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. 2025 Mar 13;27(6):3223–3232. doi: 10.1111/dom.16337

Time spent in glycaemic control with sustained body weight reduction with tirzepatide: A post hoc analysis of the SURPASS clinical trial programme

Brandon K Bergman 1, Julio Rosenstock 2, W Timothy Garvey 3, Rachel L Batterham 1,4, Yanyun Chen 1, Minzhi Liu 5, Palash Sharma 1, Chrisanthi A Karanikas 1, Vivian T Thieu 1,✉
PMCID: PMC12046485  PMID: 40083081

Abstract

Aims

This participant‐level exploratory analysis assessed the continuous time spent in glycaemic control and/or with sustained weight reductions with tirzepatide treatment in participants with type 2 diabetes (T2D) from the SURPASS programme.

Materials and Methods

Participants (N = 6246) from SURPASS 1–5 were randomized to once weekly tirzepatide (5, 10 or 15 mg) or comparator (once weekly placebo, once weekly semaglutide 1 mg, insulin degludec or insulin glargine). Continuous time spent with HbA1c < 7.0% (53 mmol/mol), ≤6.5% (48 mmol/mol) and ≥5% body weight reduction and combined HbA1c ≤ 6.5% (48 mmol/mol) with a ≥5% body weight reduction were assessed through 40 weeks (SURPASS‐1, ‐2, and ‐5) or 52 weeks (SURPASS‐3 and ‐4). The non‐parametric Wilcoxon rank sum test was used to compare the median duration of continuous time spent in control, and logistic regression was used to analyse the proportion of participants achieving glycaemic control and body weight reduction at any time points or at the end of the primary study period.

Results

Median time spent with HbA1c < 7.0% (53 mmol/mol) was 80% (tirzepatide) versus 70% (semaglutide) and 0% (placebo) of the treatment duration in 40‐week studies, and 77%–85% (tirzepatide) versus 62% (insulin degludec) and 23% (insulin glargine) of the treatment duration in 52‐week studies (p < 0.001). Time spent with HbA1c < 7.0% (53 mmol/mol) was generally similar across all tirzepatide doses in each study. Dose‐dependent increases in time spent with ≥5% body weight reduction were observed with tirzepatide (median time spent: 20%–77% with tirzepatide versus 25% with semaglutide 1 mg) (p < 0.001). Tirzepatide‐treated participants experienced longer time spent with HbA1c ≤ 6.5% (48 mmol/mol) and ≥5% body weight reduction versus semaglutide (median: 35%–60% vs. 7%) (p < 0.001).

Conclusions

In this post hoc analysis, people with T2D experienced substantially longer continuous time in glycaemic control and more sustained body weight reductions with tirzepatide versus placebo and active comparators.

Keywords: body weight control, glycaemic control, tirzepatide, type 2 diabetes

1. INTRODUCTION

Type 2 diabetes (T2D) is a complex chronic disease that benefits from progressive treatment intensification to reach and maintain targeted therapy goals. Recent guidelines recommend tailoring therapy based on an individual's lifestyle and clinical characteristics, such as age, duration of disease and presence of comorbidities, and reassessing regularly to ensure patients' needs are being met. 1 , 2 , 3 For the majority of nonpregnant adults with T2D, a glycated haemoglobin (HbA1c) target of <7.0% (53 mmol/mol) without significant hypoglycaemia is recommended. 4 In some individuals without concurrent serious illness and at low hypoglycaemic risk, more stringent goals may be recommended if they can safely be achieved without hypoglycaemia. 3 , 4 Additionally, body weight reduction of greater than 5% may further improve glycaemia and other cardiovascular risk factors in people with overweight or obesity, whereas maintaining >10% body weight reduction may result in possible temporary regression of T2D and improve long‐term cardiovascular outcomes and mortality. 5

Elevated HbA1c values can be improved by weight loss. In a recent retrospective, longitudinal cohort study, modest and sustained body weight reduction resulted in clinically meaningful improvements in glycaemic and metabolic parameters among people with T2D. 6 In people without T2D, baseline body mass index (BMI) and fluctuation of body weight were associated with an increased risk for T2D, irrespective of normal glucose tolerance at baseline. 7 , 8 , 9 , 10 , 11 Therefore, not only achieving but sustaining glycaemic control and body weight reduction are beneficial and important for people with T2D. 12 , 13

