The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index; 15 of the 32 sources its claims cite were checked for support.
Outcomes in patients with diabetes, atherosclerotic cardiovascular disease, and heart failure treated with tirzepatide or dulaglutide: SURPASS-CVOT analysis
Open accessAbstract
Aims: The impact of tirzepatide and dulaglutide on major adverse cardiovascular events (MACE) and heart failure (HF) outcomes according to HF status is unknown. Methods and results: Patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease were treated with tirzepatide up to 15 mg or dulaglutide 1.5 mg weekly (average 4 years). The incidence of MACE-3 [cardiovascular (CV) death, myocardial infarction (MI), stroke], MACE-4 (CV death, MI, stroke, coronary revascularization) and composite of all-cause or CV death and hospitalization or urgent visits for HF were analysed in patients with and without a history of HF. A history of HF (20.3%) was associated with more coronary artery disease and prior MI. Incidences of event categories were higher in the HF group. The hazard ratio (HR) for all-cause death or hospitalization or urgent visits for HF on tirzepatide vs. dulaglutide was 0.83 [95% confidence interval (CI) 0.70–0.99] in patients with HF and 0.88 (95%CI 0.78–1.00) without HF. The HR for CV death or hospitalization or urgent visits for HF was 0.85 (95%CI 0.70–1.03) and 0.96 (95%CI 0.83–1.12), for MACE-3 0.90 (95%CI 0.76–1.08) and 0.93 (95%CI 0.83–1.04), and for MACE-4 0.81 (95%CI 0.69–0.95) and 0.91 (95%CI 0.83–1.00) in patients with and without HF, respectively. The patient-reported outcomes of APPADL and EQ-5D-5L visual analogue scores improved and were higher on tirzepatide in both groups. Conclusion: With overall non-inferiority established, this exploratory analysis revealed lower rates of the composite of all-cause death or HF events, or MACE-4 among patients with T2D and HF treated with tirzepatide compared with dulaglutide.
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TL;DR
In this prespecified exploratory analysis of SURPASS-CVOT, patients with type 2 diabetes and atherosclerotic cardiovascular disease plus a history of heart failure had higher event rates, and tirzepatide was associated with lower rates of all-cause death or HF events and MACE-4 compared with dulaglutide. The findings are hypothesis-generating because the analysis was exploratory and not adjusted for multiplicity.
Key findings
- A history of HF was present in 20.3% of patients and was associated with more coronary artery disease and prior MI, higher body weight (96.3 vs. 91.6 kg, P < 0.001), and lower eGFR (73.4 vs. 80.3 mL/min/1.73 m²) at baseline.
- For all-cause death or hospitalization/urgent visits for HF, the HR for tirzepatide vs. dulaglutide was 0.83 (95% CI 0.70–0.99) in patients with HF and 0.88 (95% CI 0.78–1.00) without HF.
- For MACE-4 (CV death, MI, stroke, or coronary revascularization), the HR was 0.81 (95% CI 0.69–0.95) with HF and 0.91 (95% CI 0.83–1.00) without HF; for MACE-3, HRs were 0.90 (95% CI 0.76–1.08) and 0.93 (95% CI 0.83–1.04), respectively.
- Tirzepatide produced greater reductions in HbA1c, body weight, and systolic blood pressure in both HF groups, and patient-reported APPADL and EQ-5D-5L visual analogue scores were higher with tirzepatide at month 48.
Methods
- SURPASS-CVOT was a Phase 3, event-driven, multicentre, international, randomized, double-blind, active-comparator trial comparing tirzepatide up to 15 mg vs. dulaglutide 1.5 mg weekly in adults with T2D and established CV disease; 13,299 patients were randomized at 640 sites across 30 countries, with average treatment duration about 4 years.
- This prespecified exploratory subgroup analysis compared patients with vs. without a history of HF at enrolment, defined by self-reported hospitalization for HF prior to screening and/or HF history on the medical history form.
- HF and MACE outcomes were analyzed using Cox proportional hazards models stratified by baseline SGLT2 inhibitor use; continuous outcomes used ANCOVA with multiple imputation, and all findings were considered exploratory without family-wise type 1 error control.
Limitations
- The paper states this was an exploratory, hypothesis-generating analysis; all P values are nominal and analyses were not adjusted for multiplicity.
- HF status was identified by self-reported clinical history; cardiac imaging and HF biomarkers such as brain natriuretic peptide were not measured, and HF phenotype (reduced vs. preserved ejection fraction) could not be determined.
- Patients with class IV HF or recent HF hospitalization were excluded, so findings do not apply to them; SURPASS-CVOT was an active-comparator trial without direct placebo comparison, and observed clinical benefits were restricted to fatal outcomes rather than HF-specific benefit.
- The paper also notes that sex, race, and geographical representation may limit generalizability, and that SGLT2 inhibitor initiation/discontinuation during the trial occurred non-randomly and requires further investigation.
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Claims the paper makes
15 of 32 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured
- Interpretationcitation
Establishing non-inferiority to dulaglutide, an agent previously shown to reduce MACE-3 risk versus placebo, confirms the cardiovascular benefits of tirzepatide compared with an imputed placebo.
“Based on the original study design, establishing non-inferiority to an agent which had previously demonstrated a reduction in MACE-3 risk compared with placebo, confirms the CV benefits of tirzepatide compared with an imputed placebo.19”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [19] Nicholls, 2024, Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics, Am Heart J source
- Rests on an assumption: The MACE-3 reduction demonstrated by dulaglutide versus placebo in prior trials is applicable to the SURPASS-CVOT population and can be used to impute placebo effects for tirzepatide.
- Premisecitation
Clinical trials have demonstrated that the benefits of GLP-1 receptor agonists on metabolic risk factors translate into a reduction in the rate of major adverse cardiovascular events in patients at high cardiovascular risk with type 2 diabetes, chronic kidney disease, or obesity.
“Clinical trials have demonstrated that the benefits of glucagonlike peptide-1 (GLP-1) receptor agonists on metabolic risk factors translate into a reduction in the rate of major adverse cardiovascular events (MACE) in patients at high cardiovascular (CV) risk with type 2 diabetes (T2D), chronic kidney disease, or obesity.[1][2][3][4][5]”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [1] Gerstein, 2019, Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial, Lancet source
- cites [2] McGuire, 2025, Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes, N Engl J Med source
- cites [3] Lincoff, 2023, Semaglutide and cardiovascular outcomes in obesity without diabetes, N Engl J Med source
The Discussion reports fewer major adverse cardiovascular events with semaglutide in patients with overweight or obesity and preexisting cardiovascular disease, and cites similar reductions in high-risk patients with type 2 diabetes. It also reports improvements in metabolic risk markers, but treats their role in causing the cardiovascular benefit as a possible mechanism, not a demonstrated link. The passages do not establish a cardiovascular-event reduction in patients with chronic kidney disease as a group. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Interpretationcitation
In individuals with type 2 diabetes, cardiovascular and heart failure benefits associated with incretin-based therapies are likely mediated only partly by intentional weight loss.
