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Cited by 97Pharmacology and Obesity TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and Management

Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis

Open access
Hankosky, Emily R., Wang, Hui, Neff, Lisa M., Kan, Hong, Wang, Fangyu, Ahmad, Nadia N., Griffin, Ryan, Stefanski, Adam +1 more·2024·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.15318
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Abstract

Aim: To assess the effect of tirzepatide on long‐term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT‐1. Materials and Methods: SURMOUNT‐1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m 2 and at least one weight‐related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10‐year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT‐1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. Results: Tirzepatide‐treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%–1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (−23.5% to −16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate‐to‐high baseline risk was significantly greater for tirzepatide ( P < 0.05). Intermediate‐to‐high‐risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. Conclusion: Tirzepatide treatment significantly reduced the 10‐year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.

AI snapshot

Written from the paper’s full text.

TL;DR

In a post hoc analysis of SURMOUNT-1, tirzepatide significantly reduced the 10-year predicted risk of ASCVD versus placebo in adults with obesity or overweight without diabetes. Greater absolute risk reduction was seen in participants with intermediate-to-high ASCVD risk at baseline.

Key findings

  • Among 2461 participants without a history of ASCVD, baseline median 10-year predicted ASCVD risk was low and similar across groups (1.5%–1.6%). Relative change from baseline to week 72 was −23.5% to −16.4% with tirzepatide versus +12.7% with placebo (P < 0.001).
  • In the intermediate-to-high baseline risk subgroup (risk score ≥7.5%; N = 244), week 72 relative changes were −10.3%, −20.6%, and −16.1% for tirzepatide 5, 10, and 15 mg, respectively, versus +6.4% for placebo (P < 0.05).
  • More tirzepatide-treated participants improved ASCVD risk category: at week 24, 6.9% versus 2.9% with placebo (OR 2.2, 95% CI 1.6–3.0; P < 0.001); at week 72, 7.3% versus 3.1% (OR 2.4, 95% CI 1.7–3.5; P < 0.001). In the intermediate-to-high risk subgroup, improvement was 31.5% versus 13.3% at week 24 (OR 2.8, 95% CI 1.4–5.6; P = 0.003) and 31.9% versus 12.8% at week 72 (OR 2.9, 95% CI 1.3–6.2; P = 0.008).
  • Tirzepatide also improved cardiometabolic risk factors over 72 weeks, including waist circumference, SBP, DBP, fasting serum glucose, HbA1c, triglycerides, LDL cholesterol, and non-HDL cholesterol, with HDL increases demonstrated at week 72.

Methods

  • Post hoc analysis of SURMOUNT-1, a phase 3, randomized, double-blind, placebo-controlled trial in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related complication, excluding diabetes. Participants were randomized 1:1:1:1 to tirzepatide 5, 10, or 15 mg or placebo subcutaneously once weekly for 72 weeks plus lifestyle intervention.
  • The ASCVD risk analysis included 2461 participants without a lifetime history of CVD events at baseline; 78 participants (3.1%) with previous CVD event history were excluded. Mean (SD) age was 44.5 (12.3) years, mean BMI was 38.0 (6.8) kg/m², and 68.4% were female.
  • The 2013 ACC/AHA risk engine calculated 10-year predicted ASCVD risk at baseline, week 24, and week 72. Percent change in risk scores was compared using mixed model for repeated measures; risk category shifts were analyzed with repeated-measure ordinal logistic regression. Sensitivity analyses restricted to ages 40–79 years and excluded participants with CVD events during treatment.

Limitations

  • The paper states that post hoc analyses have intrinsic limitations; the ACC/AHA risk engine was not developed or validated exclusively in populations with obesity or overweight, and predicted risk needs confirmation against hard outcomes in a randomized trial.
  • The paper notes that FDA recommends a minimum of 2 years (104 weeks) for a cardiovascular outcomes trial, whereas SURMOUNT-1 lasted 72 weeks; 95% of participants had obesity (BMI ≥30 kg/m²); and the population had a low baseline ASCVD risk profile, so absolute risk changes were generally small, though this was partially addressed by the intermediate-to-high risk subgroup.
  • Evident from the text: missing predictors were not imputed, and risk scores were missing for 232 participants (9.4%) at week 24 and 497 (20.2%) at week 72, primarily due to treatment discontinuation or rescue therapy, with more missing data in the placebo group.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/dom.15318

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 25 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    All tirzepatide treatment groups demonstrated significantly greater relative reduction in ASCVD predicted risk compared with placebo when stratified by BMI or by prediabetes status.

