Patient Preference and Satisfaction With Insulin Glargine (Lantus) Solostar Pen vs Conventional Vial-Syringe Method of Lantus Injection Therapy in Patients With Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Patient Preference and Satisfaction With Insulin Glargine (Lantus) Solostar Pen vs Conventional Vial-Syringe Method of Lantus Injection Therapy in Patients With Type 2 Diabetes Mellitus (NCT01226043), a randomized phase 4 study. The primary outcome is Patient Overall Preference.

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, open-label, multicenter study using a crossover model. Its central comparison was between two ways of delivering insulin glargine: the SoloSTAR pen and the conventional vial-and-syringe method. Because masking was listed as none, participants and healthcare professionals were not blinded to the delivery system in use. That matters especially for a preference outcome, which is directly based on participants’ reported experience and can be influenced by awareness of the device.

The primary preference assessment took place at week 4, at the end of the crossover phase. The study also included a re-randomization phase, with glucose and daily insulin-dose outcomes measured from week 4 to week 10, and an observational phase with outcomes extending to week 40. The registry describes healthcare professional recommendation as a secondary objective during the crossover phase, and includes safety assessment across study phases. It does not report the device sequence or the detailed timing of every crossover treatment period, so those aspects cannot be reconstructed from the registry record.

The registry lists 405 enrolled participants. The primary preference results are reported for 388.0 participants in each device group. Those reported analysis counts should not be read as the total enrolled population: the primary analysis population had additional requirements, including receiving both delivery systems and completing the questionnaire. The registry does not provide enough information to reconcile every difference between enrollment and the analyzed populations.

The study was completed and sponsored by Sanofi. Its design addresses preference between delivery systems and also includes later measures of fasting plasma glucose, glucose-goal attainment, insulin dose, and adverse events. The study’s primary question remains a preference question; the additional outcomes do not change the endpoint’s meaning.

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 623 patients were screened of whom 405 insulin naïve patients were randomized for the crossover phase. The most common reason for non randomization was glycosylated hemoglobin (HbA1c) value out of range at the screening visit as defined per protocol.

4-week Crossover Phase - Period 1

Reasons for not completing this period:

4-week Crossover Phase - Period 2

Reasons for not completing this period:

6-week Re-randomization Phase

Reasons for not completing this period:

30-week Observational Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified intent-to-treat (mITT) population for the Patient Preference Questionnaire analysis consisted of all randomized patients who received at least one dose of Lantus via both insulin delivery systems and completed the questionnaire at Week 4. This analysis included patients who answered question 14d.

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: Baseline characteristics provided for the population randomized for the first phase of the study: crossover phase.

6. Primary Endpoint

The registry lists the primary outcome as Patient Overall Preference, measured over At week 4 (end of crossover phase).

The primary endpoint was patient overall preference at week 4, the end of the crossover phase. Participants answered an overall-preference question about each insulin delivery system using a five-point scale: 1 meant not preferred and 5 meant always preferred. The registry reports the endpoint as a mean score for each system and a net mean difference between them, with a 95% confidence interval.

Preference is useful when the research question concerns how participants view or experience alternative delivery methods. A rating can summarize the direction and strength of stated preference across the analyzed population. It is not, by itself, a measure of glucose control, safety, adherence, or clinical benefit. Those are separate questions, and the registry lists distinct outcomes for some of them.

The primary analysis population was not every enrolled participant. It consisted of randomized participants who received at least one dose through both delivery systems and completed the questionnaire at week 4. This definition makes completion and exposure to both systems conditions for inclusion. The registry record does not report further details of questionnaire scoring beyond the stated scale and the difference in scores obtained from the overall-preference question.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean score describe?

A mean is a summary of the observed scores in an analyzed group. Here, the scale is bounded by its stated response options, from 1 to 5. A group mean gives a compact account of ratings, but it does not show how ratings are distributed among individuals. Participants may have given varied answers even when the group mean is relatively high or low. The registry does not report the full response distribution for the primary endpoint.

How should the confidence interval be read?

A confidence interval expresses statistical uncertainty around an estimated quantity under the analysis assumptions. The sponsor-reported interval for the net preference difference is 2.15 to 2.44 at the 95% confidence level. In general, an interval is not a guarantee that the true value lies within its limits, and it does not describe variation among individual participants. Its width and position relative to zero help readers assess precision and whether the estimate is compatible with no mean difference under the stated analysis. The registry identifies ANOVA as the reported method for the primary comparison.

What does the p-value contribute?

The sponsor reported p < 0.001 for the primary comparison. In general, a p-value measures how incompatible the observed data are with a specified null model, assuming the model and analysis conditions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. The estimate and confidence interval provide complementary information about magnitude and precision.

Why do crossover and open-label features matter?

A crossover design allows participants to experience both compared systems, so the preference question directly concerns experience with each. The primary analysis population explicitly required exposure to both systems. Crossover designs can raise questions about treatment sequence, period effects, and carryover from one period to another; detailed handling of those issues is not reported in the registry record. Open-label status means participants knew which delivery system they used. That is relevant to a self-reported preference endpoint, although the registry does not quantify any effect of awareness on the ratings.

