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Cited by 465Diabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and Research

10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023

Open access
ElSayed, Nuha A., Aleppo, Grazia, Aroda, Vanita R., Bannuru, Raveendhara R., Brown, Florence M., Bruemmer, Dennis, Collins, Billy S., Das, Sandeep R. +14 more·2023·Diabetes Care
DOI 10.2337/dc23-s010PMC PMC9810475
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Abstract

The American Diabetes Association (ADA) “Standards of Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

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  • Premisecitation
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 1

    Rates of heart failure hospitalization have been improved in recent trials of people with type 2 diabetes, most of whom also had ASCVD, using SGLT2 inhibitors.

    “Rates of heart failure hospitalization have been improved in recent trials including people with type 2 diabetes, most of whom also had ASCVD, with sodium -glucose cotransporter 2 (SGLT2) inhibitors (8 -11).”
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    • cites [8] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source

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    • cites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

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    • cites [10] Fitchett, 2018, Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME trial, Eur Heart J source

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    • cites [11] McMurray, 2019, Dapagliflozin in patients with heart failure and reduced ejection fraction, N Engl J Med source

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  • Premisereasoning
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 1

    Addressing multiple cardiovascular risk factors at the same time produces large benefits.

    “Furthermore, large bene fi ts are seen when multiple cardiovascular risk factors are addressed simultaneously.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Common conditions coexisting with type 2 diabetes, such as hypertension and dyslipidemia, are risk factors for ASCVD, and diabetes itself confers independent risk.
  • Premisecitation
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 1

    Controlling individual cardiovascular risk factors prevents or slows atherosclerotic cardiovascular disease in people with diabetes, according to numerous studies.

    “Numerous studies have shown the ef fi cacy of controlling individual cardiovascular risk factors in preventing or slowing ASCVD in people with diabetes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Common conditions coexisting with type 2 diabetes, such as hypertension and dyslipidemia, are risk factors for ASCVD, and diabetes itself confers independent risk.
  • Premisecitation
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 1

    ASCVD morbidity and mortality have decreased.

    “ASCVD morbidity and mortality have decreased (3,4).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Buse, 2007, Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association, Diabetes Care source

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    • cites [4] Gaede, 2008, Effect of a multifactorial intervention on mortality in type 2 diabetes, N Engl J Med source

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  • Premisecitation
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 1

    Measures of 10-year coronary heart disease risk among U.S. adults with diabetes have improved significantly over the past decade.

    “there is evidence that measures of 10-year CHD risk among U.S. adults with diabetes have improved signi fi cantly over the past decade (2)”
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    • cites [2] Ali, 2013, Achievement of goals in U.S. diabetes care, 1999-2010, N Engl J Med source

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    Premisecitation
    § THE RISK CALCULATOR · p. 2

    Overall risk prediction of the ACC/AHA ASCVD risk calculator does not differ between people with and without diabetes, despite calibration variability in some subgroups.

    “Although some variability in calibration exists in various subgroups, including by sex, race, and diabetes, the overall risk prediction does not differ in those with or without diabetes (13 -16), validating the use of risk calculators in people with diabetes.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [13] Blood Pressure Lowering Treatment Trialists’ Collaboration, 2014, Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data, Lancet source

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    • cites [14] Grundy, 2019, 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, J Am Coll Cardiol source

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    • cites [15] Muntner, 2014, Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations, JAMA source

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    • cites [16] DeFilippis, 2017, Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American Heart Association-American College of Cardiology-Atherosclerotic Cardiovascular Disease risk score in a modern multi-ethnic cohort, Eur Heart J

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    Premisecitation
    § HYPERTENSION/BLOOD PRESSURE CONTROL · p. 2

    Antihypertensive therapy reduces ASCVD events, heart failure, and microvascular complications, according to numerous studies.

    “Moreover, numerous studies have shown that antihypertensive therapy reduces ASCVD events, heart failure, and microvascular complications.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Hypertension is a major risk factor for both ASCVD and microvascular complications.

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    Premisecitation
    § THE RISK CALCULATOR · p. 2

    Risk scores and other cardiovascular biomarkers have been developed for risk stratification of secondary prevention patients but are not yet in widespread use.

    “Recently, risk scores and other cardiovascular biomarkers have been developed for risk strati fi cation of secondary prevention patients (i.e., those who are already high risk because they have ASCVD) but are not yet in widespread use (17,18).”
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    • cites [17] Bohula, 2017, Atherothrombotic risk stratification and ezetimibe for secondary prevention, J Am Coll Cardiol source

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    • cites [18] Bohula, 2016, Atherothrombotic risk stratification and the efficacy and safety of vorapaxar in patients with stable ischemic heart disease and previous myocardial infarction, Circulation source

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    Premisecitation
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 2

    SGLT2 inhibitors reduce the risk of heart failure hospitalization, cardiovascular mortality, and all-cause mortality in people with and without cardiovascular disease.

    “A recent meta-analysis indicated that SGLT2 inhibitors reduce the risk of heart failure hospitalization, cardiovascular mortality, and all-cause mortality in people with (secondary prevention) and without (primary prevention) cardiovascular disease (12).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Arnott, 2020, Sodium-glucose cotransporter 2 inhibition for the prevention of cardiovascular events in patients with type 2 diabetes mellitus: a systematic review and meta-analysis, J Am Heart Assoc source

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    Premisecitation
    § 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes -2023 · p. 1

    Hypertension is often a precursor of heart failure of either type, ASCVD can coexist with either type, and prior myocardial infarction is often a major factor in heart failure with reduced ejection fraction.

    “Hypertension is often a precursor of heart failure of either type, and ASCVD can coexist with either type (7), whereas prior myocardial infarction (MI) is often a major factor in HFrEF.”
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    • cites [7] Lam, 2018, Heart failure with preserved ejection fraction: from mechanisms to therapies, Eur Heart J source

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    § THE RISK CALCULATOR · p. 2

    The ACC/AHA ASCVD risk calculators do not account for duration of diabetes or presence of diabetes complications such as albuminuria.

    “these risk calculators do not account for the duration of diabetes or the presence of diabetes complications, such as albuminuria.”
    Quote in the paperNot a substantial claim

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    Premisecitation
    § Meta-analyses of Trials · p. 4

    An analysis of trials including people with type 2 diabetes and impaired glucose tolerance with achieved systolic blood pressures below 135 mmHg in the intensive group and below 140 mmHg in the standard group revealed a 10% reduction in all-cause mortality and a 17% reduction in stroke.