“In individuals with T2D, CV, and HF benefits associated with incretin-based therapies are likely mediated only partly by intentional weight loss.”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [16] Ussher, 2023, Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action, Nat Rev Cardiol source
- cites [17] Mullur, 2024, GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms, J Endocrinol source
The Mechanistic data and Heart failure and GLP-1RA sections discuss potential pathways for cardiovascular and heart-failure benefits beyond weight loss. But the Heart failure reported in CVOTs section says improvements in symptoms and exercise function appeared directly related to the magnitude of weight loss, while Triple agonist clinical trials says co-agonist benefits cannot yet be uncoupled from additional weight loss. The review therefore does not establish the claim across incretin-based therapies. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [18] Moiz, 2026, GLP-1 Receptor agonists and blood pressure: a state-of-the-art review of mechanisms, evidence, and clinical implications, Am J Hypertens source
The Conclusions (page unavailable) say that blood-pressure reductions can lower cardiovascular-event risk and that these benefits likely involve both weight-mediated and weight-independent mechanisms. The Heart failure section (page unavailable) reports benefits in HFpEF but does not assess how much weight loss mediates them. The review therefore supports the cardiovascular part in the context of blood-pressure effects, not the claim about both cardiovascular and heart-failure benefits in people with T2D. (LLM, conf=0.78)
Experimental — accuracy not yet measured
- Findingown data
Patients treated with tirzepatide demonstrated greater reductions in HbA1c in the presence of heart failure (-1.60 vs -0.90%, P < 0.001).
“Patients treated with tirzepatide demonstrated greater reductions in HbA1c in the presence (-1.60 vs. -0.90%,P < 0.001)”
Quote in the paperNot a substantial claim - Findingown data
A greater proportion of patients treated with dulaglutide underwent initiation of treatment with an SGLT2 inhibitor after commencement of the trial in the group without a history of heart failure (25.3% vs 15.9%, P < 0.001).
“and without (25.3% vs. 15.9%, P < 0.001) a history of HF.”
Quote in the paperNot a substantial claim
- Findingown data
In patients without a history of heart failure, the hazard ratio for all-cause death or hospitalization or urgent visits for heart failure on tirzepatide vs dulaglutide was 0.88 (95% CI 0.78-1.00).
“and 0.88 (95%CI 0.78-1.00)without HF.”
Quote in the paperNot a substantial claim - Findingown data
Tirzepatide produced a smaller reduction in eGFR in the presence of heart failure (-7.1 vs -8.0 mL/min/1.73 m2).
“and a smaller re- duction in eGFR in the presence (-7.1 vs. -8.0 mL/min/ 1.73 m 2 )”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, all-cause death occurred in 13.5% of the tirzepatide group and 16.7% of the dulaglutide group (HR 0.80, 95% CI 0.65-0.97).
“All-cause death occurred in 13.5% of the tirzepatide group and 16.7% of the dulaglutide group (HR 0.80, 95%CI 0.65-0.97) in patients with a history of HF”
Quote in the paperSubstantial claim - Findingown data
There was no difference in other clinical characteristics or baseline medication use between the treatment groups in the presence or absence of a history of heart failure.
“There was no difference in other clinical characteristics or baseline medication use between the treatment groups in the presence or absence of a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, stroke occurred in 4.4% of the tirzepatide group and 4.8% of the dulaglutide group (HR 0.89, 95% CI 0.62-1.27).
“Stroke occurred in 4.4% of the tirzepatide group and 4.8% of the dulaglutide group (HR 0.89, 95%CI 0.62-1.27) in patients with a history of HF”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, the composite of MACE-4 occurred in 20.5% of the tirzepatide group and 24.7% of the dulaglutide group (HR 0.81, 95% CI 0.69-0.95).
“The composite of CV death, myocardial infarction, stroke, or coronary revascularization (MACE-4) occurred in 20.5% of the tirzepatide group and 24.7% of the dulaglutide group (HR 0.81, 95%CI 0.69-0.95) in patients with a history of HF”
Quote in the paperSubstantial claim - Findingown data
This exploratory analysis revealed lower rates of the composite of all-cause death or heart failure events among patients with type 2 diabetes and heart failure treated with tirzepatide compared with dulaglutide.
“this exploratory analysis revealed lower rates of the composite of allcause death or HF events, or MACE-4 among patients with T2D and HF treated with tirzepatide compared with dulaglutide.”
Quote in the paperSubstantial claim - Findingown data
This exploratory analysis revealed lower rates of MACE-4 among patients with type 2 diabetes and heart failure treated with tirzepatide compared with dulaglutide.
“this exploratory analysis revealed lower rates of the composite of allcause death or HF events, or MACE-4 among patients with T2D and HF treated with tirzepatide compared with dulaglutide.”
Quote in the paperSubstantial claim - Findingown data
In patients with a history of heart failure, the hazard ratio for cardiovascular death or hospitalization or urgent visits for heart failure was 0.85 (95% CI 0.70-1.03).
“The HR for CV death or hospitalization or urgent visits for HF was 0.85 (95%CI 0.70-1.03)and 0.96 (95%CI 0.83-1.12),for MACE-3 0.90 (95%CI 0.76-1.08)and 0.93 (95%CI 0.83-1.04),and for MACE-4 0.81 (95%CI 0.69-0.95) and 0.91 (95%CI 0.83-1.00) in patients with and without HF, respectively.”
Quote in the paperSubstantial claim - Findingnone given
Participants who had heart failure before the study were more likely to have heart and blood vessel problems during the study than people without heart failure.
“Participants who had heart failure before the study were more likely to have heart and blood vessel problems during the study than people without heart failure.”
Quote in the paperNot a substantial claim - Findingown data
Incidences of event categories were higher in the heart failure group.
“Incidences of event categories were higher in the HF group.”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, cardiovascular death occurred in 4.7% of the tirzepatide group and 4.9% of the dulaglutide group (HR 0.95, 95% CI 0.80-1.13).
“and in 4.7% of the tirzepatide group and 4.9% of the dulaglutide group (HR 0.95, 95%CI 0.80-1.13) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients with high or very-high risk chronic kidney disease at baseline and a history of heart failure, the change in eGFR from baseline to 36 months was -5.2 vs -8.5 mL/min/1.73 m2 with tirzepatide vs dulaglutide, respectively (between-group difference 3.3, 95% CI 1.4-5.3).
“The change in eGFR from baseline to 36 months in patients with high or very- high risk chronic kidney disease at baseline, a prespecified sec- ondary endpoint, was -5.2 vs. -8.5 mL/min/1.73 m 2 with tirze- patide vs. dulaglutide, respectively [between group difference 3.3, 95% confidence interval (CI) 1.4-5.3] in patients with a his- tory of HF”
Quote in the paperSubstantial claim - Findingown data
In patients with a history of heart failure, hospitalization or urgent visits for heart failure occurred in 7.6% of the tirzepatide group and 7.7% of the dulaglutide group (HR 0.97, 95% CI 0.73-1.27).
