The DOI matches its Crossref record; 43 of the 47 references it cites were found in a registry or an index; 5 of the 50 sources its claims cite were checked for support.
Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review
Open accessAbstract
Importance: Recent randomized clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in at-risk individuals with type 2 diabetes. Despite these findings, GLP-1RAs are underused in eligible patients, particularly by cardiologists. Observations: To date, randomized clinical trials of albiglutide, dulaglutide, liraglutide, and injectable semaglutide have reported favorable cardiovascular outcomes. Most recently approved for clinical use, oral semaglutide has a favorable safety profile and is currently undergoing regulatory evaluation and further study for cardiovascular outcomes. Professional society guidelines now recommend GLP-1RA therapy for cardiovascular risk mitigation in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors, independent of glucose control or background antihyperglycemic therapy (other diabetes medications being used). Additional conditions suitable for GLP-1RA therapy include obesity and advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), for which cardiovascular risk-reducing options are limited. Out-of-pocket costs and secondary advantages (eg, weight loss) may inform shared decision-making discussions regarding potential therapies. GLP-1RA therapy has a favorable safety profile. Its most common adverse effect is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated. Depending on baseline glycemic control, sulfonylureas and insulin may need to be decreased before GLP-1RA initiation; without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia. Multidisciplinary follow-up and collaborative care with primary care physicians and/or endocrinologists are important. Conclusions and Relevance: Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists. This review provides a practical resource for cardiologists for initiating GLP-1RAs and managing the therapy in patients with type 2 diabetes and established ASCVD or high risk for ASCVD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
GLP-1 receptor agonists are safe, well tolerated, and improve cardiovascular outcomes in patients with type 2 diabetes, largely independent of glycemic control, but remain underused by cardiologists. This review provides practical guidance for cardiologists on initiating and managing GLP-1RA therapy in patients with established ASCVD or high ASCVD risk.
Key findings
- Across cardiovascular outcomes trials, GLP-1RAs reduced mean relative risk of MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by albuminuria improvements).
- Uptake is low: less than 8% of individuals with type 2 diabetes and ASCVD received GLP-1RA prescriptions in 2 US observational studies, and less than 5% of GLP-1RA prescriptions in tertiary care centers were attributable to cardiologists.
- Safety and tolerability: gastrointestinal upset occurs in 15% to 40% of patients within the first 4 weeks and is typically transient; hypoglycemia is rare without concurrent insulin or sulfonylureas; weight loss was 1.5 to 4.3 kg in trials with follow-up of 1.3 to 5.4 years.
- Special considerations include use of liraglutide, dulaglutide, and injectable semaglutide in advanced CKD at any eGFR without dose adjustment; albiglutide reduced HF hospitalization (HR, 0.71; 95% CI, 0.53–0.94; P < .001); and injectable semaglutide was associated with retinopathy complications in SUSTAIN-6 (3.0% vs 1.8%).
Methods
- Narrative/practical review for cardiologists; PubMed was searched for English-language studies published January 1, 2005, to October 31, 2019, identifying 7 cardiovascular outcomes trials of GLP-1RA therapy; the search was conducted August 1, 2019, to October 31, 2019.
- Evidence was synthesized from primary trial publications, key secondary analyses, summary meta-analyses, US Food and Drug Administration labels, and professional society guidelines.
- The review focuses on marketed GLP-1RAs with FDA indications for cardiovascular risk reduction: liraglutide, dulaglutide, and injectable semaglutide.
Limitations
- Stated in the paper: data are limited for GLP-1RA use in end-stage kidney disease (eGFR <15 mL/min/1.73 m²), HF subtype data are lacking, head-to-head cardiovascular outcome trials between GLP-1RAs and SGLT2 inhibitors are absent, and data on incremental cardiovascular advantage of concurrent GLP-1RA plus SGLT2 inhibitor use are lacking.
- Stated in the paper: oral semaglutide and efpeglenatide cardiovascular outcomes were still being assessed, and comparative cost-effectiveness/value studies are needed.
- Evident from the text: this is a narrative review without systematic review or meta-analysis methods, relies on a PubMed-only English-language search through October 2019, and reports no new primary patient data.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
30 Not checked yet · 11 No basis given · 3 Own interpretation · 2 Partly supported · 1 Mixed support · 1 Own method · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent randomized clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in at-risk individuals with type 2 diabetes.”
