Research Study Looking at How Well Semaglutide Works in People Suffering From Obesity and Knee Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Research Study Looking at How Well Semaglutide Works in People Suffering From Obesity and Knee Osteoarthritis (NCT05064735), a randomized phase 3 study. The primary outcome is Percentage Change in Body Weight.

2. Clinical Question

The trial also considered knee-related pain and daily life in its summary, with secondary outcomes covering physical function, stiffness, total WOMAC score, bodily pain, waist circumference, and body-weight reduction thresholds. The posted secondary results provide additional context, but the primary question is the comparison of mean body-weight change.

3. Trial Design

This was a completed phase 3, randomized, triple-masked, parallel-group trial sponsored by Novo Nordisk A/S. The registry records enrollment of 407. The study started on 2021-10-01, and primary completion was recorded as 2023-07-24. The treatment comparison was semaglutide 2.4 mg once weekly versus placebo, with both groups also receiving a reduced-calorie diet and increased physical activity.

The registry summary describes weekly injections and approximately 1 ½ years of study participation, with 14 clinic visits. It describes discussions with study staff about healthy eating and physical activity. The primary endpoint timeframe was baseline (week 0) to end of treatment (week 68). The primary outcome description defines the in-trial period as the uninterrupted interval from randomization to the date of last contact with the trial site.

The reported number analyzed differs by outcome. For the primary body-weight endpoint, the record lists 253 participants in the semaglutide group and 120 in the placebo group with available data. Those analyzed numbers are not a replacement for the registry’s enrollment figure: the record’s endpoint definition specifically describes the analyzed group as participants with available outcome data.

The summary lists eligibility restrictions, including exclusion of people with diabetes and people who had knee joint replacement surgery. It also describes a restriction on pain medication before 6 clinic visits and pregnancy-related exclusions for women. These details help characterize the enrolled population and visit requirements, but the full eligibility criteria and the trial’s original sample-size justification are not reported in the registry record.

Triple masking indicates that the registry classifies the trial as masked at three levels, but the identities of those masked are not reported in the registry record. The allocation concealment details, the specific randomization procedure, and the original statistical analysis plan 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: The study included a screening visit followed by visits every 4th week during dose escalation period and every 8th week until end-of-treatment (week 68). Follow-up period was 7 weeks after end-of-treatment (week 75).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.

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: Full analysis set (FAS) included all randomized participants according to the intention-to-treat principle.

6. Primary Endpoint

The registry lists the primary outcome as Percentage Change in Body Weight, measured over Baseline (week 0), end of treatment (week 68).

The primary endpoint is percentage change in body weight from baseline (week 0) to the end of treatment (week 68), summarized as a mean. It expresses change relative to each participant’s baseline weight rather than a change in weight units. The registry defines the outcome as measured during the in-trial period, from randomization through the last contact with the trial site.

Body weight is a continuous measure, so the mean summarizes the central tendency of participants’ observed changes. The standard deviation describes how spread out individual changes were around each group mean; it is not the uncertainty in the mean difference. The registry identifies the full analysis set using the intention-to-treat principle and clarifies that the analyzed number for this endpoint is the number with available data.

A body-weight endpoint provides a direct quantitative comparison between randomized groups over the specified treatment period. The study summary also connects weight and knee symptoms as subjects of interest, but the primary endpoint itself is body-weight change, not pain or physical function. The secondary outcomes address some of those other domains. Their role is supplementary to the primary endpoint, and their interpretation depends on the measures and analyses reported for each outcome.

Percentage change is an average outcome, not a statement that every participant changed by the group mean. Group means do not describe the full distribution of individual responses. The registry record does not report an individual-response analysis for this endpoint.

7. Results Posted in the Registry

• Semaglutide 2.4 mg: mean -14.20 versus -2.50 on control; difference -11.70 (95% CI -13.16 to -10.24), standardized effect d = -1.51; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in WOMAC Physical Function Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Semaglutide 2.4 mg: mean -43.40 versus -25.80 on control; difference -17.60 (95% CI -23.15 to -12.05), standardized effect d = -0.69; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Semaglutide 2.4 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Short Form 36 (SF-36) Physical Functioning Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Semaglutide 2.4 mg: mean 12.70 versus 6.40 on control; difference 6.30 (95% CI 4.12 to 8.48), standardized effect d = 0.64; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Semaglutide 2.4 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Waist Circumference

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Semaglutide 2.4 mg: mean -13.30 versus -5.90 on control; difference -7.40 (95% CI -9.59 to -5.21), standardized effect d = -0.77; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Semaglutide 2.4 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the trial’s measurement beyond body-weight change. They include categorical body-weight reduction thresholds, WOMAC measures of physical function, stiffness and total score, SF-36 physical functioning and bodily pain, and waist circumference. The posted continuous secondary results generally show group contrasts in the direction of greater change in the semaglutide group. This pattern provides context alongside the primary body-weight result, but it does not establish that every secondary outcome has the same evidential strength or interpretation.