“Hospitalization or urgent visits for HF occurred in 7.6% (99 patients, with a total of 159 events) of the tirzepatide group and 7.7% (105 patients, with a total of 172 events) of the dulaglutide group (HR 0.97, 95%CI 0.73-1.27) in patients with a history of HF”
Quote in the paperNot a substantial claim - Findingown data
At month 48, patients treated with tirzepatide demonstrated a greater transformed APPADL score in patients without a history of heart failure (63.3 vs 59.7 units, P < 0.001).
“and without (63.3 vs. 59.7 UNITS, P < 0.001) a history of HF compared with dulaglutide”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, the composite of cardiovascular death or hospitalization or urgent visits for heart failure occurred in 6.1% of the tirzepatide group and 6.3% of the dulaglutide group (HR 0.96, 95% CI 0.83-1.12).
“and in 6.1% of the tirzepatide group and 6.3% of the dulaglutide group (HR 0.96, 95%CI 0.83-1.12) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, cardiovascular death occurred in 8.9% of the tirzepatide group and 11.0% of the dulaglutide group (HR 0.80, 95% CI 0.63-1.02).
“CV death occurred in 8.9% of the tirzepatide group and 11.0% of the dulaglutide group (HR 0.80, 95%CI 0.63-1.02) in patients with a history of HF”
Quote in the paperSubstantial claim - Findingown data
Patients with a history of heart failure had lower eGFR at baseline (73.4 vs 80.3 mL/min/1.73m2).
“and lower eGFR (73.4 vs. 80.3 mL/min/1.73m 2 ) at baseline.”
Quote in the paperNot a substantial claim - Findingown data
Patients with a history of heart failure were less likely to discontinue study drug due to an adverse event (10.4% vs 12.0%, P = 0.02).
“but they were less likely to discontinue study drug due to an adverse event (10.4% vs. 12.0%, P = 0.02) compared with those without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, the composite of death due to any cause or hospitalization or urgent visits for heart failure occurred in 18.2% of the tirzepatide group and 21.5% of the dulaglutide group (HR 0.83, 95% CI 0.70-0.99).
“The composite of death due to any cause or hospitalization or urgent visits for HF occurred in 18.2% of the tirzepatide group and 21.5% of the dulaglutide group [hazard ratio (HR) 0.83, 95%CI 0.70-0.99] in patients with a history of HF”
Quote in the paperSubstantial claim - Findingown data
In patients with a history of heart failure, the hazard ratio for MACE-3 was 0.90 (95% CI 0.76-1.08).
“for MACE-3 0.90 (95%CI 0.76-1.08)and 0.93 (95%CI 0.83-1.04)”
Quote in the paperNot a substantial claim - Findingown data
A history of heart failure (20.3%) was associated with more coronary artery disease and prior myocardial infarction.
“A history of HF (20.3%) was associated with more coronary artery disease and prior MI.”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, the composite of MACE-3 occurred in 17.2% of the tirzepatide group and 18.7% of the dulaglutide group (HR 0.90, 95% CI 0.76-1.08).
“The composite of MACE-3 occurred in 17.2% of the tirzepatide group and 18.7% of the dulaglutide group (HR 0.90, 95%CI 0.76-1.08) in patients with a history of HF”
Quote in the paperSubstantial claim - Findingown data
In patients without a history of heart failure, the hazard ratio for MACE-3 was 0.93 (95% CI 0.83-1.04).
“for MACE-3 0.90 (95%CI 0.76-1.08)and 0.93 (95%CI 0.83-1.04)”
Quote in the paperNot a substantial claim - Findingown data
Among baseline SGLT2i users, a greater proportion of patients treated with tirzepatide discontinued SGLT2 inhibitor use after commencement of the trial in the group without a history of heart failure (19.9% vs 12.9%, P < 0.001).
“and without (19.9% vs. 12.9%, P < 0.001) a history of HF”
Quote in the paperNot a substantial claim - Findingown data
Patients treated with tirzepatide demonstrated greater reductions in body weight in the absence of heart failure (-11.7 vs -4.7%, P < 0.001).
“or absence (-11.7 vs. -4.7%,P < 0.001) of HF”
Quote in the paperNot a substantial claim - Findingown data
Patients with a history of heart failure were more likely to experience a serious adverse event (36.4% vs 30.7%, P < 0.001).
“Patients with a history of HF were more likely to experience a serious adverse event (36.4% vs. 30.7%,P < 0.001)”
Quote in the paperNot a substantial claim - Findingnone given
The clinical benefits observed in this analysis were restricted to fatal outcomes.
“The clinical benefits observed in this analysis were restricted to fatal outcomes.”
Quote in the paperSubstantial claim - Findingown data
The deterioration in quality of life was attenuated in people treated with tirzepatide.
“We observed that this deterioration in quality of life was attenuated in people treated with tirzepatide.”
Quote in the paperSubstantial claim - Findingown data
At month 48, patients treated with tirzepatide demonstrated a greater EQ-5D-5L visual analogue score in patients with a history of heart failure (72.1 vs 69.6 units, P < 0.001).
“Similarly, at month 48, patients treated with tirzepatide demonstrated a greater EQ-5D-5L visual analogue score in patients with (72.1 vs. 69.6UNITS, P < 0.001)”
Quote in the paperNot a substantial claim - Findingown data
Tirzepatide produced a greater reduction in systolic blood pressure in the presence of heart failure (-6.0 vs -3.8 mmHg, P < 0.001).
“Tirzepatide produced a greater reduction in systolic blood pressure in the presence (-6.0 vs. -3.8 mmHg, P < 0.001)”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, hospitalization or urgent visits for heart failure occurred in 1.9% of the tirzepatide group and 1.9% of the dulaglutide group (HR 0.98, 95% CI 0.74-1.30).
“and in 1.9% (99 patients, with a total of 131 events) of the tirzepatide group and 1.9% of the dulaglutide group (99 patients, with a total of 146 events) (HR 0.98, 95%CI 0.74-1.30) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, myocardial infarction occurred in 6.0% of the tirzepatide group and 5.9% of the dulaglutide group (HR 0.99, 95% CI 0.73-1.36).
“Myocardial infarction occurred in 6.0% of the tirzepatide group and 5.9% of the dulaglutide group (HR 0.99, 95%CI 0.73-1.36) in patients with a history of HF”
Quote in the paperNot a substantial claim - Findingown data
Tirzepatide produced a greater reduction in systolic blood pressure in the absence of heart failure (-6.2 vs -4.2 mmHg, P < 0.001).
“or absence (-6.2 vs. -4.2 mmHg, P < 0.001) of HF”
Quote in the paperNot a substantial claim - Findingown data
These observations were extended by demonstrating favourable effects of tirzepatide relative to dulaglutide on the composite heart failure endpoint.
“These observations were extended by demonstrating favourable effects of tirzepatide relative to dulaglutide on the composite HF endpoint.”
Quote in the paperSubstantial claim - Findingown data
Patients treated with tirzepatide demonstrated greater reductions in HbA1c in the absence of heart failure (-1.68 vs -0.87%, P < 0.001).
“or absence (-1.68 vs. -0.87%,P < 0.001) of HF”
Quote in the paperNot a substantial claim - Findingown data
There was no evidence of statistical heterogeneity regarding the effects of tirzepatide and dulaglutide on composite heart failure endpoints on baseline subgroup analysis.
