Incretin-based therapies in 2021 – Current status and perspectives for the future

Rizzo, Manfredi; Nauck, Michael A.; Mantzoros, Christos S.

doi:10.1016/j.metabol.2021.154843

Cited by 23 publications

(14 citation statements)

References 33 publications

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“…There is increasing interest in the effects of novel antidiabetic treatments on atherogenic lipoproteins since such therapies significantly impact the cardiovascular outcome in patients with type-2 diabetes; sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown over the last few years to reduce cardiovascular events and mortality, while dipeptidyl peptidase-4 inhibitors (DPP-4i) have a neutral effect with cardiovascular safety, although with no benefit [64,65]. The mechanisms involved in such divergent cardiovascular effects are still largely unclear, and it has been postulated that this may be linked to a direct anti-atherosclerotic action possessed by some of these novel agents [66,67].…”

Section: The Role Of Innovative Antidiabetic Therapies On Atherogenic Lipoproteinsmentioning

confidence: 99%

A New Look at Novel Cardiovascular Risk Biomarkers: The Role of Atherogenic Lipoproteins and Innovative Antidiabetic Therapies

et al. 2022

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The presence of residual cardiovascular disease (CVD) risk is a current dilemma in clinical practice; indeed, despite optimal management and treatment, a considerable proportion of patients still undergo major CV events. Novel lipoprotein biomarkers are suggested as possible targets for improving the outcomes of patients at higher risk for CVD, and their impact on major CV events and mortality have previously been investigated. Innovative antidiabetic therapies have recently shown a significant reduction in atherogenic lipoproteins, beyond their effects on glucose parameters; it has also been suggested that such anti-atherogenic effect may represent a valuable mechanistic explanation for the cardiovascular benefit of, at least, some of the novel antidiabetic agents, such as glucagon-like peptide-1 receptor agonists. This emphasizes the need for further research in the field in order to clearly assess the effects of innovative treatments on different novel biomarkers, including atherogenic lipoproteins, such as small dense low-density lipoprotein (LDL), lipoprotein(a) (Lp(a)) and dysfunctional high-density lipoprotein (HDL). The current article discusses the clinical importance of novel lipid biomarkers for better management of patients in order to overcome residual cardiovascular risk.

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Section: The Role Of Innovative Antidiabetic Therapies On Atherogenic Lipoproteinsmentioning

confidence: 99%

A New Look at Novel Cardiovascular Risk Biomarkers: The Role of Atherogenic Lipoproteins and Innovative Antidiabetic Therapies

et al. 2022

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“…The use of these molecules in association with GLP1-RAs has also been recommended for patients at high cardiovascular risk in association with conventional therapies precisely for the improvement of various cardiovascular risk factors, although the adoption of these novel anti-diabetic treatments remains suboptimal in most countries [ 20 ]. GLP-1 agonists exert a very important pleiotropic effect in improving cardiovascular health [ 21 , 22 ] and some of them, such as liraglutide, are able to improve subclinical atherosclerosis by reducing atherogenic small dense low-density lipoproteins (LDL) [ 23 ]. This important molecular effect has been proposed as a key mechanism by which GLP-1 agonists are able to have a positive cardiovascular outcome [ 24 ]; indeed, the oxidation in the intima of small dense LDL is considered the first intra-vessel alteration of the complex atherosclerotic cascade, leading to the formation of foam cells and, ultimately, of atherosclerotic plaque [ 25 ].…”

Section: Current Approaches In the Management Of T2dmmentioning

confidence: 99%

An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes

et al. 2022

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Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists (“glitazones”) are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies.

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“…Among these novel treatments, glucagon-like peptide-1 receptor agonists (GLP-1RAs) mimic the effects of human native GLP-1 that, produced in enteroendocrine cells and secreted after meal ingestion, regulate glycemia through glucagon inhibition and stimulation of insulin secretion by pancreatic beta cells in a glucose-dependent manner [160]. In diabetic subjects, the incretin effect is reduced or absent; GLP1-RAs are able to restore this balance and are therefore widely used for the treatment of T2DM due to their ability to lower glucose and cardiometabolic risk, with a low risk of hypoglycemia [161]. The most frequent side effects are nausea and other minor gastrointestinal symptoms, which are usually transient and mild in intensity, mainly occurring in the dose-escalation phase of the treatment [162].…”

Section: Novel Antidiabetic Glucagon-like Peptide-1 Receptor Agonists (Glp-1ras) Therapies and Colorectal Cancermentioning

confidence: 99%

Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

Vekić

Stefanović

Giglio

et al. 2021

IJMS

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Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.

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Incretin-based therapies in 2021 – Current status and perspectives for the future

Cited by 23 publications

References 33 publications

A New Look at Novel Cardiovascular Risk Biomarkers: The Role of Atherogenic Lipoproteins and Innovative Antidiabetic Therapies

A New Look at Novel Cardiovascular Risk Biomarkers: The Role of Atherogenic Lipoproteins and Innovative Antidiabetic Therapies

An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes

Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

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