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. 2025 Jul 31;27(10):5498–5505. doi: 10.1111/dom.16592

HbA1c reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis

Tina Vilsbøll 1,2, Maciej T Malecki 3, Palash Sharma 4, Vivian T Thieu 4, Krishna Karthik Chivukula 4, Jacek Kiljanski 4,✉
PMCID: PMC12409195  PMID: 40746012

Abstract

Aim

Tirzepatide is a dual glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) receptor agonist for type 2 diabetes, chronic weight management and obstructive sleep apnoea (in the US). To assess the contribution of weight loss (WL) to the observed glycaemic effect, we performed mediation analysis of three randomized, controlled, parallel, 4‐arm SURPASS(S)‐trials; 1, 2 and 5, for a total of 2831 participants.

Materials and Methods

WL dependent (WL‐D) and WL independent (WL‐IND) effects on comparator‐adjusted glycated haemoglobin A1c (HbA1c) reduction at Week 40 were estimated using mediation analysis, adjusted for baseline HbA1c and study‐specific stratification factors.

Results

The difference in mean HbA1c change from baseline at 40 weeks (total effect) between tirzepatide and the placebo group ranged from −20.0 to −14.6 mmol/mol, and that between tirzepatide and semaglutide (1 mg) ranged from −5.1 to −1.9 mmol/mol. In the placebo‐controlled trials, 12%–27% of the difference in HbA1c change between tirzepatide dose arms and placebo was estimated as being mediated through WL when given as monotherapy (S1), and 25%–45% when on the background of insulin with or without metformin (S5). Compared with semaglutide, 54%–71% of the difference in HbA1c change between tirzepatide and semaglutide was estimated as being WL‐D.

Conclusion

The tirzepatide‐induced HbA1c reductions from baseline, compared with placebo or semaglutide, were mediated through both WL‐D and WL‐IND effects. Estimated contributions of WL to the difference in glycaemic efficacy varied and were highest when tirzepatide was compared with semaglutide and less pronounced when compared with placebo. These results help to understand that other factors beyond weight reduction contribute to HbA1c reduction with tirzepatide.

Keywords: HbA1c, mediation analysis, SURPASS studies, tirzepatide, weight loss, weight‐loss dependent effects, weight‐loss independent effects

1. INTRODUCTION

Tirzepatide is the first glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide 1 (GLP‐1) receptor agonist (GLP‐1RA) to have demonstrated substantial improvement of glycaemia and weight reduction as well as other metabolic benefits both in type 2 diabetes (T2D) and obesity. Phase 3 clinical trials (SURPASS‐1 (S1), −2 (S2), −3 (S3), −4 (S4), −5 (S5), −6 (S6)) with tirzepatide in participants with T2D showed significant reductions in glycated haemoglobin A1c (HbA1c) (primary outcome) (−20.8 to −28.5 mmol/mol (−1.9 to −2.6%)), and body weight (−6.2 to −13.9%) over 40 to 52 weeks, enabling some participants (13% to 62%) to achieve good glycaemic control (defined as HbA1c <39 mmol/mol (<5.7%)). 1 , 2 , 3 , 4 , 5 , 6 , 7

In Phase 2 and 3 clinical trials, tirzepatide has shown greater efficacy in reducing HbA1c levels and body weight compared with other once‐weekly GLP‐1RAs, dulaglutide 1.5/0.75 mg or semaglutide 1 mg. 2 , 8 , 9 There is interest in explaining potential mechanisms behind the superior efficacy of tirzepatide when compared with GLP‐1RAs. Tirzepatide shares glucoregulatory actions with GLP‐1RAs; however, improvements in beta cell secretory function, insulin sensitivity and inhibition of glucagon secretion are more pronounced with tirzepatide than with the GLP‐1 RA, semaglutide 1 mg. 10 , 11 It also remains unclear as to what extent the greater weight loss (WL) seen with tirzepatide drives improved glycaemic control. The SURPASS trials showed that tirzepatide was associated with reductions in both HbA1c and body weight, with a statistically significant but modest association between HbA1c and body weight change observed with tirzepatide; the degree to which weight reduction contributes to HbA1c reduction with tirzepatide was still to be investigated. 1 , 2 , 3 , 4 , 5 , 6 , 12 To elucidate the weight loss‐dependent (WL‐D) and ‐independent (WL‐IND) effects of tirzepatide on HbA1c reduction versus comparators, we performed mediation analysis of 3 global Phase‐3 SURPASS trials. Studies utilizing non‐insulin comparators (S1, S2 and S5) were chosen for the analysis to avoid the confounding effect of insulin therapy.