“There was no evidence of statistical heterogeneity regarding the effects of tirzepatide and dulaglutide on composite HF endpoints on baseline subgroup analysis”
Quote in the paperNot a substantial claim - Findingown data
Tirzepatide produced a smaller reduction in eGFR in the absence of heart failure (-7.2 vs -8.1 mL/min/1.73 m2).
“or absence (-7.2 vs. -8.1 mL/min/1.73 m 2 ) of HF”
Quote in the paperNot a substantial claim - Findingown data
The incidence of gastrointestinal adverse events was greater in the tirzepatide group compared with dulaglutide-treated patients in the presence and absence of a history of heart failure.
“The incidence of gastrointestinal adverse events was greater in the tirzepatide group compared with dulaglutide-treated patients in the presence and absence of a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, the composite of MACE-3 occurred in 10.9% of the tirzepatide group and 11.6% of the dulaglutide group (HR 0.93, 95% CI 0.83-1.04).
“and in 10.9% of the tirzepatide group and 11.6% of the dulaglutide group (HR 0.93, 95%CI 0.83-1.04) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In the overall cohort, the transformed APPADL score at baseline was lower in patients with a history of heart failure (54.0 vs 61.5 units).
“In the overall cohort, the transformed APPADL score (54.0 vs. 61.5 UNITS) and EQ-5D-5L visual analogue score (68.9 vs. 74.6UNITS) at baseline were lower in patients with a history of HF”
Quote in the paperNot a substantial claim - Findingown data
In patients with high or very-high risk chronic kidney disease at baseline and no history of heart failure, the change in eGFR from baseline to 36 months was -5.9 vs -9.0 mL/min/1.73 m2 with tirzepatide vs dulaglutide, respectively (between-group difference 3.1, 95% CI 1.9-4.3).
“and -5.9 vs. -9.0 mL/min/1.73 m 2 (between group difference 3.1, 95%CI 1.9-4.3) in patients without a history of HF”
Quote in the paperNot a substantial claim - Findingown data
At month 48, patients treated with tirzepatide demonstrated a greater EQ-5D-5L visual analogue score in patients without a history of heart failure (77.1 vs 75.2 units, P < 0.001).
“and without (77.1 vs. 75.2UNITS, P < 0.001) a history of HF”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, the composite of death due to any cause or hospitalization or urgent visits for heart failure occurred in 8.6% of the tirzepatide group and 9.7% of the dulaglutide group (HR 0.88, 95% CI 0.78-1.00).
“and in 8.6% of the tirzepatide group and 9.7% of the dulaglutide group (HR 0.88, 95%CI 0.78-1.00) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In the overall cohort, the EQ-5D-5L visual analogue score at baseline was lower in patients with a history of heart failure (68.9 vs 74.6 units).
“In the overall cohort, the transformed APPADL score (54.0 vs. 61.5 UNITS) and EQ-5D-5L visual analogue score (68.9 vs. 74.6UNITS) at baseline were lower in patients with a history of HF”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, all-cause death occurred in 7.4% of the tirzepatide group and 8.4% of the dulaglutide group (HR 0.86, 95% CI 0.75-0.99).
“and in 7.4% of the tirzepatide group and 8.4% of the dulaglutide group (HR 0.86, 95%CI 0.75-0.99) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, myocardial infarction occurred in 4.4% of the tirzepatide group and 5.3% of the dulaglutide group (HR 0.83, 95% CI 0.70-0.99).
“and in 4.4% of the tirzepatide group and 5.3% of the dulaglutide group (HR 0.83, 95%CI 0.70-0.99) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, the hazard ratio for MACE-4 was 0.91 (95% CI 0.83-1.00).
“and for MACE-4 0.81 (95%CI 0.69-0.95) and 0.91 (95%CI 0.83-1.00) in patients with and without HF, respectively.”
Quote in the paperNot a substantial claim - Findingnone given
The primary endpoint of SURPASS-CVOT demonstrated non-inferiority of tirzepatide compared with dulaglutide on the primary MACE endpoint.
“As the primary endpoint of SURPASS-CVOT demonstrated non-inferiority of tirzepatide compared with dulaglutide on the primary MACE endpoint, all subsequent analyses should be considered”
Quote in the paperSubstantial claim - Findingown data
The reduction in the composite heart failure endpoint was predominantly driven by a reduction in fatal events, compared with hospitalization or urgent visits for heart failure.
“It should be noted that this hypothesisgenerating finding was predominantly driven by a reduction in fatal events, compared with hospitalization or urgent visits for HF.”
Quote in the paperSubstantial claim - Findingown data
In patients with a history of heart failure, the composite of cardiovascular death or hospitalization or urgent visits for heart failure occurred in 14.4% of the tirzepatide group and 16.7% of the dulaglutide group (HR 0.85, 95% CI 0.70-1.03).
“The composite of CV death or hospitalization or urgent visits for HF occurred in 14.4% of the tirzepatide group and 16.7% of the dulaglutide group (HR 0.85, 95%CI 0.70-1.03) in patients with a history of HF”
Quote in the paperSubstantial claim - Findingown data
In patients without a history of heart failure, the hazard ratio for cardiovascular death or hospitalization or urgent visits for heart failure was 0.96 (95% CI 0.83-1.12).
“The HR for CV death or hospitalization or urgent visits for HF was 0.85 (95%CI 0.70-1.03)and 0.96 (95%CI 0.83-1.12),for MACE-3 0.90 (95%CI 0.76-1.08)and 0.93 (95%CI 0.83-1.04),and for MACE-4 0.81 (95%CI 0.69-0.95) and 0.91 (95%CI 0.83-1.00) in patients with and without HF, respectively.”
Quote in the paperNot a substantial claim - Findingown data
In patients with a history of heart failure, the hazard ratio for MACE-4 was 0.81 (95% CI 0.69-0.95).
“and for MACE-4 0.81 (95%CI 0.69-0.95) and 0.91 (95%CI 0.83-1.00) in patients with and without HF, respectively.”
Quote in the paperSubstantial claim - Findingown data
In patients with a history of heart failure, the hazard ratio for all-cause death or hospitalization or urgent visits for heart failure on tirzepatide vs dulaglutide was 0.83 (95% CI 0.70-0.99).
“The hazard ratio (HR) for all-cause death or hospitalization or urgent visits for HF on tirzepatide vs. dulaglutide was 0.83 [95% confidence interval (CI) 0.70-0.99] in patients with HF”
Quote in the paperSubstantial claim - Findingown data
In patients without a history of heart failure, the composite of MACE-4 occurred in 15.5% of the tirzepatide group and 16.9% of the dulaglutide group (HR 0.91, 95% CI 0.83-1.00).
“and in 15.5% of the tirzepatide group and 16.9% of the dulaglutide group (HR 0.91, 95%CI 0.83-1.00) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Findingown data
A greater proportion of patients treated with dulaglutide underwent initiation of treatment with an SGLT2 inhibitor after commencement of the trial in the group with a history of heart failure (26.9% vs 21.8%, P = 0.006).