    “An analysis of trials including people with type 2 diabetes and impaired glucose tolerance with achieved systolic blood pressures of < 135 mmHg in the intensive blood pressure treatment group and < 140 mmHg in the standard treatment group revealed a 10% reduction in all-cause mortality and a 17% reduction in stroke (30).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Bangalore, 2011, Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials, Circulation source

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    Premisecitation
    § Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control · p. 4

    In the HOT trial, cardiovascular event rates were not significantly different between diastolic blood pressure targets, although the lowest incidence of cardiovascular events occurred with an achieved diastolic blood pressure of 82 mmHg.

    “The cardiovascular event rates, de fi ned as fatal or nonfatal MI, fatal and nonfatal strokes, and all other cardiovascular events, were not signi fi cantly different between diastolic blood pressure targets ( # 90 mmHg, # 85 mmHg, and # 80 mmHg), although the lowest incidence of cardiovascular events occurred with an achieved diastolic blood pressure of 82 mmHg.”
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    • cites [37] Hansson, 1998, Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial, Lancet source

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    Premisecitation
    § Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control · p. 4

    The results of ACCORD BP and SPRINT have been interpreted as generally consistent, but ACCORD BP was viewed as underpowered because the composite primary end point was less sensitive to blood pressure regulation.

    “The results have been interpreted to be generally consistent between both trials, but ACCORD BP was viewed as underpowered due to the composite primary end point being less sensitive to blood pressure regulation (33).”
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    • cites [33] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med source

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    Premisecitation
    § Meta-analyses of Trials · p. 4

    More intensive reduction to below 130 mmHg was associated with a further reduction in stroke but not other cardiovascular events.

    “More intensive reduction to < 130 mmHg was associated with a further reduction in stroke but not other cardiovascular events.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Bangalore, 2011, Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials, Circulation source

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    Premisecitation
    § Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control · p. 4

    In the STEP trial, hypotension occurred more frequently in the intensive treatment group (3.4%) than in the standard treatment group (2.6%), without significant differences in other adverse events including dizziness, syncope, or fractures.

    “Hypotension occurred more frequently in the intensive treatment group (3.4%) compared with the standard treatment group (2.6%), without signi fi cant differences in other adverse events, including dizziness, syncope, or fractures.”
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    • cites [34] Zhang, 2021, Trial of intensive blood-pressure control in older patients with hypertension, N Engl J Med source

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    Premisecitation
    § Recommendations · p. 3

    Home blood pressure monitoring may improve patient medication taking and thus help reduce cardiovascular risk.

    “Moreover, home blood pressure monitoring may improve patient medication taking and thus help reduce cardiovascular risk (25).”
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    • cites [25] Omboni, 2013, Clinical usefulness and cost effectiveness of home blood pressure telemonitoring: meta-analysis of randomized controlled studies, J Hypertens source

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    Premisecitation
    § Meta-analyses of Trials · p. 4

    Among trials with lower baseline or attained blood pressure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albuminuria, but effects on other ASCVD outcomes and heart failure were not evident.

    “Among trials with lower baseline or attained blood pressure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albuminuria, but effects on other ASCVD outcomes and heart failure were not evident.”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [19] Whelton, 2018, 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, J Am Coll Cardiol source

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    • cites [26] Emdin, 2015, Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis, JAMA source

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    • cites [27] Arguedas, 2013, Blood pressure targets for hypertension in people with diabetes mellitus, Cochrane Database Syst Rev

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    • cites [29] Brunström, 2016, Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses, BMJ source

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    • cites [30] Bangalore, 2011, Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials, Circulation source

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    • cites [31] Thomopoulos, 2017, Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: 10 - Should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials, J Hypertens source

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    Premisecitation
    § Recommendations · p. 3

    Randomized clinical trials have demonstrated unequivocally that treatment of hypertension reduces cardiovascular events as well as microvascular complications.

    “Randomized clinical trials have demonstrated unequivocally that treatment of hypertension reduces cardiovascular events as well as microvascular complications (26 -32).”
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    • cites [26] Emdin, 2015, Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis, JAMA source

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    • cites [27] Arguedas, 2013, Blood pressure targets for hypertension in people with diabetes mellitus, Cochrane Database Syst Rev

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    • cites [28] Ettehad, 2016, Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis, Lancet source

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    • cites [29] Brunström, 2016, Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses, BMJ source

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    • cites [30] Bangalore, 2011, Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials, Circulation source

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    • cites [31] Thomopoulos, 2017, Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: 10 - Should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials, J Hypertens source

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    • cites [32] Xie, 2016, Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis, Lancet source

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    • Rests on an assumption: Hypertension is a major risk factor for both ASCVD and microvascular complications.

  • May combine two claims.

    Premisecitation
    § Recommendations · p. 3

    ACCORD BP did not confirm that targeting systolic blood pressure below 120 mmHg in people with diabetes results in decreased cardiovascular event rates, but the prespecified secondary outcome of stroke was reduced by 41% with intensive treatment.

    “While the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial (ACCORD BP) did not con fi rm that targeting a systolic blood pressure of < 120 mmHg in people with diabetes results in decreased cardiovascular event rates, the prespecifi ed secondary outcome of stroke was reduced by 41% with intensive treatment (35).”
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    • cites [35] Cushman, 2010, Effects of intensive blood-pressure control in type 2 diabetes mellitus, N Engl J Med source

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    Premisecitation
    § Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control · p. 4

    ACCORD BP and SPRINT targeted a similar systolic blood pressure below 120 mmHg, but the primary composite cardiovascular end point was nonsignificantly reduced in ACCORD BP.

    “Of note, the ACCORD BP and SPRINT trials targeted a similar systolic blood pressure < 120 mmHg, but in contrast to SPRINT, the primary composite cardiovascular end point was nonsigni fi cantly reduced in ACCORD BP.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med source

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    • cites [35] Cushman, 2010, Effects of intensive blood-pressure control in type 2 diabetes mellitus, N Engl J Med source

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    Interpretationcitation
    § Individualization of Treatment Targets · p. 4

    The benefits and risks of intensive blood pressure targets are uncertain and may vary across patients.

    “This approach acknowledges that the bene fi ts and risks of intensive blood pressure targets are uncertain and may vary across patients and is consistent with a patient-focused approach to care that values patient priorities and health care professional judgment (39).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] de Boer, 2018, Individualizing blood pressure targets for people with diabetes and hypertension: comparing the ADA and the ACC/AHA recommendations, JAMA source

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    Premisecitation
    § Recommendations · p. 3

    SPRINT demonstrated that treatment to a target systolic blood pressure below 120 mmHg decreases cardiovascular event rates by 25% in high-risk patients, although people with diabetes were excluded.