Some secondary outcomes are continuous measures and are summarized using means and standard deviations; others are categorical thresholds. These outcome types answer different questions. A mean change describes an average shift, whereas a threshold outcome concerns whether participants met a defined category. The registry’s secondary outcome listings do not make them interchangeable with the primary endpoint.

The registry record reports many outcome measures and does not report a multiplicity adjustment for the secondary comparisons. When several outcomes are examined, the chance of obtaining one or more apparently notable results by chance can increase. This is general statistical context. Without a reported adjustment strategy or a clear hierarchy of confirmatory secondary hypotheses, unadjusted secondary p-values carry less weight than the prespecified primary result.

The secondary findings can be viewed as supportive descriptive evidence about related domains, but their interpretation should account for the number of outcomes, the differing measurement scales, and the absence of reported multiplicity procedures. The registry record does not report a combined analysis that would establish an overall effect across the different secondary measures. The secondary pattern should therefore be considered alongside, rather than in place of, the primary endpoint and its reported ANCOVA analysis.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No)
• Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No)
• Change in WOMAC Physical Function Score
• Change in Short Form 36 (SF-36) Physical Functioning Score
• Change in Waist Circumference
• Change in WOMAC Stiffness Score
• Change in WOMAC Total Score
• Change in SF-36 Bodily Pain Score

9. Statistical Interpretation

10. Statistical Methods Explained

The primary result is reported in two forms: group means with standard deviations, and a sponsor analysis using ANCOVA. The re-calculated comparison is an unadjusted comparison of the posted summary statistics. The registry’s reported ANCOVA result is the sponsor’s analysis. These methods can yield different estimates because one is a direct comparison of group summaries and the other is a model-based estimate. The registry record does not report the full ANCOVA specification, so the precise reason for the numerical difference is not established by the posted details.

What does a mean difference describe?

For a continuous outcome, a mean difference compares the average outcome in one group with the average in the comparator group. The sign depends on the order of subtraction. In the reported primary comparison, the estimate is negative with semaglutide contrasted against placebo, consistent with the posted group means of -14.2 and -2.5. This is a group-level summary and does not imply that each participant had the same change.

The standard deviation shown with each group mean describes variation among participant outcomes. A larger standard deviation indicates more spread in the observed values around that group’s mean. It should not be read as the confidence interval for the mean or as a direct measure of the uncertainty in the contrast.

What does ANCOVA contribute?

ANCOVA is a model-based method for comparing groups on an outcome while accounting for specified covariates. In a randomized trial, it is commonly used to estimate a treatment contrast with adjustment for variables included in the model. This is general statistical context; the variables and exact model used for this trial are not reported in the registry record. The reported ANCOVA estimate is an estimated treatment difference, rather than the simple unadjusted difference between the displayed group means.

The sponsor’s ANCOVA estimate is -10.48 and its 95% confidence interval is -12.34 to -8.63. Its p-value is < 0.001. The recalculated unadjusted contrast is -11.7, its 95% confidence interval is -13.16 to -10.24, and its unadjusted p-value is <0.001. The distinctions in method and reported precision matter: the unadjusted calculation is a descriptive check from the posted summaries, while the registry’s reported model-based result is the sponsor analysis.

How should a p-value be read?

In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. A small p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The registry gives a p-value for the sponsor’s ANCOVA analysis and a separate unadjusted p-value for the recalculation. The test details and full assumptions for the sponsor analysis are not reported in the registry record.

The p-value should be read alongside the estimate and confidence interval. An estimate conveys the direction and scale of the contrast, while the interval conveys uncertainty about its precision under the analysis. Neither a small p-value nor a confidence interval that excludes zero provides a complete account of benefit, harms, or relevance to patients.