“A greater proportion of patients trea- ted with dulaglutide underwent initiation of treatment with an SGLT2 inhibitor after commencement of the trial in the group with (26.9% vs. 21.8%, P = 0.006)”
Quote in the paperNot a substantial claim - Findingown data
In patients without a history of heart failure, stroke occurred in 3.3% of the tirzepatide group and 3.5% of the dulaglutide group (HR 0.92, 95% CI 0.75-1.14).
“and in 3.3% of the tirzepatide group and 3.5% of the dulaglutide group (HR 0.92, 95%CI 0.75-1.14) in patients without a history of HF.”
Quote in the paperNot a substantial claim - Interpretationown data
This prespecified, exploratory analysis extended these observations to reaffirm findings on conventional cardiovascular events with tirzepatide compared with dulaglutide in those with and without a history of heart failure.
“This prespecified, exploratory analysis extended these observations to reaffirm findings on conventional CV events with tirzepatide compared with dulaglutide in those with and without a history of HF.”
Quote in the paperSubstantial claim - Interpretationreasoning
Overall, the results suggest that tirzepatide may be a useful treatment for people with type 2 diabetes and heart or blood vessel disease, including those with heart failure who are at high risk of future heart problems.
“Overall, these results suggest that tirzepatide may be a useful treatment for people with type 2 diabetes and heart or blood vessel disease, including those with heart failure who are at high risk of future heart problems.”
Quote in the paperSubstantial claim - Interpretationcitation
The greater weight loss achieved with tirzepatide versus dulaglutide in this trial may be relevant to the quality-of-life findings, given that greater weight loss has been associated with greater KCCQ benefits in prior studies of incretins in patients with heart failure with preserved ejection fraction.
“The greater weight loss achieved with tirzepatide vs. dulaglutide in this trial may be relevant to these findings, given that greater weight loss has been associated with greater KCCQ benefits in prior studies of incretins in patients living with HFpEF.[13][14][15]”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [13] Packer, 2025, Tirzepatide for heart failure with preserved ejection fraction and obesity, N Engl J Med source
- cites [14] Packer, 2025, Influence of type 2 diabetes on the effects of tirzepatide in patients with heart failure and a preserved ejection fraction with obesity, J Am Coll Cardiol source
Checked before — its earlier verdict is held back until a new check runs.
- cites [15] Sattar, 2025, The association between tirzepatide versus insulin glargine and NT-proBNP levels in people with type 2 diabetes with or at elevated risk for cardiovascular disease: post hoc analyses of SURPASS 4, Circulation source
Checked before — its earlier verdict is held back until a new check runs.
- Interpretationreasoning
The finding does not point to a heart failure-specific benefit.
“While this endpoint is of interest to patients with HF and their treating clinicians, the finding does not point to an HF-specific benefit.”
Quote in the paperSubstantial claim - Premisecitation
These findings were present in patients with or without type 2 diabetes.
“These findings were present in patients with or without T2D.14,15”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [14] Packer, 2025, Influence of type 2 diabetes on the effects of tirzepatide in patients with heart failure and a preserved ejection fraction with obesity, J Am Coll Cardiol source
Checked before — its earlier verdict is held back until a new check runs.
- cites [15] Sattar, 2025, The association between tirzepatide versus insulin glargine and NT-proBNP levels in people with type 2 diabetes with or at elevated risk for cardiovascular disease: post hoc analyses of SURPASS 4, Circulation source
Checked before — its earlier verdict is held back until a new check runs.
- Interpretationreasoning
These findings further establish the potential benefits of the use of tirzepatide in people with type 2 diabetes at a high risk of experiencing cardiovascular events.
“These findings further establish the potential benefits of the use of tirzepatide in people with T2D at a high risk of experiencing CV events.”
Quote in the paperSubstantial claim - Interpretationreasoning
In patients with a prior history of heart failure, the higher rate of MACE means the potential impact of tirzepatide on absolute event rates is likely greater.
“Given the higher rate of MACE in those with a prior history of HF, the potential impact of tirzepatide on absolute event rates is therefore likely to be greater, which may have implications for clinical decision-making.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
The analysis cannot infer which heart failure phenotype might be driving the observed clinical effects.
“Accordingly, the analysis is not able to make an inference about which HF phenotype might be driving the observed clinical effects.”
Quote in the paperSubstantial claim - Interpretationown data
The benefits of tirzepatide on risk factors and clinical outcomes extend to functional measures that are important for people living with type 2 diabetes and atherosclerotic cardiovascular disease.
“This extends the benefits of tirzepatide on risk factors and clinical outcomes to functional measures that are important for people living with T2D and ASCVD.”
Quote in the paperSubstantial claim
- Probably not a substantial claim. 24
- It may state two separate claims as one. 25
- The quote only partly states this claim. 1
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationPrevious studies in people with obesity-associated heart failure with preserved ejection fraction showed greater improvements in 6-minute walk distance and quality of life measures and preliminary evidence of a reduction in cardiovascular events, though these studies were small and relatively short in duration.
“This has been evidenced by demonstrating greater improvements in 6-minute walk distance and quality of life measures and preliminary evidence of a reduction in CV events in these studies, which were small and relatively short in duration.”
Quote in the paperNot a substantial claim3 of 4 sources checked- cites [6] Kosiborod, 2023, Semaglutide in patients with heart failure with preserved ejection fraction and obesity, N Engl J Med source
- cites [13] Packer, 2025, Tirzepatide for heart failure with preserved ejection fraction and obesity, N Engl J Med source
- cites [14] Packer, 2025, Influence of type 2 diabetes on the effects of tirzepatide in patients with heart failure and a preserved ejection fraction with obesity, J Am Coll Cardiol source
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured - cites [15] Sattar, 2025, The association between tirzepatide versus insulin glargine and NT-proBNP levels in people with type 2 diabetes with or at elevated risk for cardiovascular disease: post hoc analyses of SURPASS 4, Circulation source
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationPrevious studies have demonstrated favourable effects of semaglutide and tirzepatide in people with obesity-associated heart failure with preserved ejection fraction.
“Previous studies have demonstrated favourable effects of both the GLP-1 receptor agonist, semaglutide, and the GIP/GLP-1 receptor agonist, tirzepatide, in people with obesity associated HFpEF.6,[13][14][15]”
Quote in the paperNot a substantial claim3 of 4 sources checked- cites [6] Kosiborod, 2023, Semaglutide in patients with heart failure with preserved ejection fraction and obesity, N Engl J Med source
- cites [13] Packer, 2025, Tirzepatide for heart failure with preserved ejection fraction and obesity, N Engl J Med source
- cites [14] Packer, 2025, Influence of type 2 diabetes on the effects of tirzepatide in patients with heart failure and a preserved ejection fraction with obesity, J Am Coll Cardiol source
- cites [15] Sattar, 2025, The association between tirzepatide versus insulin glargine and NT-proBNP levels in people with type 2 diabetes with or at elevated risk for cardiovascular disease: post hoc analyses of SURPASS 4, Circulation source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
InterpretationcitationGLP-1 receptor agonists and tirzepatide improve multiple cardiometabolic pathways, including glycaemic control, blood pressure, inflammation, endothelial function, insulin sensitivity, and renal physiology, suggesting that both weight-loss-dependent and weight-loss-independent mechanisms likely contribute to their cardiovascular effects.