    “The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that treatment to a target systolic blood pressure of < 120 mmHg decreases cardiovascular event rates by 25% in high-risk patients, although people with diabetes were excluded from this trial (33).”
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    • cites [33] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med source

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    Premisecitation
    § Meta-analyses of Trials · p. 4

    One of the largest meta-analyses included 73,913 people with diabetes and found that tighter blood pressure control significantly reduced the risk of stroke by 31% but did not reduce the risk of myocardial infarction.

    “One of the largest meta-analyses included 73,913 people with diabetes. Compared with a less tight blood pressure control, allocation to a tighter blood pressure control signi fi cantly reduced the risk of stroke by 31% but did not reduce the risk of MI (38).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Reboldi, 2011, Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients, J Hypertens source

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    Premisecitation
    § Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control · p. 4

    In the STEP trial, 18.9% of patients in the intensive treatment arm and 19.4% in the standard treatment arm had a diagnosis of type 2 diabetes.

    “In this trial, 18.9% of patients in the intensive treatment arm and 19.4% in the standard treatment arm had a diagnosis of type 2 diabetes.”
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    • cites [34] Zhang, 2021, Trial of intensive blood-pressure control in older patients with hypertension, N Engl J Med source

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    Premisecitation
    § Recommendations · p. 8

    Lifestyle modification focusing on weight loss, Mediterranean or DASH eating pattern, reduction of saturated and trans fat, increased n-3 fatty acids, viscous fiber, plant stanols/sterols, and physical activity improves lipid profile and reduces ASCVD risk in people with diabetes.

    “Lifestyle modi fi cation focusing on weight loss (if indicated); application of a Mediterranean or Dietary Approaches to Stop Hypertension (DASH) eating pattern; reduction of saturated fat and trans fat; increase of dietary n-3 fatty acids, viscous fi ber, and plant stanols/sterols intake; and increased physical activity should be recommended to improve the lipid pro fi le and reduce the risk of d”
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    • cites [83] Mehdi, 2009, Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy, J Am Soc Nephrol source

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    • cites [86] Eckel, 2013, 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Circulation

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    • cites [87] Arnett, 2019, 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, Circulation

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    Premisecitation
    § Individualization of Treatment Targets · p. 6

    The American College of Obstetricians and Gynecologists recommends that postpartum individuals with gestational hypertension, preeclampsia, and superimposed preeclampsia have their blood pressures observed for 72 hours in the hospital and for 7-10 days postpartum.

    “The American College of Obstetricians and Gynecologists also recommends that postpartum individuals with gestational hypertension, preeclampsia, and superimposed preeclampsia have their blood pressures observed for 72 h in the hospital and for 7 -10 days postpartum.”
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    • cites [51] Irgens, 2001, Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study, BMJ source

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    Interpretationcitation
    § Individualization of Treatment Targets · p. 6

    Current evidence supports controlling blood pressure to 110-135/85 mmHg to reduce the risk of accelerated maternal hypertension while also minimizing impairment of fetal growth.

    “Current evidence supports controlling blood pressure to 110 -135/85 mmHg to reduce the risk of accelerated maternal hypertension but also to minimize impairment of fetal growth.”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Individualization of Treatment Targets · p. 6

    In CHIPS, the mean systolic blood pressure achieved in the more intensively treated group was 133.1 ± 0.5 mmHg, and the mean diastolic blood pressure achieved in that group was 85.3 ± 0.3 mmHg.

    “The mean systolic blood pressure achieved in the more intensively treated group was 133.1 ± 0.5 mmHg, and the mean diastolic blood pressure achieved in that group was 85.3 ± 0.3 mmHg.”
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    • cites [46] Magee, 2015, Less-tight versus tight control of hypertension in pregnancy, N Engl J Med source

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    § Recommendation · p. 6

    Lifestyle management lowers blood pressure, enhances the effectiveness of some antihypertensive medications, promotes other aspects of metabolic and vascular health, and generally leads to few adverse effects.

    “Lifestyle management is an important component of hypertension treatment because it lowers blood pressure, enhances the effectiveness of some antihypertensive medications, promotes other aspects of metabolic and vascular health, and generally leads to few adverse effects.”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Individualization of Treatment Targets · p. 6

    In CHIPS, targeting a diastolic blood pressure of 85 mmHg during pregnancy was associated with reduced likelihood of developing accelerated maternal hypertension and no demonstrable adverse outcome for infants compared with targeting a higher diastolic blood pressure.

    “In CHIPS, targeting a diastolic blood pressure of 85 mmHg during pregnancy was associated with reduced likelihood of developing accelerated maternal hypertension and no demonstrable adverse outcome for infants compared with targeting a higher diastolic blood pressure.”
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    • cites [46] Magee, 2015, Less-tight versus tight control of hypertension in pregnancy, N Engl J Med source

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    Premisecitation
    § Recommendations for the Treatment of Confirmed Hypertension in People With Diabetes · p. 8

    In people with diabetes, ACE inhibitors, ARBs, thiazide-like diuretics, and dihydropyridine calcium channel blockers reduce cardiovascular events.

    “Initial treatment for hypertension should include any of the drug classes demonstrated to reduce cardiovascular events in people with diabetes: ACE inhibitors (60,61), ARBs (60,61), thiazide-like diuretics (62), or dihydropyridine calcium channel blockers (63).”
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    • cites [60] Catalá-López, 2016, Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses, PLoS Med source

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    • cites [61] Palmer, 2015, Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis, Lancet source

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    • cites [62] Barzilay, 2004, Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study, J Clin Hypertens (Greenwich) source

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    • cites [63] Weber, 2010, Cardiovascular events during differing hypertension therapies in patients with diabetes, J Am Coll Cardiol source

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    Premisecitation
    § Individualization of Treatment Targets · p. 6

    Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and long-acting nifedipine, while hydralazine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia.

    “Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and long-acting nifedipine, while hydralzine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia (49).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy, 2013, Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy, Obstet Gynecol

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    Premisecitation
    § Individualization of Treatment Targets · p. 6

    The International Society for the Study of Hypertension in Pregnancy specifically recommends antihypertensive therapy to maintain systolic blood pressure between 110 and 140 mmHg and diastolic blood pressure between 80 and 85 mmHg.

    “A similar approach is supported by the International Society for the Study of Hypertension in Pregnancy, which speci fi cally recommends use of antihypertensive therapy to maintain systolic blood pressure between 110 and 140 mmHg and diastolic blood pressure between 80 and 85 mmHg (47).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Brown, 2018, Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice, Hypertension source

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    Premisecitation
    § Recommendations for the Treatment of Confirmed Hypertension in People With Diabetes · p. 8

    Diuretics can cause acute kidney injury and either hypokalemia or hyperkalemia depending on their mechanism of action.