Tirzepatide is a glucose‐dependent insulinotropic polypeptide receptor and glucagon‐like peptide‐1 (GLP‐1) receptor agonist administered once weekly that is approved for the treatment of T2D and obesity. In the completed SURPASS clinical trials for T2D, treatment with tirzepatide (5, 10 or 15 mg) was associated with clinically meaningful reductions in HbA1c, with 81%–97% and 66%–95% of participants achieving HbA1c targets of <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol), respectively, and 54%–88% of participants achieving ≥5% body weight reduction at the primary endpoints of 40 or 52 weeks. 14 , 15 , 16 , 17 , 18 Specifically, in SURPASS‐2, greater mean changes from baseline in HbA1c and body weight in adults with T2D were observed with tirzepatide at all doses studied compared with once‐weekly GLP‐1 receptor agonist semaglutide 1 mg. 15

This participant‐level exploratory analysis assessed continuous time spent in glycaemic control (HbA1c <7.0% [53 mmol/mol] and ≤6.5% [48 mmol/mol] and fasting serum glucose [FSG] ≤125 mg/dL [7 mmol/L]) and continuous time spent with ≥5% body weight reduction during treatment with tirzepatide versus comparators in participants with T2D throughout the duration of each SURPASS 1–5 trial. Additional analysis assessed composite continuous time spent with sustained HbA1c ≤ 6.5% (48 mmol/mol) with ≥5% body weight reduction between tirzepatide and semaglutide 1 mg in SURPASS‐2.

2. METHODS

2.1. Study design

The study designs, background medications, full inclusion and exclusion criteria and primary results of the SURPASS 1–5 trials have been previously reported. 14 , 15 , 16 , 17 , 18 Briefly, the Phase 3 SURPASS clinical programme consisted of randomized controlled clinical studies, ranging from 40 to 104 weeks in duration and designed to assess tirzepatide 5 mg, 10 mg and 15 mg in adults with T2D. The primary measure was the mean change from baseline in HbA1c at the primary endpoints of 40 or 52 weeks, depending on the individual trial, with superiority of tirzepatide versus placebo or non‐inferiority of tirzepatide versus active comparators (semaglutide 1 mg, insulin degludec or insulin glargine). The SURPASS clinical trials did not include any specific recommendations regarding diet and exercise beyond the usual practices at each study centre; concomitant pharmacotherapy that promoted body weight reduction was not allowed.

The SURPASS clinical trials assessed in this analysis were conducted in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice and the Declaration of Helsinki. All participants provided signed informed consent, and protocols were approved by local ethical review boards.

2.2. Outcomes

This post hoc analysis evaluated continuous time spent with glycaemic control and body weight reduction, respectively, in participants with T2D randomized to tirzepatide versus comparators in the SURPASS 1–5 trials. The proportions of participants achieving glycaemic control and body weight reduction, respectively, at any time points during the primary treatment period as well as at the end of the primary treatment period were also summarized. Glycaemic control was defined as achieving and maintaining HbA1c <7.0% (53 mmol/mol) or ≤6.5% (48 mmol/mol) at each visit during treatment. Time spent maintaining FSG ≤125 mg/dL (7 mmol/L) was also assessed. Blood samples were collected and analysed via a central laboratory at least every 4 weeks for the first 24 weeks, at the primary endpoint of each study, and at one additional time point between Week 24 and the primary endpoint for SURPASS‐1, ‐3 and ‐4. Furthermore, body weight reduction control was defined as achieving and maintaining ≥5% body weight reduction. Body weight measurements were collected every 4 weeks through Week 24 and then approximately every 8–12 weeks until the primary endpoint at Week 40 or 52.

For the composite endpoint of continuous time spent in glycaemic control with sustained body weight reduction in SURPASS‐2, glycaemic control was defined as HbA1c ≤6.5% (48 mmol/mol) and weight control was defined as ≥5% body weight reduction from baseline.