    “Similar to the primary analysis, all tirzepatide treatment groups demonstrated significantly greater relative reduction in ASCVD predicted risk compared with placebo when stratified by BMI or by prediabetes status (Supplementary Figure S1).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.
  • Findingown data

    Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.

    “Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.”
    • Also stated in: § 3.3 | Ten-year predicted risk of ASCVD subgroup and sensitivity analyses · plain
      “Overall, treatment with tirzepatide significantly reduced the 10-year predicted risk of ASCVD compared with placebo in people with obesity or overweight but without diabetes.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.
  • Findingown data

    Relative change in predicted ASCVD risk among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide than placebo (P < 0.05).

    “Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.
  • Findingown data

    Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks.

    “Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks.”
    Quote in the paperSubstantial claim
  • Findingown data

    A total of 244 participants were considered to have intermediate-to-high risk for ASCVD (risk score ≥7.5%) at baseline.

    “A total of 244 participants were considered to have intermediate-to-high risk for ASCVD (risk score ≥7.5%) at baseline.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 27

  • May combine two claims.

    Findingown data

    In SURMOUNT-1 participants without a history of ASCVD (N = 2461), the baseline median 10-year ASCVD risk score was low and did not differ across treatment groups (1.5%-1.6%).

    “In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%-1.6%).”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Of the 2461 participants included in the ASCVD risk analysis, 622 were in placebo, 614 tirzepatide 5 mg, 616 tirzepatide 10 mg, and 609 tirzepatide 15 mg.

    “Of the 2461 participants included in this analysis, 622 were included in the placebo group, 614 were treated with tirzepatide 5 mg, 616 with tirzepatide 10 mg, and 609 with tirzepatide 15 mg.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Relative change in predicted 10-year ASCVD risk from baseline to week 72 was greater for tirzepatide (-23.5% to -16.4%) than placebo (12.7%) in participants without history of ASCVD, P < 0.001.

    “Relative change in risk from baseline to week 72 was greater for tirzepatide (À23.5% to À16.4%) than placebo (12.7%;P < 0.001).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.

  • May combine two claims.

    Findingown data

    Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population.

    “Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.

  • Classified as probably not a substantial claim.

    Findingown data

    Among 2539 SURMOUNT-1 mITT participants, 78 (3.1%) had previous CVD event history at baseline and were excluded from ASCVD predicted risk analyses.

    “Among the 2539 SURMOUNT-1 mITT participants, 78 participants (3.1%) had previous CVD event history at baseline and were excluded from ASCVD predicted risk analyses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In a sensitivity analysis restricted to participants aged 40 to 79 years, 892 (35.1%) of mITT participants aged <40 or >79 years were excluded.

    “For the first sensitivity analysis, only participants aged between 40 and 79 years were included; 892 (35.1%) of mITT participants aged <40 or >79 years were excluded from the analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    With tirzepatide treatment, there was a significantly greater relative reduction in risk for the intermediate-to-high-risk ASCVD group compared with placebo (p < 0.05), consistent with the primary overall analysis.

    “With tirzepatide treatment, there was a significantly greater relative reduction in risk for the intermediate-to-highrisk ASCVD group compared with placebo ( p < 0.05), consistent with the primary overall analysis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Compared with placebo, decreases in waist circumference, SBP and DBP from baseline were observed in all three tirzepatide treatment arms (5, 10 or 15 mg/wk) as early as week 4 and continued until week 72.