2. MATERIALS AND METHODS

2.1. Study design and participants

To estimate the relative contribution of WL to the overall improvement of glycaemic control, we performed post‐hoc mediation analysis of three 40‐week Phase 3 SURPASS studies (S1, S2 and S5). Studies that used insulin as a comparator were removed from the analysis due to insulin's potential for associated weight gain (S3, S4 and S6). A common 40‐week primary time point was selected for consistent assessment across the 3 SURPASS studies. The study design, key eligibility criteria and primary efficacy and safety results for S1, S2 and S5 have been published previously. 2 , 4 , 5 Briefly, the studies included adults with T2D inadequately controlled with diet and exercise. Eligible participants had an HbA1c of 7·0%–10.5% at screening and a body‐mass index (BMI) of ≥23 kg/m2 (S1 and S5) or ≥25 kg/m2 (S2). A key exclusion criterion was type 1 diabetes. Two of the trials were placebo‐controlled (S1 and S5) while the third trial was versus semaglutide 1 mg (S2). Individuals in S1 managed their T2D with diet and exercise alone, while S2 involved participants who were on metformin and S5 included those using basal insulin (insulin glargine) with or without metformin.

2.2. Statistical analysis

All analyses were conducted based on the efficacy analysis set (EAS), which included data obtained during the treatment period from randomized participants who took at least 1 dose of the study drug, excluding data after discontinuation of the study drug or initiation of any anti‐hyperglycaemic rescue medication. Additionally, participants who discontinued the study drug due to inadvertent enrolment were excluded. Mediation analysis was used to assess what proportion of the estimated treatment difference (ETD) in HbA1c with tirzepatide versus placebo or semaglutide was attributable to an indirect effect mediated by WL or to a direct effect. The model for estimation of WL‐D and WL‐IND effects on change from baseline in HbA1c at Week 40 included interaction between treatment and weight change, together with baseline HbA1c and pooled country as covariates. Additional factors were prior oral anti‐hyperglycaemic medication use (S1) and baseline metformin use (S5). All the estimated effects were reported using 5000 bootstrap iterations to accommodate the uncertainty of the estimates. Two‐sided p‐values of p < 0.05 were considered statistically significant. All the analyses were carried out using SAS (V.9.4).

3. RESULTS

3.1. Baseline characteristics and key demographics

Patient demographics are shown in Table 1. Baseline characteristics and demographics were well balanced between tirzepatide and comparators for each study. Over the 3 SURPASS studies, S1, S2 and S5, mean age was 54.1, 56.6 and 60.6 years, and mean BMI was 31.9, 34.2 and 33.4 kg/m2, respectively. At baseline, S1 participants had the lowest HbA1c and duration of diabetes (7.9% and 4.7 years, respectively) compared with S2 (8.3% and 8.6 years) and S5 (8.3% and 13.3 years). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in all treatment groups. Across the 3 studies, 79%–92% of participants completed the study treatment, with 85%–95% of participants completing the study.

TABLE 1.

Baseline characteristics and demographics.