- Also stated in: § Observations · boosted
“Among commercially available GLP-1RAs, reduction in MACE has been demonstrated in randomized clinical trials of once-daily dosed liraglutide6 and 3 once-weekly injections of GLP-1RAs:semaglutide,7 albiglutide,8 and dulaglutide.9”
- Also stated in: § CONCLUSIONS AND RELEVANCE · hedged
“Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > IMPORTANCE
What the sources say
- Partly supportedcites [6] Marso SP, Daniels GH, Brown-Frandsen K,; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375(4): 311– 322.doi: 10.1056/NEJMoa1603827 27295427 PMC4985288 sourceExperimental — accuracy not yet measured
The Discussion (page not specified) reports fewer cardiovascular events with liraglutide than with placebo in patients with type 2 diabetes at high cardiovascular risk. This supports the claim for liraglutide, but not for GLP-1RAs as a class: the same section says a trial of another GLP-1RA, lixisenatide, found no cardiovascular benefit. (LLM, conf=0.88)
- Supportedcites [7] Marso SP, Bain SC, Consoli A,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source
The Conclusions report significantly fewer composite cardiovascular events with semaglutide than with placebo in patients with type 2 diabetes at high cardiovascular risk. The same passage also reports improved cardiovascular outcomes in an earlier liraglutide trial, supporting the sentence’s plural reference to GLP-1 receptor agonist trials. The reduction concerns the composite outcome, not cardiovascular death alone. (LLM, conf=0.90)
- Not checked yetcites [9] Gerstein HC, Colhoun HM, Dagenais GR,; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394 (10193): 121– 130. doi: 10.1016/S0140-6736(19)31149-3 31189511 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Observations · boosted
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering) trial, risk reduction in mortality and HF hospitalization outcomes appeared restricted to patients without prevalent HF.33”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
What the sources say
- Partly supportedcites [33] Fudim M, White J, Pagidipati NJ, Effect of once-weekly exenatide in patients with type 2 diabetes mellitus with and without heart failure and heart failure-related outcomes: insights from the EXSCEL trial. Circulation. 2019; 140(20): 1613– 1622. doi: 10.1161/CIRCULATIONAHA.119.041659 31542942 PMC6924268 sourceExperimental — accuracy not yet measured
The Results (Preexisting Heart Failure – Baseline Characteristics and Outcomes; page unavailable) report that reductions in all-cause mortality and the composite of all-cause death or HF hospitalization appeared only in patients without baseline HF. But the Results (Hospitalization for Heart Failure During Follow-up; page unavailable) found no interaction by baseline HF status for first plus recurrent HF hospitalizations. The claim is supported for mortality and the composite outcome, not for HF hospitalization considered separately. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
In the paper
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists.”
- Also stated in: § Observations · boosted
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Observations · boosted
In the paper
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“GLP-1RA therapy has a favorable safety profile.”
- Also stated in: § Observations · plain
“In addition, GLP-1RAs have a favorable safety profile and have been associated with substantial weight loss.4,6,7,9”
- Also stated in: § CONCLUSIONS AND RELEVANCE · hedged
“Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > OBSERVATIONS
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
- Not checked yetcites [6] Marso SP, Daniels GH, Brown-Frandsen K,; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375(4): 311– 322.doi: 10.1056/NEJMoa1603827 27295427 PMC4985288 source
- Not checked yetcites [7] Marso SP, Bain SC, Consoli A,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The most common adverse effect of GLP-1RA therapy is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated.
- Rests on an assumption: Without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia.
- Also stated in: § Observations · plain
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, GLP-1RAs have a favorable safety profile and have been associated with substantial weight loss.4,6,7,9”
- Also stated in: § Special Considerations · plain
“As a class of antihyperglycemic medications, GLP-1RAs were associated with substantial weight loss of 1.5 to 4.3 kg in trials with follow-up of 1.3 to 5.4 years,6,7,9,29 making these agents desirable when weight loss is a priority.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [6] Marso SP, Daniels GH, Brown-Frandsen K,; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375(4): 311– 322.doi: 10.1056/NEJMoa1603827 27295427 PMC4985288 source
- Not checked yetcites [7] Marso SP, Bain SC, Consoli A,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source
- Not checked yetcites [9] Gerstein HC, Colhoun HM, Dagenais GR,; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394 (10193): 121– 130. doi: 10.1016/S0140-6736(19)31149-3 31189511 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Special Considerations · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Specifically, SGLT2 inhibitors are currently contraindicated in patients with a preinitiation eGFR less than 30 mL/min/1.73 m2; patients with established ASCVD and an eGFR below this threshold may be good candidates for GLP-1RA therapy.”
