cannot be assessed from those counts alone.

Small group counts can be especially uncertain. A count of zero serious events is an observation for the participants followed in that group; it is not an estimate of zero risk in all future participants. In general, absence of observed events in a study does not rule out events that are uncommon or that may occur with longer exposure. The record’s follow-up window ends at follow-up on Day 112, so the results describe the period specified for this endpoint rather than longer-term experience.

What do the design and sample-size assumptions tell us?

The record identifies a Phase 2a, randomized, double-blind, parallel-group, placebo-controlled design. It does not report the trial’s own sample-size justification. The sample-size assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such illustrations are planning aids based on assumptions; they are not observed power and do not show that the study was designed to detect a particular difference. The record does not reduce the primary outcome to one comparison, so a single effect-based calculation should not be interpreted as a definitive design assessment of the primary safety question.

In general, planning estimates depend on the outcome, the effect one wants to detect, and assumptions about variability or event frequency. If those assumptions differ from what is observed, the planning illustration may not describe the study’s actual operating characteristics. The registry record does not report the design inputs or justification used by the sponsor, so the planning assumptions should not be mistaken for the original protocol’s rationale.

Why are multiple outcomes and analyses relevant?

The registry lists 30 outcome measures and 96 analyses. When many outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can increase. Statistical approaches for handling multiplicity can be prespecified, but the registry record does not report whether an adjustment was planned or applied. The number of listed analyses alone does not reveal which results were confirmatory, exploratory, adjusted, or selected for reporting.

For the safety endpoint, the main limitation is not a lack of an appropriate general concept: participant counts are a direct descriptive way to report whether events occurred. The limitation is that the posted data do not include severity-specific counts, uncertainty estimates, or a reported comparative analysis. Statistical significance, clinical importance, and the completeness of safety follow-up are separate questions, and the counts alone cannot answer all of them.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures and 96 analyses. This indicates that the record contains multiple outcomes and analyses, but it does not establish which analyses were primary, which were prespecified, or whether any multiplicity procedure was used. The primary endpoint itself is described as a count of participants with TEAEs by severity, while the available group-level counts are separated into serious and other adverse events. Severity-specific results are not reported in the registry record.

Multiplicity matters in general because testing or examining many outcomes can increase the chance of apparently unusual findings arising by chance. Prespecified strategies can address that issue, but the record does not report a multiplicity adjustment or an analysis hierarchy for the listed outcomes. The listed number of analyses is not sufficient to infer that every result was tested independently or to determine the appropriate adjustment.

The safety population is defined as randomized participants who took at least 1 dose of investigational product. The record does not report how missing adverse-event information, missed visits, withdrawal, or incomplete follow-up was handled. It also does not report a separate analysis population for the primary endpoint beyond the stated safety set. Without those details, it is not possible to assess whether missingness could have affected the reported counts.

The statistical analysis plan, interim-analysis procedures, and the sponsor’s sample-size justification are not reported in the registry record. The planning illustration assumptions are not a substitute for those details. As a result, the available information supports describing the reported counts, but not reconstructing the full inferential strategy or determining how all outcomes and missing data were handled.

11. 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 non-serious adverse event terms

For each listed group, the serious adverse-event count is 0, and the death count is 0. The other adverse-event counts are 8 of 16 for placebo in type 2 diabetes, 4 of 6 for placebo in non-diabetic obesity, 11 of 20 for PF-06882961 80 mg BID Low, Slow in type 2 diabetes, and 13 of 22 for 80 mg BID High, Slow in type 2 diabetes. The counts are 14 of 22 for each 120 mg BID type 2 diabetes group, 14 of 21 for 200 mg BID in type 2 diabetes, and 18 of 22 for 200 mg BID in non-diabetic obesity.

These figures describe the number of participants in each group who were recorded in the serious or other adverse-event category during the specified safety period. The serious-event count is not a severity rating, and the other-event count does not show the mild, moderate, or severe breakdown. The endpoint description and the posted adverse-event categories therefore answer related but not identical questions.

Group counts should be read with their denominators and population labels. They are descriptive observations, not adjusted risk estimates or evidence of a causal difference between regimens. The registry record does not provide confidence intervals, a statistical comparison, or further event-level detail for these counts.

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

The posted safety data establish that the registry records zero serious adverse events and zero deaths in each listed group during the endpoint period. They also show that participants with other adverse events were recorded in every group. The counts vary across groups, but group sizes, participant populations, and titration schedules also vary. The registry does not report a formal comparison that would support ranking those groups by safety.

The counts do not show that PF-06882961 caused or prevented any particular event. The endpoint includes events whether or not investigators considered them related to treatment, and the record does not provide the relationship assessment for each event. The event counts also do not establish the intensity, duration, recurrence, or consequences of the other adverse events. Although the primary outcome is described by severity, severity-specific participant counts are not reported in the registry record.

