Effect of DPP4 Inhibition on Growth Hormone Secretion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of DPP4 Inhibition on Growth Hormone Secretion (NCT01701973), a randomized phase 4 study. The primary outcome is Aim 1: Stimulated Peak Growth Hormone Level.

2. Clinical Question

The study's central biological hypothesis was that DPP4 inhibition would decrease degradation of growth hormone releasing hormone and thereby increase stimulated growth hormone secretion. The registry description also gives a second, related hypothesis: that reduced degradation of growth hormone releasing hormone during acute DPP4 inhibition would increase growth-hormone-mediated, endothelium-dependent vasodilation, independently of GLP1.

These are related but distinct questions. Aim 1 concerns a hormone response after arginine stimulation; Aim 2 concerns vascular response and includes additional pretreatments intended to examine possible mechanisms. The primary outcome listed in the record belongs to Aim 1. The record does not report a numerical result for the primary outcome or a single comparison that resolves its multiple measurement times.

3. Trial Design

The record describes a completed Phase 4 study with randomized allocation, double masking, and a crossover model. Enrollment is listed as 44. Rather than assigning each participant to only one treatment, the Aim 1 description says subjects underwent two study days: sitagliptin on one day and placebo on another, with the order randomized and blinded. A washout period separated the days, but its duration and other details are not reported in the registry record.

The primary-outcome population is described as subjects who completed both Aim 1 study days. They were young, healthy adults without chronic medical conditions and were not taking medications; oral birth control use was not permitted. The number who completed both days is not reported in the registry record. The group descriptions each list 14 healthy subjects, while the overall enrollment is listed as 44. The record does not explain how these figures relate to the analyzed population.

The record also describes three groups for Aim 2. Each group receives sitagliptin and is randomized, in a double-blind crossover fashion, to pretreatment with one active agent versus placebo. The listed agents are L-NMMA, pegvisomant, and Exendin 9-39. This structure is intended to examine different possible pathways in the vascular response; the record does not report a single combined Aim 2 comparison.

Arginine was given intravenously to stimulate growth hormone secretion, and growth hormone levels were assessed over the following three hours. The exact sequence and timing of all Aim 2 procedures, the washout duration, and the detailed allocation procedures are not reported in the registry record. The listed start and primary completion dates are 2013-01 and 2017-05, respectively. The study status is completed.

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: In Aim 1, Healthy adults were randomized in a double-blinded cross-over fashion to sitagliptin vs placebo. A minimum 8 week wash-out separated Aims 1 \& 2. 23 of the same adults who completed Aim 1 participated in Aim 2. In Aim 2, these adults were divided into three subgroups and randomized to sitagliptin+placebo vs. sitagliptin+antagonist.

Only the first 6 of 8 groups are shown.

Aim 1: First Intervention (1 Day)

Reasons for not completing this period:

Aim 1: Second Intervention (1 Day)

Aim 2: First Intervention (1 Day)

Aim 2: Second Intervention (1 Day)

Analysis population for the primary outcome, as defined in the registry: Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.

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.

6. Primary Endpoint

The registry lists the primary outcome as Aim 1: Stimulated Peak Growth Hormone Level, measured over Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.

The primary endpoint is titled “Aim 1: Stimulated Peak Growth Hormone Level.” It measures growth hormone concentration in ng/ml after secretion is stimulated with arginine. The record describes an arginine infusion of 30 grams i.v. over 30 minutes, followed by growth hormone assessments at 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, and 180 minutes. The 30-minute assessment is described as the completion of the infusion.

Growth hormone is the biological response of interest because the study hypothesis proposes that DPP4 inhibition may reduce degradation of growth hormone releasing hormone and increase stimulated growth hormone secretion. Measuring the response after a stimulus is intended to assess secretion under a defined challenge rather than relying only on an unstimulated level. This is a general description of why a stimulated hormone measure can be informative; it does not establish that the proposed effect occurred.