    “Treatment with ACE inhibitors or ARBs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia (depending on mechanism of action) (77,78).”
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    • cites [77] Nilsson, 2017, Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system, Int J Cardiol source

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    • cites [78] Bandak, 2017, Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project, J Am Heart Assoc source

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    § Recommendations for the Treatment of Confirmed Hypertension in People With Diabetes · p. 8

    Acute kidney injury and hyperkalemia each increase the risks of cardiovascular events and death.

    “Detection and management of these abnormalities is important because AKI and hyperkalemia each increase the risks of cardiovascular events and death (79).”
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    • cites [79] Hughes-Austin, 2017, The relation of serum potassium concentration with cardiovascular events and mortality in community-living individuals, Clin J Am Soc Nephrol source

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    Premisecitation
    § Individualization of Treatment Targets · p. 5

    In ADVANCE, the intervention reduced the risk of the primary composite end point of major macrovascular and microvascular events by 9%, death from any cause by 14%, and death from cardiovascular disease by 18%.

    “Intervention reduced risk of primary composite end point of major macrovascular and microvascular events (9%), death from any cause (14%), and death from CVD (18%)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Patel, 2007, Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Recommendations for the Treatment of Confirmed Hypertension in People With Diabetes · p. 8

    Combining ACE inhibitors and ARBs, or combining an ACE inhibitor or ARB with a direct renin inhibitor, lacks added ASCVD benefit and increases hyperkalemia, syncope, and acute kidney injury.

    “However, the use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD bene fi t and increased rate of adverse events -namely, hyperkalemia, syncope, and acute kidney injury (AKI) (71 -73).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [71] Yusuf, 2008, Telmisartan, ramipril, or both in patients at high risk for vascular events, N Engl J Med source

      Not checked in the free run.

    • cites [72] Fried, 2013, Combined angiotensin inhibition for the treatment of diabetic nephropathy, N Engl J Med source

      Not checked in the free run.

    • cites [73] Makani, 2013, Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials, BMJ source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Recommendations for the Treatment of Confirmed Hypertension in People With Diabetes · p. 8

    Treatment with ACE inhibitors or ARBs can cause acute kidney injury and hyperkalemia.

    “Treatment with ACE inhibitors or ARBs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia (depending on mechanism of action) (77,78).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [77] Nilsson, 2017, Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system, Int J Cardiol source

      Not checked in the free run.

    • cites [78] Bandak, 2017, Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project, J Am Heart Assoc source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Recommendations · p. 10

    Meta-analyses including over 18,000 people with diabetes from 14 randomized statin trials demonstrate a 9% proportional reduction in all-cause mortality and 13% reduction in vascular mortality for each 1 mmol/L (39 mg/dL) reduction in LDL cholesterol.

    “Meta-analyses, including data from over 18,000 people with diabetes from 14 randomized trials of statin therapy (mean follow-up 4.3 years), demonstrate a 9% proportional reduction in all-cause mortality and 13% reduction in vascular mortality for each 1 mmol/L (39 mg/dL) reduction in LDL cholesterol (99).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [99] Kearney, 2008, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Secondary Prevention (People With ASCVD) · p. 10

    These large trials included a significant number of participants with diabetes and prespecified analyses on cardiovascular outcomes in people with and without diabetes.

    “These large trials included a signi fi cant number of participants with diabetes and prespeci fi ed analyses on cardiovascular outcomes in people with and without diabetes (109,111,112).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [109] Giugliano, 2018, Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), Circulation source

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    • cites [111] Ray, 2019, Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial, Lancet Diabetes Endocrinol source

      Not checked in the free run.

    • cites [112] Sabatine, 2017, Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial, Lancet Diabetes Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Statins and PCSK9 Inhibitors · p. 11

    In FOURIER, during median follow-up of 2.2 years, the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization occurred in 11.3% versus 9.8% of placebo and evolocumab groups, a 15% relative risk reduction.

    “During the median follow-up of 2.2 years, the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization occurred in 11.3% vs. 9.8% of the placebo and evolocumab groups, respectively, representing a 15% relative risk reduction (P < 0.001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Recommendations · p. 10

    In this meta-analysis, cardiovascular benefit did not depend on baseline LDL cholesterol and was linearly related to LDL cholesterol reduction without a low threshold beyond which no benefit was observed.

    “The cardiovascular bene fi t in this large meta-analysis did not depend on baseline LDL cholesterol levels and was linearly related to the LDL cholesterol reduction without a low threshold beyond which there was no bene fi t observed (99).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [99] Kearney, 2008, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Risk Reduction · p. 14

    In ASCEND, major bleeding increased from 3.2% to 4.1% with aspirin (rate ratio 1.29; P=0.003), mostly GI and other extracranial.

    “In contrast, major bleeding was signi fi cantly increased from 3.2 to 4.1% in the aspirin group (rate ratio 1.29; P = 0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] ASCEND Study Collaborative Group, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Recommendations · p. 10

    Absolute reductions in ASCVD outcomes are greatest in people with high baseline ASCVD risk, but overall benefits of statin therapy in people with diabetes at moderate or even low risk are convincing.

    “As in those without diabetes, absolute reductions in ASCVD outcomes (CHD death and nonfatal MI) are greatest in people with high baseline ASCVD risk (known ASCVD and/or very high LDL cholesterol levels), but the overall benefi ts of statin therapy in people with diabetes at moderate or even low risk for ASCVD are convincing (100,101).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [100] Taylor, 2013, Statins for the primary prevention of cardiovascular disease, Cochrane Database Syst Rev

      Not checked in the free run.

    • cites [101] Carter, 2013, Risk of incident diabetes among patients treated with statins: population based study, BMJ source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Secondary Prevention (People With ASCVD) · p. 10

    Cardiovascular event rates are increased in people with diabetes and established ASCVD, and intensive therapy has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials.

    “Because cardiovascular event rates are increased in people with diabetes and established ASCVD, intensive therapy is indicated and has been shown to be of bene fi t in multiple large meta-analyses and randomized cardiovascular outcomes trials (91,99,105,107,108).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [91] Baigent, 2005, Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins, Lancet source

      Not checked in the free run.

    • cites [99] Kearney, 2008, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet source

      Not checked in the free run.

    • cites [105] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

      Not checked in the free run.

    • cites [107] Cannon, 2004, Intensive versus moderate lipid lowering with statins after acute coronary syndromes, N Engl J Med source

      Not checked in the free run.

    • cites [108] Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning
    § Recommendations · p. 10

    Statins are the drugs of choice for LDL cholesterol lowering and cardioprotection.

    “Accordingly, statins are the drugs of choice for LDL cholesterol lowering and cardioprotection.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Combination Therapy for LDL Cholesterol Lowering · p. 11

    In IMPROVE-IT, addition of ezetimibe to simvastatin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events, with benefit directly proportional to LDL cholesterol change.