    “Compared with placebo, decreases in waist circumference, SBP and DBP from baseline were observed in all three tirzepatide treatment arms (5, 10 or 15 mg/wk) as early as week 4 and continued until week 72 (Figure 1A,C,D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Improvements in serum lipids were observed by 24 weeks and maintained until 72 weeks including reductions in LDL and non-HDL cholesterol, while increases in HDL were only demonstrated at the 72-week time point.

    “Improvements in serum lipids were observed by 24 weeks and maintained until 72 weeks including reductions in LDL and non-HDL cholesterol (Figure 1H,F), while increases in HDL were only demonstrated at the 72-week time point (Figure 1G).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    While the study focused on both people with obesity and overweight, 95% of the participants had obesity (BMI ≥30 kg/m2).

    “Furthermore, while the study focused on both people with obesity and overweight, 95% of the participants had obesity (BMI ≥30 kg/m 2 ).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The SURMOUNT-1 patient population had a low ASCVD risk profile at baseline, indicating a relatively healthy CVD risk profile, and hence the absolute change in the predicted ASCVD risk score was generally small.

    “Finally, the SURMOUNT-1 patient population had a low ASCVD risk profile at baseline, indicating a relatively healthy CVD risk profile in this population, and hence the absolute change in the predicted ASCVD risk score was generally small.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The placebo group tended to have more missing data than the tirzepatide groups, consistent with greater treatment and study discontinuation in the placebo group.

    “The placebo group tended to have more missing data than the tirzepatide groups, consistent with greater treatment and study discontinuation in the placebo group in the SURMOUNT-1 study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At week 24, 6.9% of participants treated with tirzepatide and 2.9% in the placebo group had improved ASCVD risk profiles, indicating that participants treated with tirzepatide had 2.2 times greater odds (95% CI 1.6, 3.0; P < 0.001) of improving their risk score category from baseline to week 24 than placebo-treated participants.

    “At week 24 , 6 . 9% of participants treated with tirzepatide and 2.9% in the placebo group had improved ASCVD risk profiles, indicating that participants treated with tirzepatide had 2.2 times greater odds (95% confidence interval [CI] 1.6, 3.0; P < 0.001) of improving their risk score category from baseline to week 24 than placebo-treated participants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The majority of patients (80.4%) were in the low-risk group (risk score <5%), 8.6% of patients were in the borderline-risk group (risk score ≥5% and <7.5%), 10.0% of patients were in the intermediate-risk group (risk score ≥7.5% and <20%), and only 1.0% patients were in the high-risk group (risk score ≥20%).

    “The majority of patients (80.4%) were in the low-risk group (risk score <5%), 8.6% of patients were in the borderline-risk group (risk score ≥5% and <7.5%), 10.0% of patients were in the intermediate-risk group (risk score ≥7.5% and <20%), and only 1.0% patients were in the high-risk group (risk score ≥20%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The baseline median 10-year ASCVD predicted risk scores ranged from 1.5% to 1.6%, with no difference among the four treatment groups.

    “The baseline median 10-year ASCVD predicted risk scores ranged from 1.5% to 1.6%, with no difference among the four treatment groups (Figure2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The median risk scores for tirzepatide 5, 10, 15 mg and placebo groups were 1.4%, 1.2%, 1.3% and 1.6% at week 24, and 1.3%, 1.2%, 1.1% and 1.7% at week 72, respectively.

    “The median risk scores for tirzepatide 5, 10, 15 mg and placebo groups were 1.4%, 1.2%, 1.3% and 1.6% at week 24, and 1.3%, 1.2%, 1.1% and 1.7% at week 72, respectively.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In SURMOUNT-1, the adverse event of T2D was reported in five participants (four in placebo, one in tirzepatide).

    “Throughout the 72-week study period, the adverse event of T2D was reported in five participants (four in the placebo group, and one in the tirzepatide group).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At week 72, 7.3% of participants treated with tirzepatide and 3.1% in the placebo group had improved ASCVD risk profiles; participants treated with tirzepatide had 2.4 times greater odds (95% CI 1.7, 3.5; P < 0.001) of improving their risk score category from baseline to week 72 than those in the placebo group.