2.3. Statistical analyses

Each SURPASS trial was analysed separately using data at the primary endpoints of 40 or 52 weeks, due to differences in design and background therapy. This post hoc analysis included all randomized participants from the modified intent‐to‐treat population who took at least 1 dose of the study drug. Data from participants who discontinued the study drug due to inadvertent enrolment as well as data after initiating rescue antihyperglycaemic medication or prematurely stopping the study drug (last dose date plus 7 days) were excluded (defined as the efficacy analysis set). The duration of time maintaining target was assessed based on HbA1c, FSG and body weight curves using all available visits and linear interpolation between consecutive visits. The longest duration in control for each participant was used in the analysis. Non‐parametric analysis (Wilcoxon rank sum test) was used to compare the median duration of continuous time spent in glycaemic control and body weight reduction control. Logistic regression was used to analyse the proportion of participants achieving glycaemic control and body weight reduction at any time points or at the end of the primary study period. The proportions of participants maintaining glycaemic control and body weight reduction by different percentages of treatment duration (0%–25%, 25%–50%, 50%–75% and 75%–100%) were summarized descriptively. Missing endpoint measures were imputed by predictions based on a mixed model for repeated measures using observed data in the efficacy analysis set from the same treatment group.

All analyses presented are exploratory in nature, and a p‐value <0.05 was considered statistically significant. Analyses were performed using SAS version 9.4 (Copyright © 2017 SAS Institute Inc., Cary, NC, USA).

3. RESULTS

A total of 6246 participants with T2D who received at least 1 dose of the study drug were included in this post hoc analysis (tirzepatide 5 mg, N = 1393; tirzepatide 10 mg, N = 1394; tirzepatide 15 mg, N = 1402; semaglutide 1 mg, N = 468; insulin degludec, N = 359; insulin glargine, N = 998; placebo, N = 232) (Figure S1). Baseline demographics and clinical characteristics are published and were similar across treatment arms within each trial. 17 , 18 , 19 , 20 , 21 Briefly, the mean age of randomized participants from SURPASS 1–5 ranged from 54 to 64 years, 38%–53% were female and 36%–91% were White, with a mean duration of diabetes ranging from 5 to 13 years (Table S1). A summary of treatment discontinuation rates from each trial is provided in Table S2.