    “Overall, the addition of ezetimibe led to a 6.4% relative bene fi t and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of bene fi t being directly proportional to the change in LDL cholesterol, which was 70 mg/dL in the statin group on average and 54 mg/dL in the combination group (105).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [105] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Risk Reduction · p. 14

    In ASCEND, no significant differences in effects by sex, weight, diabetes duration, or other baseline factors including ASCVD risk score.

    “There were no signi fi cant differences by sex, weight, or duration of diabetes or other baseline factors including ASCVD risk score.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [144] ASCEND Study Collaborative Group, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Statins and PCSK9 Inhibitors · p. 11

    In FOURIER, evolocumab significantly reduced all strokes and ischemic stroke, with findings consistent in individuals with or without a history of ischemic stroke at baseline.

    “Evolocumab therapy also signi fi cantly reduced all strokes (1.5% vs. 1.9%; HR 0.79 [95% CI 0.66 -0.95]; P = 0.01) and ischemic stroke (1.2% vs. 1.6%; HR 0.75 [95% CI 0.62 -0.92]; P = 0.005) in the total population, with fi ndings being consistent in individuals with or without a history of ischemic stroke at baseline (115).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] Giugliano, 2020, Stroke prevention with the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis, Stroke source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Indications for P2Y12 Receptor Antagonist Use · p. 15

    Net clinical benefit was improved with ticagrelor in patients with history of PCI, while no net benefit was seen in patients without prior PCI.

    “The net clinical bene fi t (ischemic bene fi t vs. bleeding risk) was improved with ticagrelor therapy in the large prespecifi ed subgroup of patients with history of percutaneous coronary intervention, while no net benefi t was seen in patients without prior percutaneous coronary intervention (165).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Bhatt, 2019, Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial, Lancet source

      Not checked in the free run.

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

    Premisecitation
    § Aspirin Dosing · p. 14

    A trial suggested more frequent aspirin dosing may reduce platelet reactivity in individuals with diabetes.

    “A trial suggested that more frequent dosing regimens of aspirin may reduce platelet reactivity in individuals with diabetes (160); however, these observations alone are insuf fi cient to empirically recommend that higher doses of aspirin be used in this group at this time.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [160] Bethel, 2016, Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with type 2 diabetes, Diabet Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation
    § Aspirin Dosing · p. 14

    A meta-analysis raised the hypothesis that low-dose aspirin efficacy is reduced in people weighing >70 kg.

    “Another meta-analysis raised the hypothesis that low-dose aspirin ef fi cacy is reduced in those weighing > 70 kg (161); however, the ASCEND trial found bene fi t of low-dose aspirin in those in this weight range, which would thus not validate this suggested hypothesis (144).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [161] Rothwell, 2018, Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Glucose-Lowering Therapies and Cardiovascular Outcomes · p. 20

    In CAROLINA, linagliptin was noninferior to glimepiride for cardiovascular outcomes and caused less hypoglycemia.

    “In addition, the CAROLINA (Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Type 2 Diabetes) study demonstrated noninferiority between a DPP-4 inhibitor, linagliptin, and a sulfonylurea, glimepiride, on cardiovascular outcomes despite lower rates of hypoglycemia in the linagliptin treatment group (193).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [193] Rosenstock, 2019, Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 20

    In the combined CANVAS Program analysis, canagliflozin reduced the composite of cardiovascular death, myocardial infarction, or stroke compared with placebo, with 26.9 versus 31.5 events per 1,000 patient-years and a hazard ratio of 0.86 (95% CI 0.75-0.97).

    “The combined analysis of the two trials found that canagli fl ozin signi fi cantly reduced the composite outcome of cardiovascular death, MI, or stroke versus placebo (occurring in 26.9 vs. 31.5 participants per 1,000 patient-years; HR 0.86 [95% CI 0.75 -0.97]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Aspirin Dosing · p. 14

    The ASCEND trial found benefit of low-dose aspirin in people weighing >70 kg, not validating the hypothesis of reduced efficacy.

    “Another meta-analysis raised the hypothesis that low-dose aspirin ef fi cacy is reduced in those weighing > 70 kg (161); however, the ASCEND trial found bene fi t of low-dose aspirin in those in this weight range, which would thus not validate this suggested hypothesis (144).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] ASCEND Study Collaborative Group, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Aspirin Dosing · p. 14

    In ADAPTABLE, cardiovascular events and major bleeding did not differ significantly between aspirin 81 mg and 325 mg daily.

    “In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefi ts and Long-term Effectiveness) trial of individuals with established cardiovascular disease, 38% of whom had diabetes, there were no signi fi cant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily (156).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [156] Jones, 2021, Comparative effectiveness of aspirin dosing in cardiovascular disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Risk Reduction · p. 14

    Aspirin has a modest effect on ischemic vascular events, with absolute decrease depending on underlying ASCVD risk.

    “Thus, aspirin appears to have a modest effect on ischemic vascular events, with the absolute decrease in events depending on the underlying ASCVD risk.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Screening Asymptomatic Patients · p. 19

    Among asymptomatic people with type 2 diabetes and normal ECGs, although over one in five had abnormal myocardial perfusion imaging, screened and unscreened groups had similar and very low cardiac outcomes.

    “Despite abnormal myocardial perfusion imaging in more than one in fi ve patients, cardiac outcomes were essentially equal (and very low) in screened versus unscreened patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [178] Young, 2009, Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial, JAMA source

      Not checked in the free run.

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

    Interpretationreasoning
    § Glucose-Lowering Therapies and Cardiovascular Outcomes · p. 19

    The FDA guidance did not apply to diabetes medications already approved.

    “Previously approved diabetes medications were not subject to the guidance.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation
    § SGLT2 Inhibitor Trials · p. 20

    The CANVAS trial was partially unblinded before it finished because interim cardiovascular outcome data had to be filed for regulatory approval.

    “The CANVAS trial that started in 2009 was partially unblinded prior to completion because of the need to fi le interim cardiovascular outcomes data for regulatory approval of the drug (195).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [195] Neal, 2017, Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial, Diabetes Obes Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Indications for P2Y12 Receptor Antagonist Use · p. 15

    Evidence supports use of either ticagrelor or clopidogrel if no PCI, and clopidogrel, ticagrelor, or prasugrel if PCI.

    “Evidence supports use of either ticagrelor or clopidogrel if no percutaneous coronary intervention was performed and clopidogrel, ticagrelor , or prasugrel if a percutaneous coronary intervention was performed (162).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Vandvik, 2012, Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Screening Asymptomatic Patients · p. 19

    In people with diabetes, coronary artery calcium independently predicts future ASCVD events and outperforms the UKPDS and Framingham risk scores for risk prediction.