These results also do not answer the pharmacodynamic or glucose questions. The registry lists fasting plasma glucose change outcomes at Week 2, Week 4, and Week 6, but numerical results for those outcomes are not reported in the information. The adverse-event counts cannot be used as a substitute for those measures.

In general, a trial’s observations apply to the participants and follow-up represented in its results. This study was conducted in adults with type 2 diabetes treated with metformin and non-diabetic adults with obesity, with follow-up through Day 112 for the primary safety endpoint. The registry record does not report longer-term safety results. Its reported counts should therefore be understood as descriptive observations for the listed groups and period, not as a complete account of risks in other populations or over longer periods.

Because there are no reported uncertainty intervals or comparative analyses, the data do not quantify how precisely the event experience differs between groups. A zero count in a study group is not proof that an event is impossible, and an observed count in a group does not by itself show that treatment caused the event. The registry record supports careful description, not a conclusion about treatment benefit or harm.

13. Why This Trial Matters Statistically

This study illustrates why safety results need both clear outcome definitions and careful attention to the populations being compared. A treatment-emergent adverse event is defined by its timing relative to treatment, while an investigator’s judgment about treatment relationship is a separate assessment. Reporting counts regardless of relationship can give a broad account of events during treatment, but it does not establish causation.

The trial’s several titration schedules also make the analysis more complex than a simple contrast between one active regimen and placebo. Starting doses, target doses, escalation schedules, and study populations differ across groups. Descriptive counts can be useful, but readers need a prespecified comparative analysis to determine whether observed differences are larger than might arise from variation in group size or chance.

The registry’s primary endpoint is defined by severity, yet the posted results are presented as serious and other adverse-event counts. Recognizing that these classifications are not interchangeable prevents readers from treating a zero serious-event count as a complete report of mild, moderate, or severe TEAEs. It also highlights the importance of reporting outcome data in the categories named by the endpoint.

Finally, the record lists many outcome measures and analyses without reporting a multiplicity strategy, missing-data procedures, or the statistical analysis plan. Those omissions limit what can be inferred from the posted counts. This is a useful example of the difference between a descriptive safety summary and a fully documented statistical comparison: the former reports what was observed, while the latter also explains the analysis, uncertainty, and scope of the conclusions.

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.

Several limitations are specific to the information reported for this study. The primary outcome is TEAEs by severity, but the available group results do not give participant counts separately for mild, moderate, and severe events. Instead, the registry lists serious and other adverse-event counts. Since seriousness and intensity are different classifications, the posted numbers do not fully resolve the primary endpoint as described.

The groups are not uniform in population or titration regimen. The registry includes adults with type 2 diabetes treated with metformin and non-diabetic adults with obesity, and multiple starting doses and target doses. The placebo groups are also population-specific. This structure makes unadjusted comparisons across all groups difficult to interpret, particularly when they combine different populations and regimens.

The registry does not report confidence intervals, formal statistical comparisons, event-level descriptions, or the number of events per participant. It therefore does not show the precision of differences between groups, the types of events making up the other-event counts, or whether participants experienced repeated events. The absence of serious adverse events in the listed groups is descriptive and does not establish the absence of serious risk.

The record does not report how missing data or incomplete follow-up were handled, whether there was an interim analysis, the statistical analysis plan, or the sponsor’s sample-size justification. It lists numerous outcome measures and analyses without describing a multiplicity strategy. These gaps prevent a full assessment of the inferential methods and the risk that selective reporting or missing information could influence interpretation. Follow-up for the primary endpoint is specified through Day 112, and longer-term outcomes are not reported in this record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A 12-WEEK TITRATE STUDY TO EVALUATE SAFETY, TOLERABILITY AND PHARMACODYNAMICS OF PF-06882961 IN ADULTS WITH TYPE 2 DIABETES MELLITUS AND IN NON-DIABETIC ADULTS WITH OBESITY — NCT04617275.
• Registry record last updated 2022-12-08; status last verified 2022-11.
• Results first posted 2022-12-08.
• 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.

18. Record Summary

The registry describes a completed, randomized, double-blind, sponsor-open, parallel-group Phase 2a, placebo-controlled study of PF-06882961 titration over 12 weeks. It enrolled 151 adults with type 2 diabetes treated with metformin and non-diabetic adults with obesity. Treatment groups used different twice-daily titration schedules, and placebo groups were listed for both populations.

The primary endpoint was the number of participants with TEAEs by severity from baseline through follow-up on Day 112. The safety analysis set included randomized participants who took at least 1 dose. Posted group results report zero serious adverse events and zero deaths in each group, alongside counts of participants with other adverse events. Severity-specific counts, confidence intervals, and a formal comparison are not reported in the registry record.

The record lists 30 outcome measures and 96 analyses. It does not report the multiplicity approach, missing-data procedures, interim analyses, statistical analysis plan, or the trial’s sample-size justification. The results therefore support a descriptive account of the listed adverse-event counts, but not a precise comparative conclusion about safety or a full assessment of the study’s inferential methods.