The outcome's statistical form is a mean with standard deviation. The record lists several measurement times but does not identify a single time point as the sole numerical comparison or report a numerical summary of the endpoint. It also does not describe how the measurements across time were combined to define a peak for analysis. Consequently, the endpoint's clinical and biological purpose can be described, but its observed magnitude and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, double-blind, and crossover. Randomization is a way to assign treatment order by chance; in a crossover study, the order of conditions can influence what participants experience first. Double masking is intended to keep participants and relevant study personnel unaware of the assigned condition, reducing the opportunity for expectations to affect care or measurement. These are general purposes of the design labels. The registry record does not report the detailed randomization procedure or which roles were masked.

What does a crossover comparison use?

In a crossover design, the same participant receives more than one condition at different times. The Aim 1 description says participants had a sitagliptin study day and a placebo study day, with a washout period between them. In general, the statistical comparison can use the within-participant difference between conditions. This can help separate a treatment contrast from stable person-to-person differences. It does not remove all sources of bias: time trends, treatment order, carryover, and changes between study days may still matter.

A washout period is intended to reduce the influence of a prior condition on a later condition. Its adequacy depends on the intervention and outcome, as well as the duration and timing of measurement. The duration of the washout and any assessment of carryover are not reported in the registry record. Nor does the record state whether the statistical analysis included period or sequence effects. Those omissions prevent a detailed appraisal of the crossover analysis.

What do the mean and standard deviation describe?

The endpoint is a continuous measure, and its parameter is listed as a mean with standard deviation. In general, a mean describes the central level of the measured values. A standard deviation describes the spread of individual measurements around that mean; it is not the same as a confidence interval, which describes uncertainty in an estimate. The registry record gives the outcome's unit as ng/ml but does not report the means or standard deviations at the assessment times.

Growth hormone was assessed repeatedly after arginine stimulation. Repeated observations on the same participant are generally correlated rather than independent. A suitable analysis may need to account for that within-person correlation, but the registry record does not identify a statistical model, a summary rule for the peak, or a method for analyzing the time course. It therefore cannot be assumed that a particular repeated-measures approach was used.

Why do multiple times matter?

When an outcome is assessed at several times, each time can produce a separate contrast. If multiple contrasts are tested, the chance of a false-positive finding across the set can increase unless the analysis plan accounts for multiplicity. Alternatively, investigators can define a single summary or primary time point in advance. The registry record lists the times and says the primary outcome has several categories or time points, but it does not report a single reduced comparison, an analysis hierarchy, or a multiplicity procedure. This is a general statistical concern, not evidence that a particular error occurred.

What can the planning assumptions tell readers?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of finding an effect. They depend on the effect used as a reference and on the stated assumptions. The numerical planning results are not reported in the registry record, and the record does not report the trial's own sample-size justification. The crossover design described for the primary aim also differs from the equal-allocation, two-arm framing of the planning assumptions, so the assumptions should not be read as a description of the actual analysis.

In general, a prospective sample-size calculation uses a target effect, a variability assumption, an error threshold, and a desired power to estimate a planning requirement. It does not show whether the completed study found an effect. When an observed effect is used to illustrate a later study, the result is particularly dependent on the observed estimate and its uncertainty. No numerical effect estimate or uncertainty interval for the primary outcome is reported in the registry record, limiting interpretation of such planning illustrations.

What statistical details remain unknown?

The registry record does not report the analysis model, treatment-effect estimate, confidence interval, p-value, handling of missing measurements, or the assumptions used for the primary analysis. It also does not report whether the analysis was adjusted for any covariates, how outliers were handled, or whether analyses were conducted according to a prespecified plan. These are not details that can be inferred from the study's randomized, double-blind crossover designation.

For a crossover analysis, the number of participants contributing paired data and the completeness of measurements at each time are important. The record says that data from subjects completing both Aim 1 study days were analyzed but does not give that number or describe participants who did not complete both days. It also does not say whether partial measurements were retained or excluded. Without these details, readers cannot assess the analysis population or determine how missing data might affect the estimate.