    “In prospective studies, coronary artery calcium has been established as an independent predictor of future ASCVD events in people with diabetes and is consistently superior to both the UK Prospective Diabetes Study (UKPDS) risk engine and the Framingham Risk Score in predicting risk in this population (175 -177).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [175] Elkeles, 2008, Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study, Eur Heart J source

      Not checked in the free run.

    • cites [176] Raggi, 2004, Prognostic value of coronary artery calcium screening in subjects with and without diabetes, J Am Coll Cardiol source

      Not checked in the free run.

    • cites [177] Anand, 2006, Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy, Eur Heart J source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 23

    In DAPA-CKD, the effects of dapagliflozin were similar in individuals with and without type 2 diabetes.

    “The effects of dapagli fl ozin therapy were similar in individuals with and without type 2 diabetes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [197] Heerspink, 2020, Dapagliflozin in patients with chronic kidney disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation
    § SGLT2 Inhibitor Trials · p. 20

    The CREDENCE trial was stopped early because a prespecified interim analysis found conclusive efficacy and no unexpected safety signals.

    “The trial was stopped early due to conclusive evidence of ef fi cacy identi fi ed during a prespeci fi ed interim analysis with no unexpected safety signals.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 23

    In SCORED, there were no significant between-group differences for all-cause mortality or for a composite renal outcome of long-term dialysis, renal transplantation, or sustained eGFR reduction.

    “No signi fi cant between-group differences were found for the outcome of all-cause mortality or for a composite renal outcome comprising the fi rst occurrence of long-term dialysis, renal transplantation, or a sustained reduction in eGFR.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [202] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 23

    Sotagliflozin's adverse effects were generally similar to those of SGLT2 inhibitors, but included an increased rate of diarrhea potentially related to SGLT1 inhibition.

    “In general, the adverse effects of sotagli fl ozin were similar to those seen with use of SGLT2 inhibitors, but they also included an increased rate of diarrhea potentially related to the inhibition of SGLT1.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [202] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 24

    In ELIXA, the primary outcome occurred in 13.4% of lixisenatide patients and 13.2% of placebo patients (HR 1.2, 95% CI 0.89-1.17).

    “The primary outcome of cardiovascular death, MI, stroke, or hospitalization for unstable angina occurred in 406 patients (13.4%) in the lixisenatide group vs. 399 (13.2%) in the placebo group (HR 1.2 [95% CI 0.89 -1.17]), which demonstrated the noninferiority of lixisenatide to placebo ( P < 0.001) but did not show superiority ( P = 0.81).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [208] Pfeffer, 2015, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 20

    In CREDENCE, canagliflozin increased the risk of diabetic ketoacidosis, with 2.2 versus 0.2 events per 1,000 patient-years and a hazard ratio of 10.80 (95% CI 1.39-83.65).

    “An increased risk for diabetic ketoacidosis was noted, however, with 2.2 and 0.2 events per 1,000 patient-years noted in the canagli fl ozin and placebo groups, respectively (HR 10.80 [95% CI 1.39 -83.65]) (194).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 23

    Ertugliflozin was not superior to placebo for the key secondary outcomes of cardiovascular death or hospitalization for heart failure, cardiovascular death, or the composite of renal death, renal replacement therapy, or doubling of serum creatinine.

    “Ertugli fl ozin was not superior to placebo for the key secondary outcomes of death from cardiovascular causes or hospitalization for heart failure; death from cardiovascular causes; or the composite of death from renal causes, renal replacement therapy, or doubling of the serum creatinine level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [201] Cannon, 2020, Cardiovascular outcomes with ertugliflozin in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 20

    In CREDENCE, canagliflozin did not significantly increase lower-limb amputations, fractures, acute kidney injury, or hyperkalemia compared with placebo.

    “In terms of safety, no signi fi cant increase in lower-limb amputations, fractures, acute kidney injury, or hyperkalemia was noted for canaglifl ozin relative to placebo in CREDENCE.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation
    § SGLT2 Inhibitor Trials · p. 23

    In DAPA-CKD, dapagliflozin lowered the risk of the composite of cardiovascular death or hospitalization for heart failure (HR 0.71, 95% CI 0.55-0.92).

    “or hospitalization for heart failure (HR 0.71 [95% CI 0.55 -0.92]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [197] Heerspink, 2020, Dapagliflozin in patients with chronic kidney disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation
    § SGLT2 Inhibitor Trials · p. 23

    SCORED ended early because of lack of funding, and its prespecified primary endpoints were changed before unblinding to accommodate fewer endpoint events than anticipated.

    “SCORED ended early due to a lack of funding; thus, changes to the prespeci fi ed primary end points were made prior to unblinding to accommodate a lower than anticipated number of end point events.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [202] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 24

    In EXSCEL, the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the exenatide and placebo groups.

    “The incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ signi fi cantly between the two groups.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [209] Holman, 2017, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 24

    In EXSCEL, extended-release exenatide produced numerically lower major adverse cardiovascular events than placebo, but the difference was not statistically significant.

    “The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial also reported results with the once-weekly GLP-1 receptor agonist extended-release exenatide and found that major adverse cardiovascular events were numerically lower with use of extended-release exenatide compared with placebo, although this difference was not statistically signi fi cant (209).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Holman, 2017, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 24

    In AMPLITUDE-O, over a median follow-up of 1.8 years, efpeglenatide reduced the risk of incident major adverse cardiovascular events by 27% and of a composite renal outcome event by 32%.

    “Over a median follow-up of 1.8 years, efpeglenatide therapy reduced the risk of incident major adverse cardiovascular events by 27% and of a composite renal outcome event by 32%.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [214] Gerstein, 2021, Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation
    § GLP-1 Receptor Agonist Trials · p. 25

    EMPEROR-Preserved was a randomized double-blinded placebo-controlled trial of 5,988 adults with NYHA class I-IV chronic HFpEF and left ventricular ejection fraction >40%, evaluating empagliflozin 10 mg daily versus placebo on top of standard care.

    “EMPEROR-Preserved, a randomized double-blinded placebo-controlled trial of 5,988 adults with NYHA functional class I -IV chronic HFpEF (left ventricular ejection fraction > 40%), evaluated the ef fi cacy of empagli fl ozin 10 mg daily versus placebo on top of standard of care on the primary outcome of composite cardiovascular death or hospitalization for heart failure (189).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [189] Anker, 2021, Empagliflozin in heart failure with a preserved ejection fraction, N Engl J Med source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 26

    In the same heart failure population, empagliflozin reduced total hospitalizations for heart failure requiring intensive care, a vasopressor or positive inotropic drug, or mechanical or surgical intervention.