Characteristic SURPASS‐1 (N = 478) SURPASS‐2 (N = 1878) SURPASS‐5 (N = 475)
Age, years, mean (SD) 54.1 (11.9) 56.6 (10.4) 60.6 (9.9)
Male, n (%) 247 (52) 882 (47) 264 (56)
Duration of diabetes, years, mean (SD) 4.7 (5.4) 8.6 (6.5) 13.3 (7.3)
Weight, kg, mean (SD) 85.9 (19.8) 93.7 (21.9) 95.2 (21.6)
BMI, kg/m2, mean (SD) 31.9 (6.6) 34.2 (6.9) 33.4 (6.1)
HbA1c, mean (SD)
mmol/mol 63.3 (9.5) 67.0 (11.3) 67.4 (9.3)
% 7.9 (0.9) 8.3 (1.0) 8.3 (0.9)
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Abbreviations: BMI, body mass index; HbA1c, glycated haemoglobin A1c, SD, standard deviation.

3.2. HbA1c and weight reduction with tirzepatide in SURPASS‐1, ‐2 and ‐5

Across the studies, HbA1c reductions from baseline ranged from −20.4 to −28.3 mmol/mol (1.9%–2.6%), and weight reductions from 6.2 to 12.4 kg, in participants receiving tirzepatide (Figure 1). In each study, changes in HbA1c and weight were greater with all doses of tirzepatide than with placebo or semaglutide 1 mg at endpoint (40 weeks) (Figure 1). At baseline, S1 participants had the lowest mean weight (85.9 kg) compared with S2 (93.7 kg) and S5 (95.2 kg). Across these 3 SURPASS studies, similar WL was observed with each respective dose of 5, 10 or 15 mg 2 , 4 , 5 (Figure 1). At Week 40, mean body weight reductions were dose‐dependent, with the greatest reductions seen in the 15 mg tirzepatide groups across the SURPASS programme. Body weight reductions continued without reaching a plateau.

FIGURE 1.

FIGURE 1

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HbA1c and body weight change from baseline to Week 40 in SURPASS‐1, ‐2, and ‐5. Data are LSM (SE) derived from MMRM, adjusted for baseline values and study stratification factors. **p < 0.001 vs. placebo or semaglutide. LSM, least squares mean; MMRM, mixed model for repeated measures; SE, standard error; TZP, tirzepatide.

3.3. Association between HbA1c reduction and weight change from baseline in SURPASS‐1, ‐2 and ‐5

In the placebo‐controlled trials (S1 and S5), 12%–27% of the difference in HbA1c change between tirzepatide dose arms and placebo was estimated as being mediated through WL when given as monotherapy (S1), and 25%–45% when on the background of insulin with or without metformin (S5). When compared with semaglutide 1 mg (S2), 54%–71% of the difference in HbA1c change between tirzepatide dose arms and semaglutide 1 mg was estimated as being mediated through WL (Figure 2).

FIGURE 2.

FIGURE 2

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Mediation analyses for comparator‐adjusted HbA1c reduction using weight loss as a factor at Week 40 in SURPASS‐1, ‐2, and ‐5 studies. Forest plot of weight loss‐dependent (WL‐D) and weight loss‐independent (WL‐IND) effects of TZP on change in HbA1c (mmol/mol) in (A) SURPASS‐1 and ‐5, and (B) SURPASS‐2 studies. mITT population (efficacy analysis set) of each study including on‐treatment data prior to use of rescue therapy. Participants were randomized 1:1:1:1 to TZP 5, 10, 15 mg or comparator. Primary endpoint was 40 weeks. Percentage values represent the percent of HbA1c reduction mediated by weight loss. CI, confidence interval; ETD, estimated treatment difference; MET, metformin; mITT, modified intent‐to‐treat; TZP, tirzepatide.

3.4. Subgroup analysis of HbA1c reduction and weight change from baseline in SURPASS‐2

To further elucidate the estimated impact of WL on changes in HbA1c, we further categorized participants from the S2 study into 2 WL and separately 2 HbA1c achieving groups, participants who lost at least 5% or 10% of their body weight, and separately, participants who achieved an HbA1c of ≤47.5 or ≤53 mmol/mol (≤6.5% or <7%). Smaller total participant N numbers in the S1 and S5 studies did not allow for this subcategorization. For participants who lost at least 5% body weight, 27% to 38% of the difference in HbA1c change between tirzepatide treatment and semaglutide 1 mg arms was estimated as being mediated through WL (Figure 3). While for those in the at least 10% body WL category, 20%–39% of the difference in HbA1c change between tirzepatide dose and semaglutide 1 mg arms was estimated as being mediated through WL (Figure 3). For participants who achieved an HbA1c of ≤53 mmol/mol (<7%), the relative contribution of WL was estimated at between 41% and 45%, while for those who reached an HbA1c ≤47.5 mmol/mol (≤6.5%), the contribution was greater for each dose and was between 43% and 53% mediated by WL (Figure 4).