Why can variation and missing values matter?

In general, more variability in a continuous outcome makes a group contrast less precise when other features of the design remain similar. Standard deviations are therefore useful context for understanding the spread of observed changes. This trial’s primary group standard deviations were 8.6 for semaglutide and 5.6 for placebo.

Missing outcome values can also affect interpretation. The primary outcome description says the analyzed number means participants with available data, but the record does not report how many randomized participants lacked primary outcome data, why values were unavailable, or how missingness was handled in the sponsor’s model. General statistical guidance is that missing-data assumptions can influence estimates; the specific assumptions used for this trial are not reported in the registry record.

What does the planning calculation represent?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They show participants per arm for 80% or 90% power when the effect to detect is a stated fraction of the observed effect. These are planning illustrations based on the observed result, not the original trial design assumptions. They are not observed power. In general, targeting a smaller effect requires more participants to achieve the same planned power, all else equal.

These sample-size illustrations are separate from the trial’s observed analysis. They do not establish that the trial was designed using the observed effect, and they do not replace the sponsor’s analysis. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

11. Confidence Intervals and Precision

The sponsor’s 95% confidence interval for the estimated treatment difference runs from -12.34 to -8.63, around an estimate of -10.48. The unadjusted recalculation has a 95% confidence interval from -13.16 to -10.24, around an estimate of -11.7. Both intervals lie on the negative side of zero. The intervals describe uncertainty in their respective estimates under their respective analyses; they should not be treated as interchangeable because the estimates come from different methods.

In general, a confidence interval is a range of values compatible with the data and the statistical model at the stated confidence level. It is not a range containing a fixed proportion of individual participant responses. Nor does a 95% confidence interval mean there is a 95% probability that the particular interval contains the true value. The interpretation relies on the analysis assumptions, which are not fully detailed for the sponsor’s ANCOVA in the registry record.

The interval widths provide information about statistical precision: a narrower interval indicates greater precision under the analysis, while a wider interval indicates more uncertainty. Precision is not the same as clinical importance. A precisely estimated contrast can still require clinical context, and the registry does not report a threshold for clinically important body-weight change for this endpoint.

The sponsor’s estimate and the unadjusted recalculation differ in magnitude, but both indicate a negative group contrast. The registry record does not report enough detail to attribute the difference to particular covariates, assumptions, or missing-data procedures. The sponsor’s analysis is the reported trial analysis; the simple recalculation is an additional unadjusted comparison based on posted summary statistics.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants and not total events. They are calculated as illustrations using the observed effect and the stated planning assumptions: a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrated target effects are 100%, 75%, and 50% of the observed effect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm for a design that would have an 80% chance of detecting the selected effect under the calculation assumptions, if that effect were the true effect and the model assumptions held. The 90% power column uses a higher target chance of detecting that effect, and therefore gives a larger planning number for the same effect fraction. Power is a design property under assumed conditions, not a guarantee that a study will find a statistically significant result.

Smaller effects require more participants to detect with the same planned power, all else equal. Thus, planning for 50% of the observed effect produces larger per-arm figures than planning for the full observed effect. The figures are sample-size illustrations based on the effect observed in this trial; they are not observed power and should not be read as the number the trial actually needed or as evidence of its original design plan.

The curve’s planning meaning is the same: it relates the target effect size to the number of participants required under the stated assumptions. It does not show a new observed trial outcome. Any use of such planning estimates for a future study would require assumptions appropriate to that future question and population.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -11.700; pooled standard deviation σ = 7.765.
2. n = 2 × (1.96 + 0.842)² × 7.765² / -11.700² = 6.9, rounded up to 7 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -11.7                      # observed difference in means
sigma <- 7.76504018383703                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5064735)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 7 (80% power), 10 (90% power)
 75% of observed effect: n per arm = 13 (80% power), 17 (90% power)
 50% of observed effect: n per arm = 28 (80% power), 38 (90% power)
power.t.test: 8 
Simulated power at n = 7 per arm: 0.733 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as ANCOVA, with an estimated treatment difference of -10.48, a 95% confidence interval from -12.34 to -8.63, and p < 0.001. The simple unadjusted re-calculation from the posted group summaries gives a mean difference of -11.7, a 95% confidence interval from -13.16 to -10.24, and an unadjusted p-value <0.001.