“In addition, GLP-1 receptor agonists and tirzepatide improve multiple cardiometabolic pathways, including glycaemic control, blood pressure, inflammation, endothelial function, insulin sensitivity, and renal physiology, suggesting that both weight-loss-dependent and weight-loss-independent mechanisms likely contribute to their CV effects.[16][17][18]”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [16] Ussher, 2023, Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action, Nat Rev Cardiol source
- cites [17] Mullur, 2024, GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms, J Endocrinol source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites [18] Moiz, 2026, GLP-1 Receptor agonists and blood pressure: a state-of-the-art review of mechanisms, evidence, and clinical implications, Am J Hypertens source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
It may state two separate claims as one.
PremisecitationClinical benefits of GLP-1 receptor agonists have been extended to heart failure, with improvements in 6-minute walk distance and quality of life, and a lower rate of hospitalization for heart failure in patients with obesity-associated heart failure with preserved ejection fraction.
“These clinical benefits have been extended to the setting of heart failure (HF), with improvements in 6-minute walk distance and quality of life, and a lower rate of hospitalization for HF in patients with obesity-associated HF with preserved ejection fraction (HFpEF).[6][7][8]”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [6] Kosiborod, 2023, Semaglutide in patients with heart failure with preserved ejection fraction and obesity, N Engl J Med source
The Discussion reports improved KCCQ scores and 6-minute walk distance with semaglutide in patients with obesity and HFpEF. The Supportive Secondary and Exploratory End Points section reports fewer *hospitalizations for heart failure or urgent visits* (1 versus 12), but does not establish a lower hospitalization rate separately; that part of the claim is more specific than the reported outcome. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [7] Davies, 2025, Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial, Lancet Diabetes Endocrinol source
The Results report benefits for 6-minute walk distance and KCCQ quality-of-life scores, and the Discussion describes improved exercise function in participants with obesity-related HFpEF and type 2 diabetes (page numbers unavailable). The paper does not establish a lower rate of heart-failure hospitalization; its Discussion says the trial collected few hospitalizations and urgent visits. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [8] Kosiborod, 2024, Semaglutide in patients with obesity-related heart failure and type 2 diabetes, N Engl J Med source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataPatients with a history of heart failure had greater body weight at baseline (96.3 vs 91.6 kg, P < 0.001).
“Patients with a history of HF had greater body weight (96.3 vs. 91.6 kg, P < 0.001)”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataA history of heart failure was associated with a greater rate of use of beta-blockers (78.3% vs 61.9%).
“A history of HF was associated with a greater rate of use of beta-blockers (78.3% vs. 61.9%)”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataCompared with dulaglutide, tirzepatide improved blood sugar, weight, blood pressure, and blood fats more.
“Compared with dulaglutide, tirzepatide improved blood sugar, weight, blood pressure, and blood fats more.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataAt month 48, patients treated with tirzepatide demonstrated a greater transformed APPADL score in patients with a history of heart failure (55.3 vs 51.4 units, P < 0.001).
“At month 48, patients treated with tirzepatide demonstrated a greater transformed APPADL score in patients with (55.3 vs. 51.4UNITS, P < 0.001)”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataA history of heart failure was associated with a greater rate of use of mineralocorticoid receptor agonists (24.3% vs 5.7%).
“mineralocorticoid receptor agonists (24.3% vs. 5.7%)”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataParticipants taking tirzepatide had fewer deaths, similar or fewer heart events and reported better quality of life, regardless of their history of heart failure.
“Participants taking tirzepatide had fewer deaths, similar or fewer heart events and reported better quality of life, regardless of their history of heart failure.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataPatients with a history of heart failure were more likely to have hypertension (95.6% vs 88.8%).
“and hypertension (95.6% vs. 88.8%).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataThe rate of discontinuation of study drug or loss to follow up did not differ between treatment groups or between those with or without a history of heart failure.
“The rate of discontinuation of study drug or loss to follow up did not differ between treatment groups or between those with or without a history of HF”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataIn the current exploratory analysis of SURPASS-CVOT, tirzepatide compared with dulaglutide was associated with a reduction in the composite of all-cause mortality and hospitalization or urgent visits for heart failure by 17% in those with a history of heart failure and by 12% in those without, both nominal differences.
“The current, exploratory analysis of SURPASS-CVOT demonstrated that treatment with tirzepatide, compared with dulaglutide, was associated with a reduction in the composite of all-cause mortality and hospitalization or urgent visits for HF by 17% in those with a history of HF and by 12% in those without HF, both nominal differences.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataTirzepatide compared with dulaglutide produced greater reductions in HbA1c, body weight, blood pressure, and atherogenic lipids, and slowed the reduction in eGFR, in both patients with and without a history of heart failure.
“The benefits of tirzepatide compared with dulaglutide, producing greater reductions in HbA1c, body weight, blood pressure, and atherogenic lipids, in addition to slowing the reduction in eGFR, were observed in both groups.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataA reduction in the incidence of MACE-3 was observed in both treatment groups, in patients with and without heart failure.
“A reduction of the incidence of MACE-3 was observed in both treatment groups, in patients with and without HF.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataA history of heart failure was associated with a greater rate of use of angiotensin-converting enzyme inhibitors (43.6% vs 38.9%).
“angiotensin-converting enzyme inhibitors (43.6% vs. 38.9%)”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataThe patient-reported outcomes of APPADL and EQ-5D-5L visual analogue scores improved and were higher on tirzepatide in both heart failure groups.
“The patient-reported outcomes of APPADL and EQ-5D-5L visual analogue scores improved and were higher on tirzepatide in both groups.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataAn extended post hoc analysis demonstrated that tirzepatide was associated with a reduced rate of the composite of all-cause mortality or hospitalization or urgent visits for heart failure and improved patient-reported outcomes compared with dulaglutide in patients with and without a history of heart failure.
“Furthermore, an extended post hoc analysis demonstrated that tirzepatide was associated with a reduced rate of the composite of all-cause mortality or hospitalization or urgent visits for HF and improved patient-reported outcomes compared with dulaglutide in patients with and without a history of HF.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataPatients with a history of heart failure were more likely to identify as White race (88.1% vs 79.7% of patients without a history of heart failure).
“Patients with a history of HF were more likely to identify as White race (88.1% vs. 79.7% of patients without a history of HF)”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataPatients with a history of heart failure were more likely to have a prior history of myocardial infarction (57.8% vs 44.5%).
“and have a prior history of myocardial infarction (57.8% vs. 44.5%)”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataMore than one in five patients commenced treatment with an SGLT2 inhibitor during the trial.
“We observed that more than one in five patients commenced treatment with an SGLT2 inhibitor during the trial.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataA history of heart failure was associated with a greater rate of use of loop diuretics (43.3% vs 16.4%).
“and loop diuretics (43.3% vs. 16.4%).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataPeople with a history of heart failure reported worse quality of life measures at baseline and greater deterioration over time.