FIGURE 3.

FIGURE 3

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Mediation analyses for comparator‐adjusted HbA1c reduction using weight loss as a factor at Week 40 in participants achieving ≥5% or ≥10% body weight loss (SURPASS‐2). Forest plot of weight loss‐dependent (WL‐D) and weight loss‐independent (WL‐IND) effects of TZP on change in HbA1c (%) in SURPASS ‐2 with subgroups for participants achieving ≥5% or ≥10% body weight loss at endpoint. mITT population (efficacy analysis set) including on‐treatment data prior to use of rescue therapy. Participants were randomized 1:1:1:1 to TZP 5 mg, 10 mg, 15 mg or comparator. Primary endpoint was 40 weeks. Percentage values represent the percent of HbA1c reduction mediated by weight loss. CI, confidence interval; ETD, estimated treatment difference; MET, metformin; mITT, modified intent‐to‐treat; n, number of participants; TZP, tirzepatide.

FIGURE 4.

FIGURE 4

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Mediation analyses for comparator‐adjusted HbA1c reduction using weight loss as a factor at Week 40 in participants achieving HbA1c ≤47.5 or ≤53 mmol/mol (≤6.5% or <7%) (SURPASS‐2). Forest plot of weight loss‐dependent (WL‐D) and weight loss‐independent (WL‐IND) effects of TZP on change in HbA1c (mmol/mol) in SURPASS ‐2 with subgroups for participants who achieved an HbA1c of ≤47.5 or ≤53 mmol/mol (≤6.5% or <7%) at primary endpoint. mITT population (efficacy analysis set) including on‐treatment data prior to use of rescue therapy. Participants were randomized 1:1:1:1 to TZP 5, 10, 15 mg, or comparator. Primary endpoint was 40 weeks. Percentage values represent the percent of HbA1c reduction mediated by weight loss. CI, confidence interval; ETD, estimated treatment difference; HbA1c, glycated haemoglobin A1c; MET, metformin; mITT, modified intent‐to‐treat; n, number of participants; TZP, tirzepatide.

4. DISCUSSION

We conducted the first mediation analysis to estimate the relative importance of WL in achieving significant glycaemic control improvements with tirzepatide. Tirzepatide significantly reduced HbA1c levels compared with both placebo and semaglutide 1 mg, and this mediation analysis showed that a substantial portion of this effect was mediated through WL. The magnitude of this estimated contribution varied between the studies.

The importance of WL for improvement of glycaemic control in T2D has been well established in clinical practice, and the ADA 2024 Standards of Care highlight the health benefits of WL for individuals with T2D. 13 , 14 , 15 , 16 , 17 Even modest WL goals of 3%–7% have shown improvements in glycaemic control, and WL of >10% is associated with disease‐modifying effects including cardiovascular risk reduction. 13 , 18 WL between 10% and 15% has shown enhanced improvements in HbA1c and fasting glucose levels, potentially promoting diabetes remission and additional cardiovascular benefits in lowering blood pressure and lipid profiles. 13 , 17 , 19 , 20 Data demonstrating the direct effect of WL on HbA1c reduction are limited. Gummesson et al. evaluated clinical trials data to quantify the impact of WL in individuals with obesity and/or overweight with T2D and developed the model which estimated that for each kg of mean WL, there is a mean HbA1c reduction of 0.1 percentage points. 21 The HbA1c‐lowering effect depended on baseline glycaemia. Authors of a retrospective, longitudinal cohort study using individuals from ambulatory US data found that average HbA1c reductions of 1.2% and 0.5% were observed among people who lost ≥15% of index weight in the 1‐year and 5‐year follow‐ups. 22