- Also stated in: § Secondary Benefits · hedged
“However, data are limited on antihyperglycemic therapies associated with reduced risk of cardiovascular disease in individuals with more advanced CKD, and use of all SGLT2 inhibitors is currently discouraged for those with an eGFR less than 30 mL/min/1.73 m2.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Secondary Benefits · hedged
In the paper
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In the US, the 2020 national median drug acquisition cost of GLP-1RAs ranges from $634 per month to $835 per month,27·41 although the out-of-pocket cost borne by patients varies considerably by insurance formulary and coverage.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Cost
What the sources say
- Not checked yetcites [27] American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43(suppl 1): S98– S110. doi: 10.2337/dc20-S009 31862752 source
- Not checked yetcites [41] Sumarsono A, Everett BM, McGuire DK, Trends in aggregate use and associated expenditures of antihyperglycemic therapies among US Medicare beneficiaries between 2012 and 2017. JAMA Intern Med. 2020; 180(1): 141– 144. doi: 10.1001/jamainternmed.2019.3884 PMC6777260 31566649 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Most recently approved for clinical use, oral semaglutide has a favorable safety profile and is currently undergoing regulatory evaluation and further study for cardiovascular outcomes.”
- Also stated in: § Observations · plain
“Cardiovascular safety was observed with oral semaglutide,12 which has been recently approved by the Food and Drug Administration as the first oral GLP-1RA option for type 2 diabetes; a dedicated randomized clinical trial to evaluate the cardiovascular outcomes associated with oral semaglutide use is currently being conducted.13”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > OBSERVATIONS
What the sources say
- Not checked yetcites [12] Husain M, Birkenfeld AL, Donsmark M,; PIONEER 6 Investigators. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019; 381(9): 841– 851. doi: 10.1056/NEJMoa1901118 31185157 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Observations · plain
In the paper
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Harmony Outcomes was the only trial that demonstrated prevention of HF events in at-risk patients with type 2 diabetes; albiglutide was associated with a statistically significant reduction in HF hospitalization (hazard ratio, 0.71; 95% CI, 0.53–0.94; P < .001).4,8”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
- Not checked yetcites [8] Hernandez AF, Green JB, Janmohamed S,; Harmony Outcomes committees and investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018; 392(10157): 1519– 1529. doi: 10.1016/S0140-6736(18)32261-X 30291013 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given the pharmacological properties of GLP-1RA that increase the heart rate (which may be detrimental in HF), the safety of its use in patients with HF with reduced EF remains uncertain.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: GLP-1RAs have pharmacological properties that increase heart rate.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although data are limited on the use of GLP-1RAs in end-stage kidney disease (estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2), liraglutide, dulaglutide, and injectable semaglutide may be used in advanced chronic kidney disease (CKD) at any eGFR level and without dose adjustment (Table 1), in contrast with most other noninsulin diabetes therapies.”
- Also stated in: § Secondary Benefits · hedged
“Liraglutide, dulaglutide, and semaglutide may be used in patients with advanced CKD at any level of eGFR without dose adjustment.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Secondary Benefits · hedged
None of the sources cited for this claim have been checked yet.
In the paper
“Given the association of increased amputation risk with canagliflozin use reported in the CANVAS (Canagliflozin Cardiovascular Assessment Study) R trial, severe peripheral artery disease and/or active diabetic foot ulcers may favor GLP-1RA therapy over an SGLT2 inhibitor (at least over canagliflozin).”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Contraindications and Cautions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Despite these findings, GLP-1RAs are underused in eligible patients, particularly by cardiologists.”
- Also stated in: § Observations · plain
“Despite these favorable data and endorsements across diabetes and cardiology society publications, uptake of GLP-1RAs in clinical practice has lagged.”