What are the secondary re-calculations?

The posted secondary arm summaries include least-squares means with standard errors for continuous outcomes and reported percentages for the binary glucose-goal outcome. The recalculated comparisons are simple unadjusted estimates from those posted summaries. For continuous outcomes, the comparison is expressed as a mean difference; for the binary outcome, it is expressed as a risk difference. These calculations do not reproduce a full trial analysis if that analysis used additional covariates, repeated-measures structure, or other model features. The registry does not report sponsor analyses for these three outcomes, so the recalculations should be read as descriptive statistical checks rather than as a substitute for the trial’s full statistical analysis.

A standard error describes the uncertainty of an estimated mean, rather than the spread of individual observations. When a comparison is reconstructed from arm-level standard errors, the calculation relies on assumptions about how those summaries relate to the comparison. The reported recalculation marks the pooled standard deviation as approximate for the continuous endpoints. General statistical caution is warranted: approximate calculations can differ from a model-based analysis that uses participant-level data and accounts for the study design.

Why can over-dispersion matter?

For a binary outcome, a simple binomial model assumes that the variability in observed outcomes is adequately represented by the event probability and sample size. In general, over-dispersion means the data vary more than that simple model expects. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for the extra variability. The registry does not report whether over-dispersion was assessed or how the sponsor modeled the binary secondary endpoint.

How should the planning illustrations be understood?

The planning illustrations use the observed effects, a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They show participants per arm for 80% power and participants per arm for 90% power under the stated fractions of the observed effect. These are planning illustrations, not the trial’s original design justification and not observed power. The registry does not report the assumptions behind the trial’s original sample-size planning. When an observed comparison is close to no difference, planning around that small observed effect can produce very large illustrative sample requirements; such outputs are sensitive to the estimated effect and should not be read as definitive design recommendations.

10. Analyses Reported by the Sponsor

The primary preference comparison is a sponsor-reported analysis using ANOVA. The posted estimate is a net mean difference of 2.3, with a 95% confidence interval from 2.15 to 2.44 and p < 0.001. The reported arm means are 4.75 for SoloSTAR and 2.45 for vial and syringe. These figures form the principal inferential result for the primary endpoint; the simple recalculations discussed for selected secondary outcomes do not replace it.

The registry does not report sponsor analyses for the fasting plasma glucose change, glucose-goal percentage, or daily dose change outcomes discussed in the secondary statistical material. Recalculations for those outcomes use posted summary statistics and are unadjusted. They may not reproduce a full analysis based on participant-level data or account for features of the trial design. No discrepancy is flagged between a sponsor analysis and a recalculation in the registry information. Where a sponsor result is reported, it should remain the primary reference for that analysis rather than an unadjusted reconstruction.

The registry record does not describe the full statistical analysis plan, including model specifications beyond the reported ANOVA for the primary comparison. It is therefore not possible to assess from the record alone whether other planned adjustments or sensitivity analyses were used.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and describes multiple objectives across the crossover, re-randomization, and observational phases. The outcomes include preference, healthcare professional recommendation, glucose measures, insulin dose, HbA1c, discontinuation, and safety. With several outcomes and timepoints, multiplicity is an important interpretive issue: repeated testing can increase the chance that at least one result appears unusual by chance. The registry record does not report a multiplicity-adjustment method, a hierarchy for testing outcomes, or which secondary results, if any, were designated confirmatory.

The record specifies a modified intent-to-treat population for the primary preference questionnaire analysis: randomized participants who received at least one dose through both systems and completed the questionnaire at week 4. It does not give a complete account of all analysis populations for every outcome, nor explain how participants with missing measurements were handled. Imputation, exclusion rules beyond the primary population definition, and sensitivity analyses for missing data are not reported in the registry record.

These omissions matter because the primary endpoint depends on questionnaire completion and the secondary outcomes have different analysis counts. The observed population for an outcome may differ from enrollment, and estimates can be affected if missingness is related to participants’ outcomes or treatment experience. General statistical methods can address some missing-data concerns, but the appropriate interpretation depends on the assumptions and procedures actually used. Those procedures are not reported in the registry record.

The registry also does not report an interim-analysis plan, stopping boundaries, or the statistical plan in enough detail to assess them. Their absence from the registry record should not be taken as evidence that a procedure was or was not used; it means the record does not allow that assessment.

12. Safety Results

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

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: non-cardiac chest pain (1.3%), atrial fibrillation (1.3%), angina unstable (0.7%), arthralgia (0.7%), bipolar i disorder (0.7%).

The registry reports serious adverse events by study phase and delivery system. During the crossover phase, serious adverse events affected 4 of 396 participants in the SoloSTAR group and 1 of 399 in the vial-and-syringe group. In the re-randomization phase, the corresponding counts were 1 of 165 and 0 of 165. During the observational phase, the counts were 16 of 159 and 14 of 153.

These are phase-specific counts, not one simple parallel-group comparison across the whole study. The crossover and later-phase populations and exposure periods differ, so the counts should be interpreted within their stated phase rather than added together or compared as though every participant contributed under identical conditions. The registry also reports other adverse events separately, but those are not the same category as serious adverse events. Death counts are not reported in the registry record.