“These assessments revealed that people with a history of HF reported worse quality of life measures at baseline and greater deterioration over time.”
Quote in the paperSubstantial claimProbably not a substantial claim. It may state two separate claims as one.
Study design and conductreasoningSURPASS-CVOT was conducted in people with type 2 diabetes and atherosclerotic cardiovascular disease and was not a specific heart failure study, so the patient-reported outcome assessments employed were more generalized in scope.
“Given that SURPASS-CVOT was conducted in people with T2D and ASCVD and was not a specific HF study, the patient-reported outcome assessments employed were more generalized in their scope.”
Quote in the paperSubstantial claimProbably not a substantial claim.
Study design and conductnone givenClinical events were adjudicated by an independent committee that was blinded to treatment status.
“Clinical events were adjudicated by an independent committee that was blinded to treatment status.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Study design and conductnone givenSURPASS-CVOT was not specifically designed for people with heart failure, and heart failure groups were identified by self-reported clinical history.
“SURPASS-CVOT was not a study specifically designed for people with HF, and groups were identified by self-reported clinical history.”
Quote in the paperSubstantial claim- Rests on an assumption: Self-reported clinical history accurately identifies patients with heart failure.
Probably not a substantial claim. It may state two separate claims as one.
Study design and conductreasoningThe current analysis employed both all-cause and cardiovascular death, whereas the primary analysis of SURPASS-CVOT integrated the heart failure composite outcome including cardiovascular death.
“While the primary analysis of SURPASS-CVOT integrated the HF composite outcome, including CV death, the current analysis employed both all-cause and CV death, given their relevance in the settings of both T2D and HF.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
Study design and conductnone givenThe profile of sex, race, and geographical representation of people in the trial may limit generalizability of the findings.
“The profile of sex, race, and geographical representation of people in the trial may limit generalizability of the findings.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationAdministration of tirzepatide in patients with obesity and HFpEF was reported to produce favourable effects on 6-minute walk distance, quality of life and the composite of cardiovascular death or heart failure events in a modest-sized trial with small event numbers.
“Administration of tirzepatide in patients with obesity and HFpEF was reported to produce favourable effects on 6-minute walk distance, quality of life and the composite of CV death or HF events in a modest-sized trial with small event numbers.13”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Packer, 2025, Tirzepatide for heart failure with preserved ejection fraction and obesity, N Engl J Med source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductnone givenSURPASS-CVOT was an active comparator trial and did not involve a direct comparison with placebo.
“SURPASS-CVOT was an active comparator trial and did not involve a direct comparison with placebo.”
Quote in the paperNot a substantial claimProbably not a substantial claim. It may state two separate claims as one.
Study design and conductreasoningThe heart failure finding is from an exploratory analysis and should be considered hypothesis-generating.
“This is an exploratory analysis and the findings should be considered hypothesis-generating.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Study design and conductreasoningBecause patients with class IV heart failure or recent hospitalization were excluded, the findings do not apply to them.
“Similarly, as patients with class IV HF or recent hospitalization were excluded, the findings do not apply to them.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Study design and conductown dataSURPASS-CVOT was a Phase 3, event-driven, multicentre, international, randomized, double-blind, active comparator study comparing tirzepatide up to 15 mg and dulaglutide 1.5 mg administered once weekly when added to standard of care in patients with type 2 diabetes with established cardiovascular disease.
“SURPASS-CVOT (ClinicalTrials.govID NCT04255433) was a Phase 3, event-driven, multicentre, international, randomized, doubleblind, active comparator study comparing tirzepatide up to 15 mg and dulaglutide 1.5 mg administered once weekly when added to the standard of care in patients with T2D with established CV disease.”
Quote in the paperSubstantial claimProbably not a substantial claim. It may state two separate claims as one.
Study design and conductnone givenThe present manuscript analyses were not subjected to family-wise type 1 error rate control, and all findings should thus be considered exploratory.
“The present manuscript analyses were not subjected to family-wise type 1 error rate control, and all findings should thus be considered exploratory.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationIn the REWIND cardiovascular outcome study, compared with placebo, dulaglutide reduced the rate of MACE-3, and a modest reduction in the composite heart failure endpoint of cardiovascular death and urgent heart failure visits was also observed.
“In the REWIND CV outcome study (CVOT), when compared with placebo, dulaglutide reduced the rate of MACE-3, and a modest reduction in the composite HF endpoint of CV death and urgent HF visits was also observed.23”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Branch, 2022, Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post-hoc analysis from the REWIND randomized trial, Eur J Heart Fail source
It may state two separate claims as one.
Study design and conductown dataA total of 13,299 patients were randomized at 640 sites across 30 countries globally, in a 1:1 ratio to tirzepatide or dulaglutide, stratified according to country of enrolment and sodium-glucose cotransporter-2 inhibitor use.
“A total of 13 299 patients were randomized at 640 sites across 30 countries globally, in a 1:1 ratio to tirzepatide or dulaglutide, stratified according to country of enrolment and sodium-glucose cotransporter-2 inhibitor (SGLT-2i) use.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Interpretationnone givenThe post hoc inclusion of all-cause death reflects the increased mortality rate, due to both cardiovascular and non-cardiovascular causes, in patients with type 2 diabetes, atherosclerotic cardiovascular disease, and heart failure.
“The post hoc inclusion of all-cause death reflects the increased mortality rate, due to both CV and non-CV causes, in patients with T2D, ASCVD, and HF.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenAnalyses were not adjusted for multiplicity of statistical testing.
“Analyses were not adjusted for multiplicity of statistical testing.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationThe findings of these studies have been integrated into clinical guidelines recommending increasing use of GLP-1 receptor agonists for many high-risk patients.
“The findings of these studies have been integrated into clinical guidelines recommending their increasing use for many high-risk patients.9”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] Diabetes* ADAPPCf, 2026, 9. pharmacologic approaches to glycemic treatment: standards of care in diabetes—2026, Diabetes Care source
Checked before — its earlier verdict is held back until a new check runs.
It may state two separate claims as one.
PremisecitationTirzepatide is a dual agonist at the GLP-1 and glucose-dependent insulinotropic polypeptide receptors and has been demonstrated to produce incremental benefits on glycaemic control, weight loss and associated metabolic risk factors in patients with type 2 diabetes compared with selective GLP-1 receptor agonists.
“Tirzepatide is a dual agonist at the GLP-1 and glucosedependent insulinotropic polypeptide (GIP) receptors and has been demonstrated to produce incremental benefits on glycaemic control, weight loss and associated metabolic risk factors in patients with T2D in comparison with selective GLP-1 receptor agonists.[10][11][12]”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [10] Del Prato, 2021, Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial, Lancet source
- cites [11] Frías Juan, 2021, Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes, N Engl J Med source
- cites [12] Nicholls, 2024, Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS clinical trial program, Cardiovasc Diabetol source
Checked before — its earlier verdict is held back until a new check runs.
It may state two separate claims as one.