- Also stated in: § Observations · plain
“Although the first GLP-1RA (exenatide) was approved in 2005 for use in the US and cardiovascular superiority with liraglutide was reported in 2016, less than 8% of individuals with type 2 diabetes and ASCVD were given GLP-1RA prescriptions in 2 US-based observational studies.22,23”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > IMPORTANCE
What the sources say
- Not checked yetcites [22] Arnold SV, de Lemos JA, Rosenson RS,; GOULD Investigators. Use of guideline-recommended risk reduction strategies among patients with diabetes and atherosclerotic cardiovascular disease. Circulation. 2019; 140(7): 618– 620. doi: 10.1161/CIRCULATIONAHA.119.041730 31174429 source
- Not checked yetcites [23] Weng W, Tian Y, Kong SX, The prevalence of cardiovascular disease and antidiabetes treatment characteristics among a large type 2 diabetes population in the United States. Endocrinol Diabetes Metab. 2019; 2(3): e00076. doi: 10.1002/edm2.76 31294089 PMC6613222 source
- Not checked yetcites [24] Vaduganathan M, Patel RB, Singh A, Prescription of glucagon-like peptide-1 receptor agonists by cardiologists. J Am Coll Cardiol. 2019; 73 (12): 1596– 1598.doi: 10.1016/j.jacc.2019.01.029 30922481 PMC6764415 source
- Not checked yetcites [25] Dave CV, Schneeweiss S, Wexler DJ, Brill G, Patorno E. Trends in clinical characteristics and prescribing preferences for SGLT2 inhibitors and GLP-1 receptor agonists, 2013–2018. Diabetes Care. 2020; 43(4): 921– 924. doi: 10.2337/dc19-1943 32041899 PMC7519473 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Observations · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Professional society guidelines now recommend GLP-1RA therapy for cardiovascular risk mitigation in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors, independent of glucose control or background antihyperglycemic therapy (other diabetes medications being used).”
- Also stated in: § Candidates for GLP-1RA Therapy · hedged
“Current society guidelines advise cardiologists to consider adding a GLP-1RAto the regimen of all patients with type 2 diabetes and established ASCVD or high ASCVD risk, regardless of their baseline glycemic control or background antihyperglycemic therapy (other diabetes medications already being used).15,16,21,27”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > OBSERVATIONS
What the sources say
- Not checked yetcites [15] American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43(suppl1): S111– S134. doi: 10.2337/dc20-S010 31862753 source
- Not checked yetcites [16] Das SR, Everett BM, Birtcher KK, 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2018; 72(24): 3200– 3223. doi: 10.1016/j.jacc.2018.09.020 30497881 PMC7560953 source
- Not checked yetcites [21] Cosentino F, Grant PJ, Aboyans V,; ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255– 323. doi: 10.1093/eurheartj/ehz486 31497854 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Candidates for GLP-1RA Therapy · hedged
In the paper
“Complications of diabetic retinopathy were rare but more commonly seen in patients who received injectable semaglutide vs placebo (3.0% vs 1.8%) in SUSTAIN-6.7”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Contraindications and Cautions
What the sources say
- Not checked yetcites [7] Marso SP, Bain SC, Consoli A,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This findins has been attributed to the rapid reduction in blood glucose in a patient population at higher risk for retinopathy complications, which has been observed with insulin therapy when poorly controlled hyperglycemia is rapidly rectified.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Contraindications and Cautions
What the sources say
- Not checked yetcites [7] Marso SP, Bain SC, Consoli A,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A meta-analysis of large cardiovascular outcomes trials of patients with type 2 diabetes reported a nominally significant 9% reduction in heart failure (HF) hospitalization.4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“To date, randomized clinical trials of albiglutide, dulaglutide, liraglutide, and injectable semaglutide have reported favorable cardiovascular outcomes.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > OBSERVATIONS
What the sources say
- Not checked yetcites [6] Marso SP, Daniels GH, Brown-Frandsen K,; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375(4): 311– 322.doi: 10.1056/NEJMoa1603827 27295427 PMC4985288 source
- Not checked yetcites [7] Marso SP, Bain SC, Consoli A,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375(19): 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source
- Not checked yetcites [8] Hernandez AF, Green JB, Janmohamed S,; Harmony Outcomes committees and investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018; 392(10157): 1519– 1529. doi: 10.1016/S0140-6736(18)32261-X 30291013 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“High-dose oral semaglutide was also associated with considerable weight loss.30”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
What the sources say
- Not checked yetcites [30] Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA. 2017; 318(15): 1460– 1470. doi: 10.1001/jama.2017.14752 29049653 PMC5817971 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These agents are associated with similar or greater weight loss compared with that observed with SGLT2 inhibitors.29”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Secondary Benefits
What the sources say