Finally, the record lists eight outcome measures and identifies secondary outcomes relating to tissue plasminogen activator activity and growth hormone levels. The presence of multiple outcomes can complicate interpretation if many results are tested. The registry record does not report an adjustment strategy or distinguish confirmatory from exploratory analyses. No claim about multiplicity control or the statistical method used is justified by the information recorded.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is assessed at several time points after arginine stimulation. The registry record says this outcome was not reduced to one comparison and lists eight outcome measures overall. It also lists secondary outcomes involving tissue plasminogen activator activity and growth hormone levels. When multiple outcomes or time points are examined, a prespecified hierarchy or multiplicity adjustment can help clarify which comparisons are confirmatory and how to interpret chance findings. The registry record does not report such a hierarchy or adjustment, so the handling of multiplicity is not reported in the registry record.

The primary-outcome description states that data from all subjects who completed both Aim 1 study days were analyzed. The number of completers is not reported in the registry record. It does not describe withdrawals, incomplete study days, missing measurements at particular times, or the method used to handle missing data. It is therefore not possible to tell whether analysis included only complete paired observations, whether partial records were used, or whether any imputation or sensitivity analysis was performed.

The record does not report a detailed analysis population definition beyond completion of both Aim 1 study days. It does not state whether the analysis followed an intention-to-treat principle, how protocol deviations were handled, or how the Aim 2 populations were defined for analysis. It also does not report a statistical analysis plan or interim analyses. These methods are not inferable from the randomized and double-blind design.

These reporting gaps limit evaluation of the result, but they do not establish that the study failed to address multiplicity or missing data in its conduct. They indicate that those methods are not reported in the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists serious adverse events, other adverse events, and deaths by exposure group. Serious adverse events are listed as 0 in every group, and deaths are listed as 0 in every group. The recorded numbers at risk are 40 for Sitagliptin, 43 for Placebo, 5 for Sitagliptin Plus Pegvisomant, 9 for Sitagliptin Plus LNMMA, and 8 for Sitagliptin Plus Exendin 9-39. These denominators differ and should be read within their recorded groups rather than combined.

Other adverse events are listed for 7 in Sitagliptin, 1 in Placebo, 2 in Sitagliptin Plus Pegvisomant, and 0 in each of Sitagliptin Plus LNMMA and Sitagliptin Plus Exendin 9-39. The record does not provide the event terms in the listed serious-event summary, nor does it report the nature, timing, severity, or attribution of the other events. The counts therefore do not show whether an event was caused by treatment.

These figures are descriptive, not a formal comparison of safety. In a crossover study, exposure groups may reflect treatment periods rather than independent sets of participants. The differing denominators and the absence of event-level details make direct comparisons especially limited. Zero recorded serious events or deaths in these groups should not be interpreted as proof that risk is absent.

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

This study is framed as a mechanistic investigation of acute DPP4 inhibition, stimulated growth hormone secretion, and vascular responses. Its primary outcome is a stimulated growth hormone measure in healthy lean adults, not a clinical outcome in people being treated for obesity, pre-diabetes, or diabetes. The registry description's population restrictions and crossover procedures define the setting in which the question was studied.

The record's biological hypotheses are proposals to be tested, not findings. It describes the expectation that sitagliptin could increase stimulated growth hormone secretion by decreasing degradation of growth hormone releasing hormone. It also describes a hypothesis about growth-hormone-mediated vasodilation and separate mechanistic pretreatments. The record does not provide a numerical primary result or a single comparison that permits those hypotheses to be judged from the posted information.

Even if a numerical change in growth hormone were reported, interpreting that change would require its size, uncertainty, and analysis context. A statistically detectable difference is not automatically important in practice, and an imprecise estimate may be compatible with multiple possibilities. Here, the registry record does not report the primary treatment estimate, its confidence interval, or its p-value. The magnitude and precision of the primary effect therefore cannot be described.

The scope is also limited by the studied population and acute study conditions. The record describes healthy lean adults and two study days with sitagliptin or placebo, not chronic treatment in people with obesity or pre-diabetes. The brief summary itself notes that a further study may evaluate chronic DPP4 inhibitor therapy in a population with obesity and pre-diabetes. The findings of this trial, as described in the record, cannot be generalized to that different population or treatment duration.

