Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the <scp>FIGHT</scp> trial

Sharma, Abhinav; Ambrosy, Andrew P.; DeVore, Adam D.; Margulies, Kenneth B.; McNulty, Steven E.; Mentz, Robert J.; Hernandez, Adrian F.; Felker, G. Michael; Cooper, Lauren B.; Lala, Anuradha; Vader, Justin; Groake, John D.; Borlaug, Barry A.; Velázquez, Eric J.

doi:10.1002/ehf2.12334

Cited by 29 publications

(19 citation statements)

References 28 publications

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“…At baseline, the median trial mean glycated haemoglobin A1c was 8.1% and BMI was 30.1. Eligibility criteria included coronary artery disease or macrovascular disease in 35 trials, 3 6 7 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 atrial fibrillation in 1 trial, 65 heart failure in 9 trials, 66 67 68 69 70 71 72 73 74 chronic kidney disease and/or albuminuria in 37 trials, 8 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 …”

Section: Resultsmentioning

confidence: 99%

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Palmer

Tendal

Mustafa

et al. 2021

BMJ

416

310

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Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool ( https://magicevidence.org/match-it/200820dist/#!/ ) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.

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Section: Resultsmentioning

confidence: 99%

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Palmer

Tendal

Mustafa

et al. 2021

BMJ

416

310

View full text Add to dashboard Cite

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“…With regard to effects on HF, the CVOTs did not find that GLP‐1RAs reduced hospitalizations for HF (Table ), even though early small studies on exenatide showed HF benefits in the immediate post‐MI period. With liraglutide, in some small studies, there appeared to be worse outcomes in patients with T2DM who had severe congestive heart failure; however in the large LEADER study there was no adverse effect on HF outcomes …”

Section: Ascvd Vs Hf Benefits In the Cvotsmentioning

confidence: 99%

“…With liraglutide, in some small studies, there appeared to be worse outcomes in patients with T2DM who had severe congestive heart failure; however in the large LEADER study there was no adverse effect on HF outcomes. 30,36,37…”

Section: Dpp-4 Inhibitor Cvotsmentioning

confidence: 99%

Navigating the “MACE” in Cardiovascular Outcomes Trials and decoding the relevance of Atherosclerotic Cardiovascular Disease benefits versus Heart Failure benefits

Hupfeld

Mudaliar

2019

Diabetes Obesity Metabolism

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The publication of results from recent cardiovascular outcome trials (CVOTs) has transformed the landscape of diabetes treatment. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose co-transporter-2 (SGLT2) inhibitors have demonstrated CV benefits in large, well-conducted, randomized studies. Today, empagliflozin, canagliflozin and liraglutide are US Food and Drug Administrationapproved not only for glucose-lowering, but also to reduce the risk of cardiovascular (CV) events/CV mortality in people with type 2 diabetes (T2DM) and established CV disease (CVD)/high CVD risk. Although the CVOTs were primarily powered for CV safety (non-inferiority), they also demonstrated CV efficacy (superiority). This initially surprised many in the diabetes community, but the replication of the CV benefits with different compounds in the same class alleviated concerns about the CV benefits being chance findings. However, many questions remain. While the heterogeneity in the CV benefits in the various CVOTs can be attributed to the variability in CV risk in the different studies, the reason(s) for the differences in the CV benefits between the GLP-1RA class and the SGLT2 inhibitor class appear to be more com-plex. An analysis of major adverse cardiovascular events (MACE) in the CVOTs shows that the CV benefits of GLP-1RAs are predominantly specific to atherosclerotic CV events (non-fatal myocardial infarction [MI], non-fatal stroke and CV death). By contrast, the SGLT2 inhibitors do not have any significant effects on atherosclerotic CV events (non-fatal MI/stroke). Their benefits are predominantly on hospitalization for heart failure (HF), suggesting effects primarily on myocardial function ("the pump"), and not on the "pipes" (coronary arteries). In the present review, we discuss the rationale for the conduct of CVOTs, highlight the inability of the classic three-point MACE to capture the entire spectrum of atherosclerotic and non-atherosclerotic CVD morbidity, especially HF in T2DM, and discuss the results of the CVOTs with a focus on the clinical significance of atherosclerotic CVD (ASCVD) versus HF, which develops in a sizeable proportion of people with diabetes and without prior ASCVD.

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“…The preliminary results of FIGHT trial, that evaluates weight reduction benefit in patients with heart failure, showed that liraglutide was associated with a significant weight reduction and decreased triglyceride levels. However, the cardioprotective effects on patients with reduced left ventricular ejection fraction were not significant (32,33).…”

Section: Evidence Of Glp-1 Agonists On Metabolismmentioning

confidence: 99%

Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)

et al. 2020

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Patients with type 2 diabetes exhibit higher cardiovascular risk than normal individuals. Optimal blood glucose levels are rarely achieved in diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a new antidiabetic drug class with multiple metabolic effects. Some trials have evaluated their safety, but it has been recently demonstrated that this new class has cardiovascular benefits, through other mechanisms than glycemic control. The use of GLP-1RAs was associated with a significant reduction of cardiovascular and all-cause mortality, with a safe profile related to pancreatitis or thyroid cancer, as compared with placebo. This review presents the cardiovascular and metabolic benefits of GLP-1 RAs versus placebo, in patients with type 2 diabetes. Semaglutide and liraglutide demonstrated a reduction in cardiovascular events, with similar rates on cardiovascular mortality. Ongoing trials assess the cardiovascular benefits and side effects of dulaglutide treatment. Exenatide and liraglutide demonstrated the decrease of blood pressure values, weight reduction and improvement of dyslipidemia. Liraglutide induced, both in vivo and in vitro, an improvement of blood circulation, increasing the nitric oxide level and inhibiting the adhesion and procoagulant factors. Also, liraglutide demonstrated beneficial effects on cardiac remodeling after myocardial infarction, but more large trials are required. However, the international guidelines recommend using GLP-1 RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line agents in patients intolerant to metformin. Contents 1. Introduction 2. Mechanism of action of GLP-1 hormone and its pleiotropic effects 3. Evidence of cardiovascular effects of GLP-1 agonists 4. Evidence of GLP-1 agonists on metabolism 5. Conclusions

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Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial

Abstract: Liraglutide is an efficacious weight loss agent in patients with HFrEF. These findings will require further exploration in a well-powered cardiovascular outcomes trial.

Cited by 29 publications

References 28 publications

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Navigating the “MACE” in Cardiovascular Outcomes Trials and decoding the relevance of Atherosclerotic Cardiovascular Disease benefits versus Heart Failure benefits

Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)

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