3.1. Time spent in glycaemic control during the treatment period

Participants treated with tirzepatide 5, 10 or 15 mg spent longer continuous time with HbA1c <7.0% (53 mmol/mol) than comparators (p < 0.001) (Figure 1A). In studies of 40 weeks' duration (i.e., SURPASS‐1, SURPASS‐2 and SURPASS‐5), median time spent with HbA1c <7.0% (53 mmol/mol) was 32 weeks (80% of the total study duration) with tirzepatide compared with 28 weeks (70% of the total study duration) with semaglutide 1 mg and 0 weeks (0% of the total study duration) with placebo. In studies of 52 weeks' duration (i.e., SURPASS‐3 and SURPASS‐4), the median time spent with HbA1c <7.0% (53 mmol/mol) was 40–44 weeks (77%–85% of the total study duration) with tirzepatide compared with 32 weeks (62% of the total study duration) with insulin degludec and 12 weeks (23% of the total study duration) with insulin glargine. Overall, 92%–98% of participants treated with tirzepatide versus 34%–89% with active comparators or placebo achieved an HbA1c <7% at any time and 81%–97% versus 20%–81%, respectively, achieved the target at the primary endpoint (Figure 1A). Additionally, participants treated with tirzepatide 5, 10 or 15 mg spent longer continuous time with HbA1c ≤6.5% (48 mmol/mol) than comparators (p < 0.001) (Figure 1B). In studies of 40 weeks' duration, median time spent with HbA1c ≤ 6.5% (48 mmol/mol) was 28–32 weeks (70%–80%) with tirzepatide compared with 24 weeks (60%) with semaglutide 1 mg and 0 weeks (0%) with placebo. In studies of 52 weeks' duration, the median time spent with HbA1c ≤6.5% (48 mmol/mol) was 36–40 weeks (69%–77%) with tirzepatide compared with 8 weeks (15%) with insulin degludec and 0 weeks (0%) with insulin glargine. Overall, 80%–98% of participants treated with tirzepatide versus 18%–77% with active comparators or placebo achieved an HbA1c ≤6.5% at any time and 66%–95% versus 10%–66%, respectively, achieved the target at the primary endpoint (Figure 1B). Furthermore, participants treated with tirzepatide 5 mg, 10 mg or 15 mg spent longer continuous time with FSG ≤125 mg/dL (7 mmol/L) than placebo and semaglutide 1 mg (p < 0.05) (Figure 1C). In studies of 40 weeks' duration, median duration of continuous time spent with FSG ≤125 mg/dL (7 mmol/L) ranged from 24 to 32 weeks (60%–80%) with tirzepatide compared with 20 weeks (50%) with semaglutide 1 mg and 0–16 weeks (0%–40%) with placebo. In studies of 52 weeks' duration, the median duration of continuous time spent with FSG ≤125 mg/dL (7 mmol/L) ranged from 20 to 36 weeks (38%–69%) with tirzepatide compared with 36 weeks (69%) with insulin degludec and 28 weeks (54%) with insulin glargine. Overall, 86%–99% of participants treated with tirzepatide versus 46%–95% with active comparators or placebo achieved an FSG ≤125 mg/dL at any time and 64%–96% versus 16%–69%, respectively, achieved the target at the primary endpoint (Figure 1C). The proportion of participants maintaining HbA1c <7.0% (53 mmol/mol), HbA1c ≤ 6.5% (48 mmol/mol) and FSG ≤125 mg/dL (7 mmol/L) for different intervals during each trial is presented in Figure 2A–C. In general, this post hoc analysis found that a greater proportion of tirzepatide‐treated participants achieved and maintained HbA1c <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) for different intervals during each trial compared with placebo and active comparators.

FIGURE 1.

FIGURE 1

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Continuous time spent in glycaemic control. Continuous time spent in control is presented as median percentage of treatment duration for each study from the mITT population using the efficacy analysis set. *p < 0.05 and **p < 0.001 versus comparator. The proportions reaching target at any time or at the primary endpoint are the adjusted means from the logistic regression model. (A) Duration of time spent with HbA1c <7.0% (53 mmol/mol) during each study. (B) Duration of time spent with HbA1c ≤6.5% (48 mmol/mol) during each study. (C) Duration of time spent with FSG ≤125 mg/dL (7 mmol/L) during each study. HbA1c, glycated haemoglobin; mITT, modified intent‐to‐treat; N, number of participants in the analysis population.

FIGURE 2.

FIGURE 2

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Proportion of participants maintaining HbA1c and FSG thresholds by percentage of treatment duration of the trial. Data are percentage of participants who maintained glycaemic control threshold for different proportions of the treatment duration using the efficacy analysis set. FSG, fasting serum glucose; HbA1c, glycated haemoglobin; iDeg, insulin degludec; iGlar, insulin glargine; PBO, placebo; SEMA, semaglutide; TZP, tirzepatide.

3.2. Time spent in weight control during the treatment period

Participants treated with tirzepatide 5, 10 or 15 mg spent longer continuous time with ≥5% body weight reduction than comparators (p < 0.001) (Figure 3). In studies of 40 weeks' duration, median time spent with ≥5% body weight reduction was 8–24 weeks (20%–60%) with tirzepatide 5, 10 and 15 mg compared with 10 weeks (25%) with semaglutide 1 mg, and 0 weeks (0%) with placebo. In studies of 52 weeks' duration, median time spent with ≥5% body weight reduction was 28–40 weeks (54%–77%) with tirzepatide 5 mg, 10 mg and 15 mg; 0 weeks (0%) with insulin degludec; and 0 weeks (0%) with insulin glargine. Overall, 66%–94% of participants treated with tirzepatide versus 9%–67% with active comparators or placebo achieved body weight reduction ≥5% at any time, and 54%–88% versus 6%–58%, respectively, achieved the target at the primary endpoint (Figure 3). The proportion of participants maintaining the body weight reduction threshold of ≥5% for different intervals during each trial is presented in Figure 4. In general, this analysis found that a greater percentage of participants treated with tirzepatide achieved and maintained ≥5% body weight reduction compared with placebo and active comparators.