Premiseown dataThe SURPASS-CVOT study established the cardiovascular efficacy of tirzepatide by demonstrating that its effects on MACE-3 were non-inferior to dulaglutide, an agent that had previously been found to reduce cardiovascular risk in patients with type 2 diabetes and atherosclerotic cardiovascular disease.
“The SURPASS-CVOT study established the CV efficacy of tirzepatide, by demonstrating that its effects on MACE-3 were noninferior to dulaglutide, an agent that had previously been found to reduce CV risk in patients with T2D and ASCVD.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductnone givenAll statistical analyses involved the prespecified hierarchical approach and subgroup analysis included interaction testing; the latter should be considered nominal.
“All statistical analyses involved the prespecified hierarchical approach and subgroup analysis included interaction testing; the latter should be considered nominal.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The impact of tirzepatide on key outcomes of interest, including heart failure events and cardiovascular death as well as quality of life measures, in this population with heart failure and diabetes has not been well elucidated.
“The impact of tirzepatide on key outcomes of interest-including HF events and CV death as well as quality of life measures-in this population with HF and diabetes has not been well elucidated.”
The paper relies on this without support.
The MACE-3 reduction demonstrated by dulaglutide versus placebo in prior trials is applicable to the SURPASS-CVOT population and can be used to impute placebo effects for tirzepatide.
“Based on the original study design, establishing non-inferiority to an agent which had previously demonstrated a reduction in MACE-3 risk compared with placebo, confirms the CV benefits of tirzepatide compared with an imputed placebo.19”
The paper relies on this without support.
Self-reported clinical history accurately identifies patients with heart failure.
“SURPASS-CVOT was not a study specifically designed for people with HF, and groups were identified by self-reported clinical history.”
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.
Clinical benefits were not restricted to fatal outcomes
MinorThe paper says the observed clinical benefits were restricted to fatal outcomes, but Table 3 reports fewer coronary revascularizations with tirzepatide in both heart-failure subgroups, with confidence intervals excluding 1. Coronary revascularization is a nonfatal outcome.
“The clinical benefits observed in this analysis were restricted to fatal outcomes.”
“Coronary revascularization 103 (7.9) 138 (10.1) 0.76 (0.59-0.98) 424 (8.0) 479 (9.2) 0.87 (0.76-0.99)”
Citations
Cites
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2307563 · Cited by 3,236
Self-citationGerstein, H. C., Colhoun, H. M., Dagenais, G. R., Diaz, R., Lakshmanan, M., Pais, P., Probstfield, J., Riesmeyer, J. S., Riddle, M. C., Rydén, L., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31149-3 · Cited by 3,163
Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.
Perkovic, V., Tuttle, K. R., Rossing, P., Mahaffey, K. W., Mann, J. F. E., Bakris, G., Baeres, F. M. M., Idorn, T., Bosch-Traberg, H., Lausvig, N. L., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403347 · Cited by 2,099
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
Frías, J. P., Davies, M. J., Rosenstock, J., Pérez Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., Cui, X., & Brown, K. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107519 · Cited by 2,096
Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
Kosiborod, M. N., Abildstrøm, S. Z., Borlaug, B. A., Butler, J., Rasmussen, S., Davies, M., Hovingh, G. K., Kitzman, D. W., Lindegaard, M. L., Møller, D. V., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2306963 · Cited by 1,669
Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity
Packer, M., Zile, M. R., Kramer, C. M., Baum, S. J., Litwin, S. E., Menon, V., Ge, J., Weerakkody, G. J., Ou, Y., Bunck, M. C., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2410027 · Cited by 1,009
Self-citationSemaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes
Kosiborod, M. N., Petrie, M. C., Borlaug, B. A., Butler, J., Davies, M. J., Hovingh, G. K., Kitzman, D. W., Møller, D. V., Treppendahl, M. B., Verma, S., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2313917 · Cited by 758
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Self-citationGlucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action
Ussher, J. R., & Drucker, D. J. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00849-3 · Cited by 577
Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes
McGuire, D. K., Marx, N., Mulvagh, S. L., Deanfield, J. E., Inzucchi, S. E., Pop-Busui, R., Mann, J. F. E., Emerson, S. S., Poulter, N. R., Engelmann, M. D. M., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2501006 · Cited by 416
Self-citation9. pharmacologic approaches to glycemic treatment: standards of care in diabetes—2026
American Diabetes Association Professional Practice Committee for Diabetes*, Bajaj, M., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Briggs Early, K., ChallaSivaKanaka, S., et al. (2026) · Diabetes Care · doi:10.2337/dc26-s009 · Cited by 263
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Self-citationCardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes
Nicholls, S. J., Pavo, I., Bhatt, D. L., Buse, J. B., Del Prato, S., Kahn, S. E., Lincoff, A. M., McGuire, D. K., Miller, D., Nauck, M. A., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2505928 · Cited by 223
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Self-citationGLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms
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Metadata
- Authors
- Nicholls, S. J., Pavo, I., Bhatt, D. L., Buse, J. B., Del Prato, S., Franco, D. R., Kahn, S. E., Lincoff, A. M., Martins, R. F., McGuire, D. K., Mehta, V., Miller, D., Nauck, M. A., Nishiyama, H., Nissen, S. E., Nyolczas, N., Sattar, N., Weerakkody, G., Wiese, R. J., Zinman, B., Zoungas, S., & D’Alessio, D.
- Affiliations
- Monash University (AU)
- Eli Lilly (United States) (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of North Carolina at Chapel Hill (US)
- Interdisciplinary Research Center ‘Health Science’, Sant’Anna School of Advanced Studies , Pisa ,
- CPCLIN/DASA Clinical Research Center , Sao Paulo ,
- University of Washington (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Parkland Health & Hospital System (US)
- Govind Ballabh Pant Hospital (IN)
- Universitätsmedizin Greifswald (DE)
- Cleveland Clinic (US)
- Central Hospital of Northern Pest - Military Hospital , Budapest ,
- University of Glasgow (GB)
- Mount Sinai Hospital (CA)
- The George Institute for Global Health (AU)
- Duke Medical Center (US)
- ORCID
- Nicholls, Stephen J
- Pavo, Imre
- Bhatt, Deepak L
- Buse, John B
- Del Prato, Stefano
- Franco, Denise R
- Kahn, Steven E
- Lincoff, A Michael
- McGuire, Darren K
- Mehta, Vimal
- Miller, Debra
- Nauck, Michael A
- Nishiyama, Hiroshi
- Nissen, Steven E
- Nyolczas, Noémi
- Sattar, Naveed
- Weerakkody, Govinda
- Wiese, Russell J
- Zinman, Bernard
- Zoungas, Sophia
- D’Alessio, David
- Venue
- European Journal of Preventive Cardiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2026-10-15
- ISSN
- 2047-4873 (ISSN-L)
- 2047-4881
- OpenAlex
- W7221920289
- Cited by
- 0
- References
- 23
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Preventive Cardiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- tirzepatide, dulaglutide, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, major adverse cardiovascular events, cardiovascular mortality, myocardial infarction, stroke, all-cause mortality, heart failure hospitalization, GLP-1 receptor agonists, SGLT2 inhibitors, patient-reported outcomes, non-inferiority
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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.
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