These estimates are not identical because they are not the same analysis: the registry result is model-based, while the recalculation compares the posted summaries without adjustment. The record does not report the full ANCOVA model specification, so it is not possible to identify from the registry record which modeling choices account for the difference. Both estimates are negative, and both confidence intervals exclude zero, but they should remain labeled by their analysis method.

The registry’s reported ANCOVA result is the sponsor’s own analysis of the trial endpoint. The recalculation is a secondary statistical check, not a replacement for that analysis. The record indicates no flagged discrepancy, and the posted sponsor result should be read as the primary reported analysis. The recalculation is useful for understanding the unadjusted contrast between the displayed group summaries, but it cannot recover the adjusted analysis from summary data alone.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, time points, subgroups, or statistical comparisons. In general, conducting many tests without adjustment increases the chance that at least one result will appear statistically notable even when no corresponding effect exists. The registry lists a broad set of secondary outcomes, including body-weight thresholds and several measures of physical function, pain, stiffness, and waist circumference. The record does not report whether the investigators used a multiplicity adjustment, a prespecified testing hierarchy, or another procedure to control the overall interpretation of these comparisons.

The primary endpoint has a reported sponsor ANCOVA result. That result should be distinguished from the unadjusted secondary comparisons. The registry record does not report a complete statistical analysis plan, the timing of any analysis plan decisions, or whether any interim analyses were conducted. Those details are not reported in the registry record and should not be inferred from the outcome listings.

The primary outcome population is described as the full analysis set, including all randomized participants according to the intention-to-treat principle. For the endpoint, the record says the analyzed number is the number with available data. This description does not explain how missing values were handled, whether an imputation method was used, or whether sensitivity analyses were conducted. These missing-data procedures are not reported in the registry record.

Missing data matter because the observed participants may not fully represent all randomized participants if availability is related to outcome or treatment. This is a general statistical concern, not a claim about why data were unavailable in this trial. The registry record does not report reasons for missingness or enough detail to assess the assumptions underlying the primary analysis.

The record does not report a sample-size justification, the assumptions used for the original design, or an explicit target effect for the primary endpoint. The planning illustrations based on the observed effect are not evidence of the trial’s original design plan. Without the original planning documentation, the relationship between enrollment and the intended power cannot be assessed from the registry record alone.

16. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sleeve gastrectomy (1.5%), breast cancer metastatic (0.7%), cholecystitis acute (0.7%), prostate cancer (0.7%), abdominal abscess (0.7%).

The registry lists serious adverse events for the semaglutide group among 269 participants at risk and for the placebo group among 135 participants at risk. Serious adverse events affected 27 participants in the semaglutide group and 11 in the placebo group. The record lists 0 deaths in each group. These are counts reported by the registry, not a causal comparison adjusted for differences in exposure or follow-up.

The listed serious-event terms and percentages include sleeve gastrectomy at 1.5%, and breast cancer metastatic, acute cholecystitis, prostate cancer, abdominal abscess, and acute kidney injury each at 0.7%. These are the registry’s listed terms; the record does not give enough detail to determine whether each event was considered related to study treatment.

The registry also reports other adverse events: 128 affected participants among 269 at risk in the semaglutide group and 51 among 135 at risk in the placebo group. Serious and other adverse-event counts are different categories in the record and should not be combined. Counts alone do not describe event timing, duration, severity beyond the listed classification, or causal attribution. The trial’s safety figures are descriptive and do not replace a full review of adverse-event definitions and follow-up.

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

The primary result describes the average percentage change in body weight over the stated treatment period in randomized groups of people with obesity and knee osteoarthritis. The posted group means were -14.2 for semaglutide and -2.5 for placebo. The sponsor’s ANCOVA estimate was -10.48, with a 95% confidence interval from -12.34 to -8.63. These figures support a statistical contrast between the randomized groups under the reported analysis.

The result does not mean that every participant experienced the group-average change. It does not describe the full range of individual outcomes, and it does not identify which participant characteristics may be associated with different responses. The registry record does not report an individual-response analysis for the primary outcome.

The result also does not, by itself, establish the clinical importance of the observed difference. The registry does not report a minimal clinically important difference for the primary endpoint. The primary measure is body-weight change; knee symptoms and function are represented through separate secondary outcomes. A body-weight result alone should not be treated as a complete account of those other outcomes.