FIGURE 3.

FIGURE 3

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Continuous time spent with ≥5% body weight reduction. Continuous time spent in control is presented as median percentage of treatment duration for each study from the modified intent‐to‐treat (mITT) population using the efficacy analysis set. The proportions reaching target at any time or at the primary endpoint are the adjusted means from the logistic regression model. **p < 0.001 versus comparator.

FIGURE 4.

FIGURE 4

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Proportion of participants maintaining ≥5% body weight reduction threshold by percentage of treatment duration of the trial. Data are percentage of participants who maintained weight threshold for different proportions of the treatment duration using the efficacy analysis set. iDeg, insulin degludec; iGlar, insulin glargine; PBO, placebo; SEMA, semaglutide; TZP, tirzepatide.

3.3. Composite endpoint of median time spent with sustained HbA1c ≤ 6.5% (48 mmol/mol) and ≥5% body weight reduction in SURPASS‐2

Participants on all doses of tirzepatide spent longer continuous time with a composite of HbA1c ≤6.5% (48 mmol/mol) and ≥5% body weight reduction than those on semaglutide 1 mg (p < 0.001) (Figure 5A). This composite endpoint was achieved in 66%–85% of participants treated with tirzepatide 5, 10 and 15 mg compared with 54% of participants treated with semaglutide at any time during the trial, and 58%–79% versus 45%, respectively, achieved the composite endpoint at the primary endpoint. The median time spent with an HbA1c ≤6.5% (48 mmol/mol) and ≥5% body weight reduction was 14–24 weeks (35%–60%) with tirzepatide 5 mg, 10 mg and 15 mg versus 3 weeks (7%) with semaglutide. The duration of meeting these HbA1c and body weight reduction targets was greater even at the lowest dose of tirzepatide (5 mg) compared with semaglutide 1 mg and even longer at the 10 and 15‐mg doses.

FIGURE 5.

FIGURE 5

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Proportion of participants and continuous time spent with sustained glycaemic and weight control (HbA1c ≤6.5% [48 mmol/mol] and ≥5% body weight reduction) in SURPASS‐2. Data are from the mITT population using the efficacy analysis set. (A) Continuous time spent in glycaemic and weight control. Data are median percentage of treatment duration from SURPASS‐2. The proportions reaching target at any time or at the primary endpoint are the adjusted means from the logistic regression model. **p < 0.001 versus semaglutide 1 mg. For HbA1c analysis, the baseline HbA1c category was not included in the model. (B) Proportion of participants maintaining glycaemic and weight control for different intervals during SURPASS‐2. Data are percentage of participants who maintained thresholds for different proportions of the treatment duration. Similar missing value imputation was used as mentioned in part (A). HbA1c, glycated haemoglobin; mITT, modified intent‐to‐treat; MMRM, mixed model for repeated measures; SEMA, semaglutide; TZP, tirzepatide.

Furthermore, in SURPASS‐2, a greater proportion of participants treated with any dose of tirzepatide compared with semaglutide 1 mg maintained the composite of HbA1c ≤6.5% (48 mmol/mol) and ≥5% body weight reduction for different intervals during the trial (Figure 5B).