- Not checked yetcites [29] Vilsbaøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012; 344: d7771. doi: 10.1136/bmj.d7771 22236411 PMC3256253 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In addition, postmarketing reports have suggested the possibility of pancreatitis associated with GLP-1RAs, although a risk signal has not been observed in prospective randomized clinical trials.4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The therapy may increase the risk of gallbladder disease, including cholelithiasis and cholecystitis45,46; suggestive symptoms (eg, fever, right upper-quadrant abdominal pain) should be reviewed with the patient.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
What the sources say
- Not checked yetcites [45] Faillie JL, Yu OH, Yin H, Hillaire-Buys D, Barkun A, Azoulay L. Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus. JAMA Intern Med. 2016; 176(10): 1474– 1481. doi: 10.1001/jamainternmed.2016.1531 27478902
- Not checked yetcites [46] Nauck MA, Muus Ghorbani ML, Kreiner E, Saevereid HA, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial. Diabetes Care. 2019; 42(10): 1912– 1920. doi: 10.2337/dc19-0415 31399438 PMC7364668
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Anticipatory guidance, with the expectation of early satiety and transient gastrointestinal upset soon after GLP-1RA initiation that typically improve within 4 weeks of continued use, is critical for promoting both short- and long-term patient adherence.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, GLP-1RAs have a favorable safety profile.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The most common adverse effect of this therapy is gastrointestinal upset, including nausea, vomiting, diarrhea, early satiety, decreased appetite, and abdominal bloating, with 15% to 40% of patients experiencing symptoms within the first 4 weeks of treatment.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As mentioned, cardiovascular advantages have been demonstrated in trials of liraglutide, dulaglutide, and injectable semaglutide, and thus these are currently the preferred GLP-1RAs in patients with established ASCVD or at high risk for developing ASCVD.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, postmarketing reports have suggested the possibility of pancreatitis associated with GLP-1RAs, although a risk signal has not been observed in prospective randomized clinical trials.4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Injection-site reactions, including erythema, rash, and subcutaneous nodules, are commonly observed with extended-release exenatide vs other GLP-1Ras and may be prevented by rotating the injection sites.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Robust clinical benefits, including decreased mortality, were observed with dapagliflozin in the DAPA-HF (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) trial, regardless of type 2 diabetes status.44”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Secondary Benefits
What the sources say
- Not checked yetcites [44] McMurray JJV, Solomon SD, Inzucchi SE,; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. NEnglJ Med. 2019; 381 (21): 1995– 2008. doi: 10.1056/NEJMoa1911303 31535829
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Specifically, hypoglycemia is rare except when GLP-1RAs are coadministered with sulfonylureas or insulin.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, gastrointestinal symptoms are typically transient, mild, and mitigated by starting with a low dose and up-titrating as tolerated (Table 1).”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 11
- Probably not a substantial claim. 1
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Furthermore, 2 small randomized clinical trials of liraglutide in patients with HF with reduced EF, 1 of which enrolled patients with recent HF hospitalization, suggested potential harm of liraglutide, although neither trial found statistically significant differences.36,37”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
What the sources say
- Supportedcites [36] Margulies KB, Hernandez AF, Redfield MM,; NHLBI Heart Failure Clinical Research Network. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016; 316(5): 500– 508. doi: 10.1001/jama.2016.10260 27483064 PMC5021525 source
The Design section identifies this as a randomized trial in patients with reduced LVEF who were recently hospitalized. The Discussion describes nonsignificant signals of harm and recommends caution; the Results report no statistically significant differences in deaths or heart-failure rehospitalizations. This supports the claim as it applies to this trial, rather than establishing the findings of the other cited trial. (LLM, conf=0.92)
- Disputedcites [37] Jorsal A, Kistorp C, Holmager P, Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)— a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017; 19(1): 69– 77. doi: 10.1002/ejhf.657 27790809 sourceExperimental — accuracy not yet measured
The LIVE trial supports the suggestion of potential harm, but contradicts the claim that neither trial found a statistically significant difference. Its Results (p. 5) report significantly more serious cardiac adverse events with liraglutide than placebo (10% versus 3%; P = 0.04). The cited paper cannot establish the finding of the other trial. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
In the paper
“In addition to standard of care and largely independent of hyperglycemic outcomes, the use of GLP-1RAs has demonstrated mean relative risk reduction in MACE by 12%, cardiovascular death by 12%, all-cause mortality by 12%, stroke by 16%, myocardial infarction by 9%, and composite kidney events by 17% (driven by improvements in albuminuria).4”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Observations