    “In 3,730 patients with NYHA class II -IV heart failure with an ejection fraction of # 40%, treatment with empagli fl ozin reduced the combined risk of death, hospitalization for heart failure, or an emergent/urgent heart failure visit requiring intravenous treatment and reduced the total number of hospitalizations for heart failure requiring intensive care, a vasopressor or positive inotropic drug”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [229] Packer, 2021, Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial, Circulation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 25

    The meta-analysis findings were consistent in trials of heart failure with mildly reduced or preserved ejection fraction and in all five trials combined.

    “The fi ndings on the studied end points were consistent in both trials of heart failure with mildly reduced or preserved ejection fraction and in all fi ve trials combined.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [227] Vaduganathan, 2022, SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 24

    SGLT2 inhibitors reduce the risk of heart failure hospitalization and progression of kidney disease in people with established ASCVD, multiple ASCVD risk factors, or albuminuric kidney disease.

    “SGLT2 inhibitors also reduce risk of heart failure hospitalization and progression of kidney disease in people with established ASCVD, multiple risk factors for ASCVD, or albuminuric kidney disease (212,213).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [212] Zelniker, 2019, SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials, Lancet source

      Not checked in the free run.

    • cites [213] McGuire, 2021, Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis, JAMA Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data
    § GLP-1 Receptor Agonist Trials · p. 26

    In SOLOIST-WHF, there were no significant between-group differences in cardiovascular death or all-cause mortality.

    “No signi fi cant between-group differences were found in the rates of cardiovascular death or all-cause mortality.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [228] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § GLP-1 Receptor Agonist Trials · p. 25

    Collectively, the studies indicate that SGLT2 inhibitors reduce the risk for heart failure hospitalization and cardiovascular death across a wide range of people with heart failure.

    “Collectively, these studies indicate that SGLT2 inhibitors reduce the risk for heart failure hospitalization and cardiovascular death in a wide range of people with heart failure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 24

    Numerous large randomized controlled trials report statistically significant reductions in cardiovascular events for three FDA-approved SGLT2 inhibitors: empagliflozin, canagliflozin, and dapagliflozin, with lesser benefits seen with ertugliflozin.

    “In summary, there are now numerous large randomized controlled trials reporting statistically signi fi cant reductions in cardiovascular events for three of the FDA-approved SGLT2 inhibitors (empagli fl ozin, canagli fl ozin, dapagli fl ozin, with lesser bene fi ts seen with ertugli fl ozin)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

      Not checked in the free run.

    • cites [196] Wiviott, 2019, Dapagliflozin and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation
    § GLP-1 Receptor Agonist Trials · p. 26

    In SOLOIST-WHF, the small percentage of HFpEF patients and early trial termination limited the ability to determine the effects of sotagliflozin specifically in HFpEF.

    “However, the relatively small percentage of such patients enrolled (only 21% of participants had ejection fraction > 50%) and the early termination of the trial limited the ability to determine the effects of sotagli fl ozin in HFpEF speci fi cally.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [228] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 26

    In SOLOIST-WHF, among 1,222 people with type 2 diabetes recently hospitalized for worsening heart failure, sotagliflozin reduced primary endpoint events compared with placebo (51.0 vs 76.3; HR 0.67).

    “At a median follow-up of 9 months, the rate of primary end point events (the total number of cardiovascular deaths and hospitalizations and urgent visits for heart failure) was lower in the sotaglifl ozin group than in the placebo group (51.0 vs. 76.3; HR 0.67 [95% CI 0.52 -0.85]; P < 0.001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [228] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 25

    In CREDENCE, canagliflozin reduced heart failure hospitalization by 39% and the composite of cardiovascular death or heart failure hospitalization by 31% in a diabetic kidney disease population with albuminuria (UACR >300 to 5,000 mg/g).

    “Additional data from the CREDENCE trial with canagli fl ozin showed a 39% reduction in hospitalization for heart failure, and 31% reduction in the composite of cardiovascular death or hospitalization for heart failure, in a diabetic kidney disease population with albuminuria (UACR > 300 to 5,000 mg/g) (194).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § GLP-1 Receptor Agonist Trials · p. 25

    In CANVAS and DECLARE-TIMI 58, SGLT2 inhibitor use versus placebo reduced heart failure hospitalization by 33% and 27%, respectively.

    “Similarly, in CANVAS and DECLARE-TIMI 58, there were 33% and 27% reductions in hospitalization for heart failure, respectively, with SGLT2 inhibitor use versus placebo (9,196).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [196] Wiviott, 2019, Dapagliflozin and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Finerenone in People With Type 2 Diabetes and Chronic Kidney Disease · p. 26

    People with diabetes are at increased risk for chronic kidney disease, which increases cardiovascular risk.

    “As discussed in detail in Section 11, ' Chronic Kidney Disease and Risk Management, ' people with diabetes are at an increased risk for CKD, which increases cardiovascular risk (232).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [232] Gansevoort, 2013, Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Finerenone in People With Type 2 Diabetes and Chronic Kidney Disease · p. 26

    A prespecified FIGARO-DKD subgroup analysis found that in patients without symptomatic HFrEF, finerenone reduces the risk for new-onset heart failure and improves heart failure outcomes in people with type 2 diabetes and CKD.

    “A prespeci fi ed subgroup analysis from FIGARO-DKD further revealed that in patients without symptomatic HFrEF, fi nerenone reduces the risk for new-onset heart failure and improves heart failure outcomes in people with type 2 diabetes and CKD (187).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [187] Filippatos, 2022, Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial, Circulation source

      Not checked in the free run.

84 of 84

  • The paper relies on this without support.

    Common conditions coexisting with type 2 diabetes, such as hypertension and dyslipidemia, are risk factors for ASCVD, and diabetes itself confers independent risk.

    “Common conditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for ASCVD, and diabetes itself confers independent risk.”

  • The paper relies on this without support.

    The majority of evidence supporting interventions to reduce cardiovascular risk in diabetes comes from trials of people with type 2 diabetes.

    “Notably, the majority of evidence supporting interventions to reduce cardiovascular risk in diabetes comes from trials of people with type 2 diabetes.”

  • The paper relies on this without support.

    No randomized trials have been specifically designed to assess the impact of cardiovascular risk reduction strategies in people with type 1 diabetes.

    “No randomized trials have been speci fi cally designed to assess the impact of cardiovascular risk reduction strategies in people with type 1 diabetes.”

  • The paper relies on this without support.

    Hypertension is common among people with either type 1 or type 2 diabetes.

