Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the <scp>LEADER</scp> and <scp>SUSTAIN</scp> 6 clinical trials

Verma, Subodh; Bain, Stephen C.; Honoré, Julie Broe; Mann, Johannes F.E.; Nauck, Michael A.; Pratley, Richard E.; Rasmussen, Søren; Ripa, Maria Sejersten; Zinman, Bernard; Buse, John B.

doi:10.1111/dom.14140

Cited by 11 publications

(8 citation statements)

References 15 publications

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“…27 In a post hoc analysis of both the LEADER and SUSTAIN 6 trials, patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) had increased risk for 3-point MACE compared with patients without complications. 42 However, the beneficial effects of liraglutide and semaglutide effects were similar in patients with or without microvascular complications, except for neuropathy in SUSTAIN 6. 4 In the EXSCEL trial, there were fewer cardiovascular events in patients that were treated with OW exenatide than with placebo; however, the difference did not reach statistical significance (P ¼ 0.06).…”

Section: Fig 4)mentioning

confidence: 92%

Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes

Mosenzon¹,

Schechter²,

Leibowitz

2021

Advances in Chronic Kidney Disease

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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective in reducing glycemia in patients with type 2 diabetes (T2D). These medications effectively reduce cardiovascular (CV) risk in patients with T2D and established CV disease or with multiple risk factors. In addition, treatment with GLP-1 RA may exert protective effects on the diabetic kidney. Herein, we summarize the findings regarding the kidney safety and efficacy of GLP-1 RAs in patients with T2D. We review data from GLP-1 RAs phase 3 kidney studies, CV outcome trials, as well as real-world evidence. The accumulating data show that treatment with GLP-1 RAs is safe, well-tolerated, and effective in patients with different levels of kidney dysfunction. Furthermore, CV outcome trials suggest that GLP-1 RAs reduce albuminuria and may attenuate the decline in kidney function over time. The ongoing FLOW trial studying the effects of semaglutide in patients with diabetic kidney disease is expected to shed light on the effects of GLP-1 RAs on kidney outcomes and clarify their role in the management of patients with T2D and kidney disease.

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Section: Fig 4)mentioning

confidence: 92%

Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes

Mosenzon¹,

Schechter²,

Leibowitz

2021

Advances in Chronic Kidney Disease

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“… 51 Data from the CVOTs also support the role of microvascular disease, with further analysis of the LEADER trial showing that the risk reduction with liraglutide for the composite CV outcome of CV death, nonfatal MI, or nonfatal stroke was greater in patients with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m 2 versus 60 mL/min/1.73 m 2 or greater, 52 although this could be secondary to hypertension or other renal anomalies. Similarly, a post hoc analysis of the LEADER and SUSTAIN‐6 studies showed that microvascular disease was associated with increased risk of MACE, 53 and analysis of the EMPA‐REG OUTCOME study showed that the presence of microvascular disease at baseline was associated with a higher risk of HHF and CVD death (but not three‐point MACE), with a trend for worsening HF as the number of microvascular complications increased, 54 similar to that reported by Brownrigg et al 55 (Figure 2 ). Diabetic cardiomyopathy 56 is also associated with the presence of microvascular complications 57 and is proposed to be caused by microangiopathy.…”

Section: The Presence Of Microvascular Disease Predicts Cvd...mentioning

confidence: 98%

Reconsidering the role of glycaemic control in cardiovascular disease risk in type 2 diabetes: A 21st century assessment

Aroda

Eckel

2022

Diabetes Obesity Metabolism

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It is well known that the multiple factors contributing to the pathogenesis of type 2 diabetes (T2D) confer an increased risk of developing cardiovascular disease (CVD).Although the relationship between hyperglycaemia and increased microvascular risk is well established, the relative contribution of hyperglycaemia to macrovascular events has been strongly debated, particularly owing to the failure of attempts to reduce CVD risk through normalizing glycaemia with traditional therapies in high-risk populations. The debate has been further fuelled by the relatively recent discovery of the cardioprotective properties of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Further, as guidelines now recommend individualizing glycaemic targets, highlighting the importance of achieving glycated haemoglobin (HbA1c) goals safely, the previously observed negative influences of intensive therapy on CVD risk might not present if trials were repeated using current-day treatments and individualized HbA1c goals. Emerging longitudinal data illuminate the overall effect of excess glucose, the impacts of magnitude and duration of hyperglycaemia on disease progression and risk of CVD complications, and the importance of glycaemic control at or early after diagnosis of T2D for prevention of complications. Herein, we review the role of glucose as a modifiable cardiovascular (CV) risk factor, the role of microvascular disease in predicting macrovascular risk, and the deleterious impact of therapeutic inertia on CVD risk. We reconcile new and old data to offer a current perspective, highlighting the importance of effective, early treatment in reducing latent CV risk, and the timely use of appropriate therapy individualized to each patient's needs.

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“…Although the incidence of microvascular complications is decreasing [ 31 ], they increase the risk of major adverse cardiovascular events (MACE) and multiple organ complications [ 32 ]. Studies on the effects of liraglutide on microvascular outcomes include microvascular complications, such as nephropathy [ 33 , 34 ], retinopathy [ 34 ], or neuropathy [ 33 ], as well as effects on coronary microvascular function [ 35 , 36 ].…”

Section: Microvascular Outcomes Of Liraglutide Treatmentmentioning

confidence: 99%

New Insights into the Use of Liraglutide—Impact on Cardiovascular Risk and Microvascular Outcomes

et al. 2023

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Despite the availability of many glucose-lowering drugs, patients with type 2 diabetes mellitus (T2DM) often do not achieve the desired effect, and cardiovascular complications remain the leading cause of death in this group of patients. Recently, more and more attention has been paid to the properties of drugs, with particular emphasis on the possibility of reducing cardiovascular risk. One of them is liraglutide, which belongs to long-acting analogs of glucagon-like peptides-1 (GLP-1); it imitates incretins and causes an increase in insulin secretion. The current study focused on analyzing the efficacy and safety of liraglutide, as well as its impact on microvascular and cardiovascular outcomes in the treatment of patients with T2DM. Hyperglycemia-induced endothelial dysfunction, which is known to play a key role in maintaining cardiovascular homeostasis, is common in diabetes. Liraglutide reduces endothelial dysfunction by reversing damage to endothelial cells. By reducing the generation of reactive oxygen species (ROS), thereby affecting Bax, Bcl-2 protein levels, and restoring signaling pathways, Liraglutide reduces oxidative stress, inflammation, and prevents endothelial cell apoptosis. Liraglutide has beneficial effects on the cardiovascular system; patients with high cardiovascular risk particularly benefit from treatment, as it reduces their major adverse cardiovascular event (MACE) rate, which takes into account cardiovascular death, stroke, and non-fatal myocardial infarction. Liraglutide reduces the occurrence and progression of nephropathy, which is one of the most common microvascular complications of diabetes.

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Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the LEADER and SUSTAIN 6 clinical trials

Cited by 11 publications

References 15 publications

Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes

Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes

Reconsidering the role of glycaemic control in cardiovascular disease risk in type 2 diabetes: A 21st century assessment

New Insights into the Use of Liraglutide—Impact on Cardiovascular Risk and Microvascular Outcomes

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