What the sources say
- Not checked yetcites [4] Kristensen SL, Rorth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Participants with prevalent HF experienced consistent reduction in MACE and cardiovascular and all-cause death with liraglutide compared with participants in the non-HF subgroup and showed no excess risk of HF hospitalization.32”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Candidates for GLP-1RA Therapy > Special Considerations
What the sources say
- Not checked yetcites [32] Marso SP, Baeres FMM, Bain SC,; LEADER Trial Investigators. Effects of liraglutide on cardiovascular outcomes in patients with diabetes with or without heart failure. JAm Coll Cardiol. 2020; 75(10): 1128– 1141. doi: 10.1016/j.jacc.2019.12.063 32164886 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In general, GLP-1RAs are contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (Box), although these concerns are based exclusively on observations in rodent models with uncertain human clinical relevance, as reflected in US product labeling.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Contraindications and Cautions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We searched PubMed for English-language studies published between January 1, 2005, and October 31, 2019. This search identified 7 cardiovascular outcomes trials of GLP-1RA therapy.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Abstract > CONCLUSIONS AND RELEVANCE
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Specifically, GLP-1RAs are predominantly associated with decreased atherosclerosis-mediated events, whereas SGLT2 inhibitors are predominantly associated with HF and CKD outcomes.38”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both
What the sources say
- Not checked yetcites [38] Garg V, Verma S, Connelly K. Mechanistic insights regarding the role of SGLT2 inhibitors and GLP1 agonist drugs on cardiovascular disease in diabetes. Prog Cardiovasc Dis. 2019; 62(4): 349– 357. doi: 10.1016/j.pcad.2019.07.005 31381891 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, increased amputation risk has not been seen with other SGLT2 inhibitors, nor with canagliflozin in the subsequent CREDENCE (Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluation) trial, in which such adverse events were systematically collected.40”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Contraindications and Cautions
What the sources say
- Not checked yetcites [40] PerkovicV Jardine MJ, Neal B,; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019; 380(24): 2295– 2306. doi: 10.1056/NEJMoa1811744 30990260 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“When both medication classes are unaffordable, metformin is a less costly, widely available alternative that has been associated with favorable cardiometabolic outcomes.42”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Cost
What the sources say
- Not checked yetcites [42] Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control intype2 diabetes. N Engl J Med. 2008; 359 (15): 1577– 1589. doi: 10.1056/NEJMoa0806470 18784090 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Society recommendations and guidelines support the concurrent use of GLP-1RAs and SGLT2 inhibitors when needed for adequate glycemic control, but data on whether such combinations may yield incremental cardiovascular advantages are lackingthusfar.15,16,21”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Concurrent Use of GLP-1RAs and SGLT2 Inhibitors
What the sources say
- Not checked yetcites [15] American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43(suppl1): S111– S134. doi: 10.2337/dc20-S010 31862753 source
- Not checked yetcites [16] Das SR, Everett BM, Birtcher KK, 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2018; 72(24): 3200– 3223. doi: 10.1016/j.jacc.2018.09.020 30497881 PMC7560953 source
- Not checked yetcites [21] Cosentino F, Grant PJ, Aboyans V,; ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255– 323. doi: 10.1093/eurheartj/ehz486 31497854 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Dipeptidyl peptidase 4 inhibitors should be discontinued before initiating GLP-1RA therapy, given the lack of anticipated additive efficacy owing to overlapping mechanisms of action.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Adjusting Other Antihyperglycemic Medications
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As discussed, GLP-1RA initiation in individuals with poor baseline glycemic control may be a factor in worsening of diabetic retinopathy.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > GLP-1RAs, SGLT2 Inhibitors, or Both > Selecting a GLP-1RA and Patient Counseling
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“GLP-1RAs appear to be a safe, well-tolerated therapy that can improve cardiovascular outcomes, largely independent of their antihyperglycemic properties.”
§ Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The most common adverse effect of GLP-1RA therapy is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated.
“Its most common adverse effect is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated.”
The paper relies on this without support.
Without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia.
“Depending on baseline glycemic control, sulfonylureas and insulin may need to be decreased before GLP-1RA initiation; without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia.”
The paper relies on this without support.
GLP-1RAs delay gastric emptying.