    “Hypertension is common among people with either type 1 or type 2 diabetes.”

  • The paper relies on this without support.

    Hypertension is a major risk factor for both ASCVD and microvascular complications.

    “Hypertension is a major risk factor for both ASCVD and microvascular complications.”

  • The paper relies on this without support.

    In the absence of albuminuria, the risk of progressive kidney disease is low.

    “In the absence of albuminuria, risk of progressive kidney disease is low, and ACE inhibitors and ARBs have not been found to afford superior cardioprotection when compared with thiazide-like diuretics or dihydropyridine calcium channel blockers (68).”

  • The paper relies on this without support.

    Multiple-drug therapy is often required to achieve blood pressure targets, particularly in diabetic kidney disease.

    “Multiple-drug therapy is often required to achieve blood pressure targets ( Fig. 10.2 ), particularly in the setting of diabetic kidney disease.”

  • The paper relies on this without support.

    Adding a mineralocorticoid receptor antagonist to a regimen including an ACE inhibitor or ARB may increase the risk for hyperkalemia.

    “However, adding a mineralocorticoid receptor antagonist to a regimen including an ACE inhibitor or ARB may increase the risk for hyperkalemia, emphasizing the importance of regular monitoring for serum creatinine and potassium in these patients, and long-term outcome studies are needed to better evaluate the role of mineralocorticoid receptor antagonists in blood pressure management.”

  • The paper relies on this without support.

    Glycemic control may beneficially modify plasma lipid levels, particularly in patients with very high triglycerides and poor glycemic control.

    “Glycemic control may also bene fi cially modify plasma lipid levels, particularly in patients with very high triglycerides and poor glycemic control.”

  • The paper relies on this without support.

    People with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of ASCVD.

    “People with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of ASCVD.”

  • The paper relies on this without support.

    Cardiovascular risk is enhanced in people with diabetes.

    “Since cardiovascular risk is enhanced in people with diabetes, as noted above, patients who also have multiple other coronary risk factors have increased risk, equivalent to that of those with ASCVD.”

  • The paper relies on this without support.

    Patients with diabetes and multiple other coronary risk factors have increased risk equivalent to that of those with ASCVD.

    “Since cardiovascular risk is enhanced in people with diabetes, as noted above, patients who also have multiple other coronary risk factors have increased risk, equivalent to that of those with ASCVD.”

  • The paper relies on this without support.

    Patients under 40 years of age have lower 10-year cardiovascular risk but high lifetime risk of cardiovascular disease and events.

    “Patients < 40 years of age have lower risk of developing a cardiovascular event over a 10-year horizon; however, their lifetime risk of developing cardiovascular disease and suffering an MI, stroke, or cardiovascular death is high.”

  • The paper relies on this without support.

    Aspirin is associated with Reye syndrome in people younger than 21 years, which makes its use generally contraindicated in that age group.

    “Aspirin use in patients aged < 21 years is generally contraindicated due to the associated risk of Reye syndrome.”

  • The paper relies on this without support.

    Platelet function is altered in people with diabetes.

    “Although platelets from people with diabetes have altered function, it is unclear what, if any, effect that fi nding has on the required dose of aspirin for cardioprotective effects in people with diabetes.”

  • The paper relies on this without support.

    In clinical trials of people with diabetes, average daily aspirin doses ranged from 50 to 650 mg, mostly 100-325 mg/day.

    “Average daily dosages used in most clinical trials involving people with diabetes ranged from 50 mg to 650 mg but were mostly in the range of 100 -325 mg/day.”

  • The paper relies on this without support.

    No randomized trial of metformin therapy has been conducted in people with heart failure.

    “however, no randomized trial of metformin therapy has been conducted in people with heart failure.”

  • The paper relies on this without support.

    Most patients enrolled in the relevant trials were receiving metformin at baseline as glucose-lowering therapy.

    “' Most patients enrolled in the relevant trials were on metformin at baseline as glucose-lowering therapy.”

  • The authors state this as an assumption.

    Peripheral artery disease is assumed to be atherosclerotic in origin.

    “*ASCVD is defined as a history of an acute coronary syndrome or MI, stable or unstable angina, coronary heart disease with or without revascularization, other arterial revascularization, stroke, or peripheral artery disease assumed to be atherosclerotic in origin.”
19 of 19

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?

  • Current guidelines recommend the use of GLP-1 receptor agonists in patients with diabetes who need cardiovascular risk reduction, weight management, or both.

    “and current guidelines recommend the use of GLP-1 receptor agonists in patients with diabetes who need cardiovascular risk reduction, weight management, or both. 38,39”

    From Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (2023) · cites this paper as [38]

    The Recommendations (p. 15) recommend a GLP-1 receptor agonist with demonstrated cardiovascular benefit for cardiovascular risk reduction in people with type 2 diabetes and established atherosclerotic cardiovascular or kidney disease. The cited section does not recommend GLP-1 receptor agonists for weight management; its weight-loss recommendations concern lifestyle interventions (Recommendations, p. 8). The claim also omits the guideline’s type 2 diabetes and cardiovascular-risk qualifications. (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.

  • ACCORD BP standard-group systolic pressure differs between text and table

    Minor

    The text reports an achieved mean systolic pressure of 133 mmHg for the standard group, whereas the table reports 135 mmHg.

  • REWIND participant counts disagree

    Minor

    The narrative gives approximately 9,990 participants, while the trial table lists 9,901-a difference of 89 people.

  • ELIXA hazard ratio lies outside its reported confidence interval

    Minor

    The stated hazard ratio of 1.2 exceeds the upper limit of its own 95% confidence interval, 1.17.

3 of 3

Cites

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12 of the 265 references couldn’t be matched to a known paper.

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Related

Authors
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Das, S. R., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Kosiborod, M., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., Seley, J. J., Stanton, R. C., & Gabbay, R. A.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2022-12-12
Volume
46
Issue
Supplement_1
Pages
S158-S190
ISSN
0149-5992 (ISSN-L)
DOI
10.2337/dc23-s010
PMC
PMC9810475
OpenAlex
W4311263985
Cited by
465
References
265
Citations by year
2026: 43 · 2025: 104 · 2024: 186 · 2023: 132
FWCI
15.01
Type
journal article
Language
en
Update notices
correction (2023-01-26)
Open access
Licence
www.diabetesjournals.org/journals/pages/license (vor)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
cardiovascular disease, diabetes mellitus, cardiovascular risk management, clinical guidelines, quality of care, treatment goals
MeSH terms
Cardiovascular Diseases, Diabetes Mellitus, Endocrinology, Humans, Reference Standards, Societies, Medical, Standard of Care

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 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

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.

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