The introduction of tirzepatide, which triggers improvements in glycaemic control and WL, has sparked interest in understanding to what extent weight improvement may explain the HbA1c decrease observed in tirzepatide clinical trials. Treatment with tirzepatide has shown a significant, albeit modest, association between WL and HbA1c reduction, but no data existed on the impact WL might have. 12

In this post‐hoc analysis, the relative contribution of WL to the difference in glycaemic improvement was lowest in placebo‐controlled trials. In S1, conducted in individuals with the shortest history of T2D (4.7 years), who were treatment‐naive or had stopped treatment prior to the study, the contribution of WL on HbA1c reduction was 12%–27%. In S5, where participants had more advanced disease (duration of diabetes 13.3 years) and used basal insulin (with or without metformin) as background therapy, the impact of WL on HbA1c reduction was 25%–45%. In S2 (duration of diabetes 8.6 years), the relative contribution was 54%–71%, where semaglutide 1 mg was the comparator. Previous studies have shown that the duration of diabetes may impact the relative contribution of WL to observed improvements in glycaemic control. The duration of diabetes in S1 (placebo‐controlled) versus S2 (active comparator‐controlled) was nearly double (4.7 vs. 8.6 years), which may contribute to the greater effect attributable to WL observed for S1.

Additional differences between the studies may contribute to the observed difference in the contribution of WL to HbA1c reduction, including other baseline characteristics and the choice of GLP‐1 RA as a comparator in S2 versus placebo in S1.

Previous studies showed that the duration of diabetes may impact the efficacy of WL in contributing to improvements in glycaemic control measures, and further study is needed to detail the specific contribution of diabetes duration in combination with other patient and disease characteristics. 19 , 23

It is hypothesised that the reduction in HbA1c observed with WL may be an indirect effect, mediated by improvements in insulin sensitivity. Data from the Heise et al. and S1 and S2 trials illustrate that tirzepatide improves insulin sensitivity, which may contribute to weight‐mediated HbA1c reduction. 2 , 4 , 10 , 12 In S1, participants showed a 2%–12% decrease in fasting insulin and a 9%–23% decrease in homeostatic model assessment of insulin resistance (HOMA2‐IR), indicating enhanced insulin sensitivity. 24 While in S2, all doses of tirzepatide led to significant improvements in pancreatic beta cell function and insulin sensitivity alongside improved glycaemic control and substantial weight reduction. 11

According to Thomas et al., improvements in insulin sensitivity with tirzepatide 10‐mg and 15‐mg doses were only partially attributable to WL. 25 Their study found that WL explained only 13% and 21% of the improvement in insulin resistance (HOMA2‐IR) with tirzepatide 10‐mg and 15‐mg doses, respectively, suggesting that the effects of tirzepatide on insulin sensitivity are mediated through additional mechanisms beyond WL. 25

Also, the extent of WL may have varying impacts on insulin sensitivity with tirzepatide and GLP‐1RAs, as demonstrated in a recent study showing that insulin sensitivity increases more per unit of weight lost with tirzepatide compared with semaglutide 1 mg. 26 These improvements in insulin sensitivity likely contribute to the larger reductions in HbA1c observed with tirzepatide 15 mg compared with semaglutide 1 mg. This may partially explain the greater reductions in HbA1c seen in the S2 study for tirzepatide versus semaglutide 1 mg. Results of the analysis performed in subgroups of S2 suggested that contributions of WL to the overall improvements in glycaemia are independent of the robustness of WL and glycaemic response.

There are several clinical implications of the finding reported in this paper. Contribution of WL to the overall improvement of glycemia in T2D should be considered and discussed with patients who might benefit from understanding tirzepatide's mechanism of action and how WL associated with therapy might impact their overall metabolic control. They should also understand that improvement of glycaemia might not be driven entirely by WL, and losing weight is not a prerequisite for lowering HbA1c with tirzepatide. Other weight‐independent factors such as increased secretory response of beta cells and suppression of glucagon play an important role in lowering glycaemia. 10 This analysis exhibits several strengths that enhance the robustness and generalizability of its findings. The study benefits from large and balanced sample sizes across groups and a broad spectrum of disease, including participants with both shorter and longer durations of the disease. Additionally, the inclusion of participants with insulin‐naive T2D, those on multiple oral anti‐diabetic medications, and those on insulin therapy further strengthens the study. Finally, the trials included participants with a range of BMI values which collectively contribute to the reliability and applicability of the study's findings.