    “Similarly, at week 72, 7.3% of participants treated with tirzepatide and 3.1% in the placebo group had improved ASCVD risk profiles; participants treated with tirzepatide had 2.4 times greater odds (95% CI 1.7, 3.5; P < 0.001) of improving their risk score category from baseline to week 72 than those in the placebo group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Tirzepatide has previously shown significant HbA1c and weight reduction in the SURPASS clinical trial programme in adults with T2D, without any indication of an increase in the risk of major cardiovascular events.

    “Tirzepatide has previously shown significant glycated haemoglobin (HbA1c) and weight reduction in the SURPASS clinical trial programme in adults with T2D, [21][22][23][24][25] without any indication of an increase in the risk of major cardiovascular events.25,26”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21][22][23][24][25]

      Not checked in the free run.

    • cites [25] source

      Not checked in the free run.

    • cites [26] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Tirzepatide reduces the risk of ASCVD, irrespective of baseline BMI or prediabetes status.

    “reduces the risk of ASCVD, irrespective of baseline BMI or prediabetes status.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The cardiometabolic outcome variables were assumed to remain constant throughout the study period.

  • Classified as probably not a substantial claim.

    Premisecitation

    Combining GLP-1 and GIP receptor agonism has the potential to enhance the weight-loss effects seen with GLP-1 receptor agonism alone.

    “combining GLP-1 and GIP receptor agonism has the potential to enhance the weight-loss effects seen with GLP-1 receptor agonism alone.19,20”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] source

      Not checked in the free run.

    • cites [20] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Commercially available GLP-1 receptor agonists have demonstrated improvements in major adverse cardiovascular events in patients with T2D.

    “In addition, commercially available GLP-1 receptor agonists have demonstrated improvements in major adverse cardiovascular events in patients with T2D.18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Effective obesity treatments may reduce obesity-related morbidity and mortality, including ASCVD and CVD mortality.

    “Effective obesity treatments may reduce obesity-related morbidity and mortality, including atherosclerotic CVD (ASCVD) and CVD mortality.3,5,9”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] source

      Not checked in the free run.

    • cites [5] source

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    • cites [9] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Long-acting GLP-1 receptor agonists have demonstrated improvements in CVD risk factors including waist circumference, SBP, triglycerides, HDL cholesterol, and LDL in individuals with obesity.

    “Long-acting glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated promising weight reduction in recent studies, 14,15 together with improvements in CVD risk factors including waist circumference, systolic blood pressure (SBP), triglycerides, high-density lipoprotein (HDL) cholesterol, and lowdensity lipoprotein (LDL) in individuals with obesity.16,17”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [14] source

      Not checked in the free run.

    • cites [15] source

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    • cites [16] source

      Not checked in the free run.

    • cites [17] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Sensitivity analysis 1 was conducted among participants aged ≥40 to ≤79 years at baseline to reflect the population in which the ACC/AHA risk engine was developed.

    “Sensitivity analysis 1 was conducted among participants aged ≥40 to ≤79 years at baseline to reflect the population in which the ACC/AHA risk engine was developed.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The ASCVD predicted risk was calculated using a risk engine developed by the ACC/AHA in 2013.

    “The ASCVD predicted risk was calculated using a risk engine developed by the ACC/AHA in 2013.28,29”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [28] source

      Not checked in the free run.

    • cites [29]

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The improvement in the ASCVD risk score was accompanied by significant improvements in multiple cardiometabolic risk factors (waist circumference, blood pressure, fasting glucose, HbA1c, and lipid levels) in the full SURMOUNT-1 population.

    “The improvement in the ASCVD risk score was accompanied by significant improvements in multiple cardiometabolic risk factors (waist circumference, blood pressure, fasting glucose, HbA1c, and lipid levels) in the full SURMOUNT-1 population.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A small retrospective study demonstrated a significant decrease in predicted ASCVD risk between baseline and 1 year after initiating semaglutide treatment.