“Because GLP-1RAs delay gastric emptying, caution should be used in prescribing these agents to patients with gastroparesis, chronic nausea, or previous gastric surgical procedure.”
The paper relies on this without support.
GLP-1RAs have pharmacological properties that increase heart rate.
“Given the pharmacological properties of GLP-1RA that increase the heart rate (which may be detrimental in HF), the safety of its use in patients with HF with reduced EF remains uncertain.”
The paper relies on this without support.
SGLT2 inhibitors are associated with increased risk for genital mycotic infections.
“Because SGLT2 inhibitors are associated with increased risk for genital mycotic infections, a history of recurrent genital mycotic infections may additionally favor GLP-1RA over SGLT2 inhibitors.”
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?
In the citing paper
“In addition, commercially available GLP-1 receptor agonists have demonstrated improvements in major adverse cardiovascular events in patients with T2D.18”
Citations
Cites
10-year follow-up of intensive glucose control in type 2 diabetes
Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R., & Neil, H. A. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0806470 · Cited by 7,751
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
McMurray, J. J. V., Solomon, S. D., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Anand, I. S., Bělohlávek, J., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1911303 · Cited by 7,140
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607141 · Cited by 6,900
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811744 · Cited by 6,189
Cosentino, F., Grant, P. J., Aboyans, V., Bailey, C. J., Ceriello, A., Delgado, V., Federici, M., Filippatos, G., Grobbee, D. E., Hansen, T. B., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz486 · Cited by 4,763
Arnett, D. K., Blumenthal, R. S., Albert, M. A., Buroker, A. B., Goldberger, Z. D., Hahn, E. J., Himmelfarb, C. D., Khera, A., Lloyd-Jones, D., McEvoy, J. W., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000678 · Cited by 4,536
(2019) · doi:10.1161/cir.0000000000000677 · Cited by 4,501
Gerstein, 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
Zelniker, T. A., Wiviott, S. D., Raz, I., Im, K., Goodrich, E. L., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Furtado, R. H. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32590-x · Cited by 2,845
Self-citation
Cited by
Sorted by citations
Joseph, J. J., Deedwania, P., Acharya, T., Aguilar, D., Bhatt, D. L., Chyun, D. A., Di Palo, K. E., Golden, S. H., Sperling, L. S., & on behalf of the American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, T. A. V. B. C. O. C. C. A. C. O. H. (2022) · Circulation · doi:10.1161/cir.0000000000001040 · Cited by 660
Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications
Alharbi, S. H. (2024) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188231222367 · Cited by 358
Gorgojo-Martínez, J. J., Mezquita-Raya, P., Carretero-Gómez, J., Castro, A., Cebrián-Cuenca, A., de Torres-Sánchez, A., García-de-Lucas, M. D., Núñez, J., Obaya, J. C., Soler, M. J., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm12010145 · Cited by 358
The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease
Du, H., Meng, X., Yao, Y., & Xu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1033479 · Cited by 125
Ma, Y., Kong, C., Guo, Z., Wang, M., Wang, P., Liu, F., Yang, D., Zheng, Y., & Tang, Q. (2024) · Nature Communications · doi:10.1038/s41467-024-48970-2 · Cited by 105
Metadata
- Authors
- Honigberg, M. C., Chang, L.-S., McGuire, D. K., Plutzky, J., Aroda, V. R., & Vaduganathan, M.
- Affiliations
- Massachusetts General Hospital (US)
- Brigham and Women's Hospital (US)
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2020-10-01
- Volume
- 5
- Issue
- 10
- Pages
- 1182
- ISSN
- 2380-6583 (ISSN-L)
- PMC
- PMC7744318
- OpenAlex
- W3036179581
- Cited by
- 127
- References
- 47
- Citations by year
- 2026: 20 · 2025: 24 · 2024: 29 · 2023: 18 · 2022: 18 · 2021: 16 · 2020: 2
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL094301)
- 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 › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- GLP-1 receptor agonists, type 2 diabetes, atherosclerotic cardiovascular disease, cardiovascular risk reduction, semaglutide, albiglutide, dulaglutide, liraglutide, obesity, chronic kidney disease, gastrointestinal adverse effects, hypoglycemia, sulfonylureas, insulin, multidisciplinary care, shared decision-making
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Contraindications, Drug, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Heart Failure, Humans, Hypoglycemic Agents, Obesity, Overweight, Renal Insufficiency, Chronic
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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