Statistical evidence is also not a guarantee of the same result in another population or study setting. The trial concerned people with obesity and knee osteoarthritis and included specific eligibility restrictions. The results should be understood in that context rather than generalized automatically to groups not represented by the trial.

Finally, the reported analysis has limitations in what can be assessed from the registry record. Full ANCOVA details, missing-data procedures, multiplicity handling, and the original sample-size justification are not reported in the registry record. These omissions do not erase the posted estimates, but they limit how completely the analysis assumptions and broader evidential context can be evaluated.

18. Why This Trial Matters Statistically

This trial is statistically informative because it uses a randomized, parallel-group comparison to examine a continuous primary outcome over a defined treatment period. Randomization supports comparison of assigned groups, while the reported group summaries make the scale and variability of the observed weight changes visible. The sponsor’s ANCOVA result and the unadjusted recalculation also illustrate why the analysis method should be named when reporting a treatment contrast.

The contrast between the two estimates is a useful reminder that an adjusted model-based estimate and an unadjusted summary-data calculation are not interchangeable. The reported estimate, confidence interval, and p-value should be interpreted as the sponsor’s ANCOVA analysis; the recalculation answers a simpler descriptive question. Statistical reporting is clearer when these distinctions are explicit.

The study also includes a broad set of secondary outcomes related to function, pain, stiffness, and body measurements. This can help readers see how the primary endpoint sits within a wider set of measured domains. At the same time, multiple outcomes make prespecification and multiplicity control important for distinguishing confirmatory evidence from exploratory patterns. Those procedures are not reported in the registry record.

Finally, the record makes a distinction between the full analysis set and the number with available data for the endpoint. That distinction is important when interpreting randomized trial results: the analysis population label does not alone explain how missing outcomes were handled. Complete reporting of analysis choices would help readers evaluate the robustness and precision of the result.

19. 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 registry record does not report the complete ANCOVA specification, including the variables included in the model. This limits independent assessment of the adjusted estimate and makes it impossible to explain the difference between the sponsor’s estimate and the simple unadjusted recalculation in detail. The recalculated result relies on posted summary statistics and cannot reproduce participant-level analyses.

The primary endpoint analysis includes participants with available data, while the record defines the full analysis set as all randomized participants under the intention-to-treat principle. The number of missing primary values, reasons for missingness, missing-data method, and sensitivity analyses are not reported in the registry record. This limits evaluation of the potential effect of missing outcome data.

The registry does not report the original sample-size justification or the assumptions used to plan enrollment. The sample-size illustrations based on the observed effect do not answer whether the original trial was adequately designed for a particular effect. The statistical analysis plan, interim analysis details, and any multiplicity strategy are also not reported in the registry record.

The registry’s condition listing names obesity, while the study title and summary describe participants with obesity and knee osteoarthritis. The available record does not provide a full account of the clinical characteristics of the analyzed population. It also does not report a minimal clinically important difference for the primary endpoint, limiting interpretation of clinical importance based on the statistical estimates alone.

Safety listings are presented as counts and selected event terms. The record does not provide, in the registry record reported for this analysis, sufficient detail about event timing, treatment attribution, or the complete clinical context for each event. These limits call for a descriptive reading rather than causal conclusions from the counts.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Research Study Looking at How Well Semaglutide Works in People Suffering From Obesity and Knee Osteoarthritis — NCT05064735.
• Registry record last updated 2025-11-17; status last verified 2025-11.
• Results first posted 2024-08-13.
• 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.

23. Record Summary

The registry records a completed phase 3, randomized, triple-masked, parallel-group trial sponsored by Novo Nordisk A/S, with enrollment of 407. It compared once-weekly subcutaneous semaglutide 2.4 mg with placebo, with both groups receiving a reduced-calorie diet and increased physical activity. The primary endpoint was mean percentage change in body weight from baseline (week 0) to end of treatment (week 68).

The sponsor’s ANCOVA analysis reported an estimated treatment difference of -10.48, with a 95% confidence interval from -12.34 to -8.63 and p < 0.001. A simple unadjusted recalculation from the posted summaries gave a mean difference of -11.7, with a 95% confidence interval from -13.16 to -10.24 and p <0.001. These are distinct analyses and should be read as such.

The registry also lists secondary outcomes and adverse-event counts. The original sample-size justification, detailed missing-data methods, full ANCOVA model, and multiplicity procedures are not reported in the registry record.