    “In contrast, the results of a small retrospective study demonstrated a significant decrease in predicted ASCVD risk between baseline and 1 year after initiating semaglutide treatment.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The ACC/AHA model was selected over the Framingham model due to its broader generalizability across populations.

    “The ACC/AHA model was selected over the Framingham model due to its broader generalizability across populations.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    The ACC/AHA risk engine is intended for the prediction of primary CVD events.

    “This was consistent with the intended use of the ACC/AHA risk engine for the prediction of primary CVD events.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Sensitivity analyses evaluated the robustness of the primary analysis choice.

    “Sensitivity analyses evaluated the robustness of this methodological choice.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a phase 3 study investigating semaglutide for weight loss in patients with obesity or overweight, participants who received semaglutide demonstrated improvements in cardiometabolic risk factors.

    “In a phase 3 study investigating the effect of semaglutide, a GLP-1 receptor agonist, on weight loss in patients with obesity or overweight, participants who received semaglutide demonstrated improvements in cardiometabolic risk factors.15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The risk engine calculates the predicted risk of ASCVD but needs to be confirmed with a randomized trial against hard outcomes.

    “Additionally, the risk engine calculates the predicted risk of ASCVD but needs to be confirmed with a randomized trial against hard outcomes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Sensitivity analysis 2 excluded participants who experienced a CVD event postbaseline.

    “Sensitivity analysis 2 excluded participants who experienced a CVD event postbaseline.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The ACC/AHA risk engine was not developed or validated in populations of people with obesity or overweight exclusively, but the validation cohorts did include large, diverse populations.

    “The ACC/AHA risk engine was not developed or validated in populations of people with obesity or overweight exclusively, but the validation cohorts did include large, diverse populations.29”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Missing predictors were not imputed; risk scores for participants with missing predictors were not calculated.

    “Missing predictors were not imputed.Risk scores for participants with missing predictors were not calculated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Protocols were approved by independent ethics committees or institutional review boards.

    “Protocols were approved by independent ethics committees or institutional review boards.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The duration of the SURMOUNT-1 trial was 72 weeks.

    “The duration of the SURMOUNT-1 trial was 72 weeks.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a large phase 3 study (SELECT), patients with obesity or overweight without T2D treated with semaglutide demonstrated a 20% reduction in the risk of major adverse cardiovascular events compared with placebo.

    “The effects of semaglutide on cardiovascular outcomes in people with obesity or overweight without T2D were assessed in a large phase 3 study; patients treated with semaglutide demonstrated a 20% reduction in the risk of major adverse cardiovascular events compared with placebo (SELECT; NCT03574597).33”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    More participants' ASCVD risk categories improved and fewer worsened at weeks 24 and 72 with tirzepatide compared to placebo.

    “Specifically, more participants' ASCVD risk categories improved and fewer worsened at weeks 24 and 72 with tirzepatide compared to placebo.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The consistency of results from the primary, subgroup, and sensitivity analyses indicates that the data are robust.

    “Finally, the consistency of results from the primary, subgroup, and sensitivity analyses indicates that the data are robust.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    The original study participant consent covered the analyses conducted in the present study.

    “The original study participant consent covered the analyses conducted in the present study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The analysis included a large, global sample size originally recruited for the SURMOUNT-1 trial, which further increased the generalizability of these results.

    “Second, the analysis included a large, global sample size originally recruited for the SURMOUNT-1 trial, which further increased the generalizability of these results.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    To our knowledge, this is the first analysis aimed at evaluating the effects of tirzepatide on long-term ASCVD risk in people with obesity or overweight.

    “To our knowledge, this is the first analysis aimed at evaluating the effects of tirzepatide on long-term ASCVD risk in people with obesity or overweight.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The effect of tirzepatide on long-term risk of ASCVD in people with obesity or overweight is unknown.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The primary analysis was performed among all participants free of CVD at baseline without consideration for CVD events that occurred during the study.

    “The primary analysis was performed among all participants free of CVD at baseline without consideration for CVD events that occurred during the study.”
    Quote in the paperSubstantial claim
45 of 45

  • The paper relies on this without support.

    The effect of tirzepatide on long-term risk of ASCVD in people with obesity or overweight is unknown.