4. DISCUSSION

In the SURPASS 1–5 clinical trials, treatment with tirzepatide was consistently associated with significant and clinically meaningful reductions in HbA1c and body weight in people with T2D on various background medications. 14 , 15 , 16 , 17 , 18 This participant‐level exploratory analysis was the first to assess continuous time spent in glycaemic control and time spent with sustained body weight reduction with tirzepatide versus comparators in the SURPASS clinical trial programme. Over treatment periods of 40 and 52 weeks across the five SURPASS trials, participants treated with all doses of tirzepatide spent significantly longer time with HbA1c <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) than active comparators (i.e., semaglutide 1 mg, insulin degludec and insulin glargine) or placebo. Furthermore, participants treated with tirzepatide demonstrated longer continuous time with FSG ≤125 mg/dL (7 mmol/L) than placebo and semaglutide 1 mg. In addition to the longer time spent with glycaemic control, time spent with sustained body weight reduction of ≥5% was significantly longer in tirzepatide‐treated participants. Notably, in SURPASS‐2, tirzepatide was associated with increased time spent with the composite of sustained HbA1c ≤6.5% (48 mmol/mol) with ≥5% body weight reduction, and the duration was significantly longer compared with semaglutide 1 mg, even at the lowest tirzepatide dose of 5 mg, and increasing with dose.

According to guidelines, 1 , 2 two key pillars of T2D management are the achievement and maintenance of glycaemic and weight management goals. Across the SURPASS 1–5 trials, over 90% of all tirzepatide‐treated participants achieved a target HbA1c <7.0% (53 mmol/mol) and at least 80% achieved HbA1c ≤6.5% (48 mmol/mol) at some point during the study. As evidenced by the duration of time in control, these targets are often met early during treatment, even before escalation to higher doses is achieved, and few participants (≤15% at the 5‐mg dose and ≤7% at the 15‐mg dose) lost control by the end of each study. In SURPASS 1–4, at least 75% of participants treated with tirzepatide were able to achieve ≥5% body weight reduction, and <15% of participants on tirzepatide 5 mg and ≤6% of participants on tirzepatide 10 or 15 mg lost control by the end of each study.

Achieving and maintaining stringent, closer‐to‐normal glycaemic control and meaningful weight management goals over long periods of time may lead to long‐term benefits for people with T2D. 19 , 20 , 21 , 22 As demonstrated by both the UK Prospective Diabetes Study (UKPDS) 23 and the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC), 24 intensive glucose‐lowering, even for a limited period, can result in benefits for decades, known as the legacy effect. Additionally, the nearer to normal glucose levels that can be achieved and maintained safely result in a lower risk of the development of microvascular and macrovascular complications. The Action for Health in Diabetes (Look AHEAD) 25 and the Diabetes Remission Clinical Trial (DiRECT) 26 studies have shown that achieving and maintaining weight reduction of ≥5% also leads to benefits for people with T2D, including improvements in glycaemic control, cardiovascular risk factors, physical function and health‐related quality of life. Moreover, achieving and maintaining this weight reduction goal may reduce the risk of comorbidity onset, such as hypertension and hyperlipidaemia, or may result in a reduced medication burden in patients where these conditions are already present. Even greater degrees of weight loss generally confer greater benefits, including further metabolic benefits and the possibility of diabetes remission. Although studies evaluating the long‐term benefits of achieving and maintaining both HbA1c and weight reduction goals simultaneously have not been completed, we hypothesize some additive benefit over time. This should be further examined in long‐term trials with newer pharmacological agents, including tirzepatide, that have demonstrated the ability to safely achieve these targets.

In a similar recent post hoc analysis of the PIONEER clinical trials by Rosenstock et al., time spent in HbA1c <7.0% (53 mmol/mol) with oral semaglutide 7 and 14 mg was greater compared with empagliflozin 25 mg and sitagliptin 100 mg (median duration 15–34 weeks vs. 0–11 weeks) and comparable with subcutaneous liraglutide 1.8 mg (median duration 34 weeks vs. 37 weeks). Participants treated with oral semaglutide had a greater likelihood of achieving and maintaining HbA1c <7.0% (53 mmol/mol) versus oral comparators. 27 Furthermore, a greater proportion of participants treated with oral semaglutide achieved HbA1c <7.0% (53 mmol/mol) and body weight reduction ≥5% or ≥10% at Week 26 or Week 52 versus comparators. 28 , 29 , 30 , 31 , 32 , 33 , 34