This study has several limitations that should be considered when interpreting the results. Firstly, the use of post‐hoc analysis introduces potential biases, as these analyses were not pre‐specified and were conducted after examining the data. This approach can lead to findings that may not be replicable in other datasets. Secondly, the mediation analysis employed in this study is inherently a statistical model. While it provides insights into the potential mechanisms linking WL and glycaemia, it relies on certain assumptions that, if unmet, could compromise the validity of the results. Lastly, it was not possible to quantify the direct impact of WL on glycaemic control within these studies. The inability to isolate this effect means that other confounding factors may have influenced the observed changes in glycaemic control, limiting the ability to draw definitive conclusions about the relationship between WL and blood sugar levels. Furthermore, in the SURPASS trials, we did not collect other factors that may affect both WL and improvement of glycaemia, such as food intake and dietary habits. These limitations highlight the need for cautious interpretation of the findings and suggest areas for future research to address these gaps. It is also important to consider that WL observed in these trials represents overall loss of weight without differentiating between the relative contributions of fat deposits, which have different metabolic impacts. In the paper by Heise et al., tirzepatide was shown to trigger primarily loss of fat versus Fat‐free mass; further, Gastadelli et al. have shown that treatment with tirzepatide triggers loss of ectopic fat deposits– liver fat and visceral adipose tissue– which are known to be linked to insulin resistance. 27 , 28 Our study cannot elucidate the effects of loss of specific fat deposits on glycaemic control. Further study is required to better elucidate the potential mechanisms of WL‐IND effects on insulin sensitivity during treatment with tirzepatide, and to understand specific patient characteristics, such as duration of diabetes and/or metabolic and inflammatory markers associated with response.

5. CONCLUSION

In this post‐hoc mediation analysis, the tirzepatide‐induced HbA1c reduction from baseline, compared with placebo or semaglutide 1 mg, was mediated through both WL‐D and WL‐IND effects. Contributions of WL to the difference in glycaemic efficacy varied and were estimated to be highest when tirzepatide was compared with GLP‐1RA semaglutide 1 mg. The estimated impact of WL was less pronounced when tirzepatide was compared with placebo.

AUTHOR CONTRIBUTIONS

All authors contributed to the interpretation of the results. Palash Sharma was responsible for the data analysis. All authors participated in the drafting and critical review of the manuscript and gave approval for the final version to be published.

FUNDING INFORMATION

This study was funded by Eli Lilly and Company.

CONFLICT OF INTEREST STATEMENT

TV has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, Astra‐Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, Novo Nordisk, Carmot/Roche, Regor, Sanofi, Sun Pharmaceuticals, and Zealand Pharma. MTM has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Abbott, AstraZeneca, Ascentia, Adamed, Bayer, Berlin‐Chemie, Boehringer Ingelheim, Dexcom, Eli Lilly and Company, Krka, Medtronic, Merck, Novo Nordisk, Sanofi, and Servier. PS, VTT, KC, and JK are all employees and shareholders of Eli Lilly and Company.

PEER REVIEW

The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer‐review/10.1111/dom.16592.

ACKNOWLEDGEMENTS

The authors thank the participants and the study teams and investigators who cared for them. The authors would like to thank Claudia Nicolas for preliminary data analysis and Gary Grant PhD (Eli Lilly and Company) for writing/editorial assistance.

Vilsbøll T, Malecki MT, Sharma P, Thieu VT, Chivukula KK, Kiljanski J. HbA1c reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis. Diabetes Obes Metab. 2025;27(10):5498‐5505. doi: 10.1111/dom.16592

DATA AVAILABILITY STATEMENT

Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.

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