The registry does not provide enough detail to establish whether differences in these counts reflect treatment, exposure time, participant characteristics, or chance. Safety figures describe what was recorded in the study; they do not by themselves establish a causal relationship or settle comparative safety.

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

The primary result is evidence about stated preference among participants who experienced both delivery systems and completed the week 4 questionnaire. The group-level scores and the sponsor-reported comparison indicate higher preference ratings for SoloSTAR than for vial and syringe in that analysis population. The confidence interval gives a relatively narrow range for the reported mean difference under the sponsor’s analysis, and the reported p-value indicates strong incompatibility with a no-difference null model under that analysis.

This result does not mean every participant preferred SoloSTAR, because group means do not reveal each individual’s response. Nor does it establish why participants rated the systems differently. The study was open label, and the primary endpoint was self-reported. The registry record does not provide information that would separate device usability, familiarity, expectations, or other influences on preference.

The result also does not answer whether one system changes glucose control, daily insulin requirements, HbA1c, adverse-event risk, or other clinical outcomes. Those questions are addressed by separate secondary outcomes, for which analysis details and multiplicity handling are not fully reported. Preference may be relevant to understanding participant experience, but it is not a substitute for those clinical measures.

Finally, the primary analysis applies to its defined population rather than automatically to every enrolled participant or to all people with type 2 diabetes. The requirement for exposure to both systems and completion of the questionnaire is part of the endpoint’s interpretation. The registry provides no basis for extending the findings beyond the study population and conditions described in the record.

14. Why This Trial Matters Statistically

This study illustrates why the endpoint should guide the statistical interpretation. A randomized comparison can produce a clear difference on a patient-preference scale without establishing a difference on a clinical measure. The primary result answers a focused question about reported preference at the end of the crossover phase; the later glucose, dose, and HbA1c outcomes address separate questions and timeframes.

It also highlights the role of analysis populations. Although the registry lists 405 enrolled participants, the primary questionnaire analysis is defined by exposure to both devices and questionnaire completion, and reports 388.0 participants in each device group. Readers need to understand who contributed to an endpoint before interpreting its estimate. A clear population definition helps, but missing-data procedures and sensitivity analyses are also important for judging how robust the result may be.

The crossover design makes within-study experience with both delivery approaches central to the preference question, while open-label status is especially relevant for a subjective rating. These features are not flaws by themselves; they identify the context in which the result should be read. The absence of reported sequence and carryover details limits deeper assessment of the design’s statistical handling.

Finally, the record illustrates the difference between a sponsor-reported analysis and an unadjusted recalculation from summary statistics. Recalculations can make secondary results easier to inspect, but they cannot substitute for a full analysis plan or participant-level model. The primary result and secondary comparisons therefore warrant different levels of confidence and should not be merged into a single claim.

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.

Several trial-specific limitations constrain interpretation. First, the primary endpoint was subjective and the study was open label, with no masking. Participants knew which delivery system they were using, which is directly relevant when the outcome is stated preference. The registry does not report whether participants had prior experience with either system or whether familiarity was assessed.

Second, the primary analysis required participants to receive at least one dose through both systems and complete the questionnaire. This creates an analysis population narrower than everyone enrolled. The registry record does not report the reasons for non-completion, the handling of missing questionnaire items, or sensitivity analyses that would show how missing data might affect the preference estimate.

Third, the registry does not describe the treatment sequence, period-specific analysis, or handling of possible carryover in enough detail to assess those crossover-design issues. It also does not report the full statistical analysis plan, the original sample-size justification, or a multiplicity strategy for the many secondary outcomes. These are limitations of the available record and should not be treated as proof that such procedures were absent from the conduct of the study.

Fourth, the secondary recalculations are unadjusted and based on posted summaries. They may not capture features of the original analyses, and the registry does not report sponsor analyses for those outcomes. The later-phase results also arise from populations that differ from the primary preference population. Finally, the safety counts are reported by phase and should not be interpreted as a single uniform comparison across all participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Patient Preference and Satisfaction With Insulin Glargine (Lantus) Solostar Pen vs Conventional Vial-Syringe Method of Lantus Injection Therapy in Patients With Type 2 Diabetes Mellitus — NCT01226043.
• Registry record last updated 2013-08-12; status last verified 2013-07.
• Results first posted 2013-07-30.
• 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

NCT01226043 was a completed, phase 4 randomized, open-label crossover study sponsored by Sanofi. It enrolled 405 participants with type 2 diabetes and compared insulin glargine delivered by SoloSTAR pen with delivery by vial and syringe. The primary endpoint was overall patient preference at week 4, assessed on a scale from 1, not preferred, to 5, always preferred.

The sponsor-reported primary comparison favored higher preference scores for SoloSTAR, with a net mean difference of 2.3, a 95% confidence interval from 2.15 to 2.44, and p < 0.001. The registry also lists secondary outcomes covering glucose, insulin dose, HbA1c, discontinuation, and safety. Some secondary comparisons are available only as unadjusted recalculations from posted summaries. The registry record does not report the full analysis plan, missing-data procedures, or multiplicity handling.