In the SURPASS‐3 and SURPASS‐4 trials, participants randomized to insulin were titrated to a target fasting blood glucose (<90 mg/dL [5 mmol/L] and <100 mg/dL [6 mmol/L], respectively) following a treat‐to‐target algorithm. 16 , 17 Similarly, in SURPASS‐5, background insulin glargine treatment was titrated to a target fasting blood glucose of <100 mg/dL (6 mmol/L) following a treat‐to‐target algorithm. 18 Therefore, it is unsurprising that a large proportion of participants randomized to insulin and placebo in these studies were able to achieve and maintain a FSG ≤125 mg/dL (7 mmol/L). Nonetheless, an approximately equal or higher proportion of participants randomized to tirzepatide were able to achieve and maintain this target for the same or longer period in these studies. Notably, this was achieved with a significantly lower incidence of hypoglycaemia (blood glucose <54 mg/dL or severe) compared with participants randomized to insulin, ranging from 1% to 2% with tirzepatide versus 7% for insulin degludec in SURPASS‐3 and 6%–9% with tirzepatide versus 19% for insulin glargine in SURPASS‐4. 16 , 17

Limitations of this study include the post hoc analyses that are exploratory in nature. There was a relatively short duration of follow‐up in these studies (40 or 52 weeks). The visit intervals for HbA1c and weight measurements ranged from 4 to 16 weeks, which do not allow for a complete assessment of continuous achievement of these endpoints. Therefore, caution must be exercised during interpretation.

In conclusion, in this participant‐level exploratory analysis of the SURPASS clinical trial programme, treatment with tirzepatide 5, 10 and 15 mg was associated with a substantially longer continuous time in glycaemic control with HbA1c <7.0% (53 mmol/mol), HbA1c ≤6.5% (48 mmol/mol) and sustained body weight reduction of ≥5% compared with placebo and active comparators in participants with T2D. Furthermore, treatment with tirzepatide was associated with longer continuous time spent with FSG ≤125 mg/dL (7 mmol/L) compared with placebo and semaglutide. The long‐term benefits of simultaneously achieving these targets should be further examined.

AUTHOR CONTRIBUTIONS

BKB and VTT are the guarantors of this work and, as such, take responsibility for the integrity of the data and the accuracy of the data analysis. ML and PS were responsible for the statistical analyses. All authors contributed to the SURPASS studies and/or current analyses. All authors participated in the interpretation of data and critical review of the manuscript, had full access to all data in the study and approved this manuscript to be submitted for publication.

FUNDING INFORMATION

This study was supported by Eli Lilly and Company.

CONFLICT OF INTEREST STATEMENT

JR reports clinical research grants from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Pfizer and Sanofi; served on scientific advisory boards; received honorarium or consulting fees from Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharma and Zealand; and received honoraria for lectures from Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk and Sanofi during the conduct of the study. WTG has served as a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand and Merck and as a site principal investigator for multicentred clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens and Pfizer. RLB is an employee and shareholder of Eli Lilly and Company and reports research grant support from Novo Nordisk, consultancy with Boehringer Ingelheim, Eli Lilly and Company, Gila Therapeutics Inc., GSK, Novo Nordisk, Pfizer and Rhythm Pharmaceuticals. ML was a contracted employee of Eli Lilly and Company at the time of this analysis. BKB, YC, PS, CAK and VTT are 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.16337.

Supporting information

Data S1. Supporting information.

DOM-27-3223-s001.docx (213.5KB, docx)

ACKNOWLEDGEMENTS

Partial data from this study were presented at the American Diabetes Association 83rd Scientific Sessions held June 23–26, 2023, in San Diego, CA, and at the European Association for the Study of Diabetes 59th Annual Meeting held October 2–6, 2023, in Hamburg, Germany.

Bergman BK, Rosenstock J, Garvey WT, et al. Time spent in glycaemic control with sustained body weight reduction with tirzepatide: A post hoc analysis of the SURPASS clinical trial programme. Diabetes Obes Metab. 2025;27(6):3223‐3232. doi: 10.1111/dom.16337

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 United States and EU and after primary publication acceptance, whichever is later. No expiration date for 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 and 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.

Supplementary Materials

Data S1. Supporting information.

DOM-27-3223-s001.docx (213.5KB, docx)

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 United States and EU and after primary publication acceptance, whichever is later. No expiration date for 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 and 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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