    “Although the improvements in cardiovascular risk factors in SURMOUNT-1 are promising, the effect of tirzepatide on the longterm risk of ASCVD in people with obesity or overweight is still unknown.”

  • The authors state this as an assumption.

    The cardiometabolic outcome variables were assumed to remain constant throughout the study period.

    “The cardiometabolic outcome variables were measured at various baseline and assumed to remain constant throughout the study period.”

  • The authors state this as an assumption.

    The odds ratios of tirzepatide versus placebo were assumed to be the same for the outcome of improved ASCVD risk profile relative to maintaining a stable ASCVD risk profile and for the outcome of stable ASCVD risk profile relative to the worsened risk profile.

    “The odds ratios of tirzepatide versus placebo were assumed to be the same for the outcome of improved ASCVD risk profile relative to maintaining a stable ASCVD risk profile and for the outcome of stable ASCVD risk profile relative to the worsened risk profile.”

  • The paper relies on this without support.

    The ACC/AHA risk engine is intended for the prediction of primary CVD events.

    “This was consistent with the intended use of the ACC/AHA risk engine for the prediction of primary CVD events.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Little is known about the effect of tirzepatide on a range of nontraditional biomarkers associated with cardiovascular disease, beyond its effects on lipids and blood pressure.

    “Little is known about the effect of tirzepatide on a range of nontraditional biomarkers associated with cardiovascular disease, beyond its effects on lipids and blood pressure. 11”

    From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [11]

    The cardiometabolic-endpoints passage (section 3.3; page unavailable) documents tirzepatide’s effects on lipids and blood pressure. The Introduction says its effect on long-term ASCVD risk was unknown, but does not make the distinct claim that little is known about a range of nontraditional cardiovascular biomarkers. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Tirzepatide reduces 10-year ASCVD risk and improves blood pressure, lipids, and inflammation in people without diabetes.

    “Though CVOT data are pending, post hoc SURMOUNT-1 analyses showed reduced 10-year ASCVD risk and improved blood pressure, lipids, and inflammation in participants without diabetes [10].”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [10]

    The Abstract reports a reduction in 10-year *predicted* ASCVD risk in participants with obesity or overweight without diabetes. Section 3.3 reports improvements in blood pressure and lipids, but the paper’s listed cardiometabolic outcomes do not include inflammation; the citation does not support that part of the claim. The risk finding concerns a prediction, not observed 10-year cardiovascular events. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting baseline intermediate-to-high-risk counts

    Minor

    The text reports 244 participants with intermediate-to-high ASCVD risk at baseline, but Table 1 lists 247 at intermediate risk and 25 at high risk, totaling 272.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Ghusn W, 2023, Cardiovascular risk improvement with semaglutide in patients with overweight and obesity: a multi‐centered study, Obes Facts, 16, 352

Cited by

Sorted by citations

Related

Authors
Hankosky, E. R., Wang, H., Neff, L. M., Kan, H., Wang, F., Ahmad, N. N., Griffin, R., Stefanski, A., & Garvey, W. T.
Affiliations
  • Eli Lilly (United States) (US)
  • TechData Services Company King of Prussia Pennsylvania USA
  • Eli Lilly and Company Indianapolis Indiana USA
  • University of Alabama at Birmingham (US)
Corresponding author
Garvey, W. Timothy
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2023-11-06
Volume
26
Issue
1
Pages
319-328
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.15318
OpenAlex
W4388440956
Semantic Scholar
c21857ca79db64fa69361cdf2700570268f24cb8
Cited by
97
References
30
Citations by year
2026: 22 · 2025: 50 · 2024: 25
FWCI
15.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Eli Lilly and Company
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
tirzepatide, atherosclerotic cardiovascular disease, obesity, overweight, cardiometabolic risk factors, GLP-1 receptor agonists
MeSH terms
Cardiometabolic Risk Factors, Tirzepatide, Adult, Cardiovascular Diseases, Diabetes Mellitus, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Obesity, Overweight, Atherosclerosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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