Accordingly, the registry record establishes the research question and design, but it does not establish that sitagliptin increased or did not increase growth hormone, nor that it changed vasodilation. It also does not support a conclusion about long-term clinical benefit or harm. Those conclusions would require results and analyses not reported in the registry record.

13. Why This Trial Matters Statistically

The trial raises a statistical issue common to mechanistic studies: a clearly specified biological hypothesis can still be difficult to evaluate when the outcome is measured repeatedly and the analysis is not reported as one interpretable comparison. Growth hormone was measured at several times after stimulation, while the primary outcome is described as a peak. The rule used to define or analyze that peak matters because it determines which observations contribute to the estimate and how uncertainty is quantified.

The crossover design is also statistically relevant. Each participant contributes measurements under both sitagliptin and placebo, so a within-participant comparison can remove some stable variation between people. At the same time, period effects, treatment order, carryover, and incomplete pairs can affect interpretation. The registry record gives the broad design but not the analysis model or its handling of these issues. This illustrates why design labels alone are not enough to evaluate an estimate.

The study also connects a hormone endpoint with a proposed vascular mechanism and lists additional pretreatments for that aim. Such mechanistic structures can generate multiple outcomes and comparisons. Without a reported analysis hierarchy or multiplicity approach, it is difficult to distinguish a primary confirmatory result from other possible findings. The record lists the outcomes but does not provide the needed statistical detail.

Finally, the registry record makes clear that outcome definition and outcome evidence are different. It specifies what the investigators intended to measure, yet gives no numerical primary comparison. Readers can identify the estimand of interest in broad terms, but cannot assess its size or precision. That gap is important in evidence synthesis: a study's design and hypothesis may be informative, while a quantitative treatment-effect contribution requires an estimate and uncertainty measure.

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 primary limitation for interpreting the main question is that the registry record does not report a single numerical primary-outcome comparison. It provides no mean or standard deviation values for the listed assessment times, and no treatment-effect estimate, confidence interval, or p-value. It therefore does not allow an assessment of the direction, magnitude, or precision of the primary result.

The endpoint spans multiple measurement times, but the record does not explain how those times were combined or how a peak was defined for analysis. It does not report the statistical model, multiplicity handling, or whether time-specific comparisons were prespecified. This limits evaluation of how the stated primary outcome was translated into an inferential analysis.

The record states that subjects completing both Aim 1 study days were analyzed, but it does not report the number analyzed, the number with incomplete visits, or the handling of missing observations. The washout duration and any assessment of period or carryover effects are also not reported in the registry record. These omissions matter for assessing a crossover study's analysis and the robustness of its comparisons.

The record lists overall enrollment as 44 and describes three groups, each with 14 healthy subjects, but does not explain how those figures correspond to the actual analyzed populations. It also does not report detailed statistical methods for Aim 2 or numerical outcomes for its mechanistic comparisons. The adverse-event record gives group counts but not event descriptions, timing, or attribution.

Finally, the described population is healthy and lean, and the primary comparison concerns acute study days. The record does not provide evidence about chronic therapy or populations with obesity and pre-diabetes. The registry's stated possibility of further study in that population is not a result of this trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of DPP4 Inhibition on Growth Hormone Secretion — NCT01701973.
• Registry record last updated 2018-05-29; status last verified 2018-05.
• Results first posted 2018-05-29.
• 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 record describes a completed Phase 4 randomized, double-blind crossover study sponsored by Vanderbilt University. Enrollment is listed as 44, and the listed dates are a start in 2013-01 and primary completion in 2017-05.

The primary outcome is stimulated peak growth hormone level after arginine infusion, measured at several times and summarized in the record as a mean with standard deviation. Aim 1 compares sitagliptin with placebo across study days. Aim 2 describes separate pretreatments with L-NMMA, pegvisomant, or Exendin 9-39 alongside sitagliptin and placebo.

The registry record reports no analyses and does not reduce the multi-time-point primary outcome to one numerical comparison. It also does not report an effect estimate or its uncertainty. Serious adverse events and deaths are listed as 0 across the recorded groups; other adverse-event counts vary by group. The record does not provide event descriptions or attribution.