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Oral Semaglutide: First-in-Class Oral GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus.
Cowart, K
The Annals of pharmacotherapy. 2020;(5):478-485
Abstract
Objective:The purpose of this article is to review the pharmacological characteristics and clinical evidence of oral semaglutide for the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A MEDLINE/PubMed search was conducted between January 1, 2005, and September 30, 2019. Search terms included semaglutide, glucagon-like peptide 1 receptor agonist, GLP-1 receptor agonist, and type 2 diabetes. Study Selection and Data Extraction Quantification: The following study designs were included in the analysis: systematic review and/or meta-analyses, clinical trial, or observational study design. Narrative reviews were excluded. Articles were included only if they were published in the English language or evaluated oral semaglutide with regard to pharmacology, pharmacokinetics, safety, and efficacy in humans. Data Synthesis: Oral semaglutide has been Food and Drug Administration approved for the treatment of T2DM as an adjunct to diet and exercise. Oral semaglutide has been shown to result in an absolute hemoglobin A1C reduction between -0.5% and -1.5% and weight reductions between -1 and -4.7 kg. Oral semaglutide has been shown to be noninferior to placebo for cardiovascular (CV) safety although additional CV outcomes trials are ongoing. Adverse effects appear to be similar to those of other glucagon-like peptide-1 receptor agonists and are gastrointestinal in nature. Relevance to Patient Care and Clinical Practice: Oral semaglutide may be appropriate as second- or third-line add-on therapy for patients with T2DM who are not meeting treatment goals on metformin and are overweight and reluctant to use an injectable drug. Conclusions: Oral semaglutide appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2DM.
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2.
Impact of glucagon-like peptide 1 receptor agonists and sodium-glucose transport protein 2 inhibitors on blood pressure and lipid profile.
Muzurović, E, Mikhailidis, DP
Expert opinion on pharmacotherapy. 2020;(17):2125-2135
Abstract
INTRODUCTION Type 2 diabetes mellitus (T2DM) is associated with increased prevalence of cardiovascular (CV) disease (CVD). Optimal anti-hyperglycemic agents should include control of multiple CV risk factors (RF) to improve macrovascular and microvascular complications, as well as glycemia. AREAS COVERED In this narrative review, the authors focus on the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) on blood pressure (BP) and the lipid profile, two well-established CV RF. EXPERT OPINION Results from recent CV outcome trials (CVOTs), showed the impact of GLP-1 RA and SGLT2i on BP and lipid levels. These classes of medication can alter cardiac function by affecting the process of atherosclerosis and/or hemodynamic status. The results of published GLP1-RA and SGLT2i CVOTs have shown multifactorial benefits; in addition to the main effects on glycemia and body weight (BW), there are also positive but moderate effects on BP and lipid levels. Full advantage of the pleiotropic benefit of these agents should be taken to prevent CV events.
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3.
Series: Implications of the recent CVOTs in type 2 diabetes: Impact on guidelines: The endocrinologist point of view.
Scheen, AJ
Diabetes research and clinical practice. 2020;:107726
Abstract
The management of type 2 diabetes mellitus (T2DM) essentially consists in controlling hyperglycaemia, together with other vascular risk factors, in order to reduce the incidence and severity of diabetic complications. Whereas glucose control using classical glucose-lowering agents (except perhaps metformin) largely fails to reduce cardiovascular disease (CVD), two new pharmacological classes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is), have proven their ability to reduce major cardiovascular events in patients with established CVD. Furthermore, SGLT2is reduced the risk of hospitalisation for heart failure and the progression of renal disease. According to the 2018 ADA-EASD consensus report, the choice of a second agent to be added to metformin should now be driven by the presence or not of atherosclerotic CVD, heart failure or renal disease, all conditions that should promote the use of a SGLT2i or a GLP-1 RA with proven efficacy. Thus endocrinologists have to face a new paradigm in the management of T2DM, with a shift from a primary objective of glucose control without inducing hypoglycaemia and weight gain to a goal of cardiovascular and renal protection, largely independent of glucose control. Of note, however, the latter remains crucial to reduce the risk of microangiopathy.
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4.
Compelling evidence for SGLT2 inhibitors and GLP-1 receptor agonists as first-line therapy in patients with diabetes at very high/high cardiovascular risk.
Marx, N, Grant, PJ, Cosentino, F
European heart journal. 2020;(2):329-330
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5.
Type 2 diabetes mellitus management in patients with chronic kidney disease: an update.
Kleinaki, Z, Kapnisi, S, Theodorelou-Charitou, SA, Nikas, IP, Paschou, SA
Hormones (Athens, Greece). 2020;(4):467-476
Abstract
Diabetes mellitus (DM) is a chronic multisystem disease. Diabetic nephropathy (DN) is one of its significant microvascular complications, associated with increased morbidity and mortality. The aim of this article is to review the literature regarding the latest advances in the management of type 2 DM (T2DM) in patients with chronic kidney disease (CKD). We initially refer to the screening guidelines, the diagnostic tests used, the need for novel biomarkers in DN, the recent advances in high-risk patient identification, the recommended glycemic targets, and concerns regarding the accuracy of HbA1c in these patients. Then, a detailed explanation of the appropriate medical management based on evidence from recent trials is presented, analyzed, and discussed. All patients with T2DM should be screened for albuminuria at initial diagnosis and annually thereafter. Proteomics and metabolomics today represent promising diagnostic tools. Optimal glycemic control, with individualized HbA1c targets, is fundamental for reduced onset or delayed progression of DN and microvascular complications, in general. This can be enhanced by lifestyle modifications and pharmacological interventions when needed. Metformin represents the first pharmacological step, with, recently, a broadened indication for patients with impaired renal function. If HbA1c remains above the target in patients with established CKD, SGLT2i or GLP-1 RA are the preferred second-line agents, as introduced in all new guidelines. This change was the result of recent landmark trials that highlighted the superiority of the two aforementioned medication categories in terms of both renal and cardiovascular outcomes.
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Infectious complications of newer agents in the fight against diabetes.
Stover, KR, Hugh, E, Sherman, JJ, Malinowski, SS, Berdahl, GJ, Riche, DM
The Nurse practitioner. 2020;(11):17-24
Abstract
Infectious complications have been reported with antidiabetic medications. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors have been associated with upper respiratory tract infections and urinary tract infections. Sodium-glucose cotransporter 2 inhibitors have been associated with lower limb amputations, urinary tract infections, genital mycotic infections, and Fournier gangrene.
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7.
Advances in the management of diabetes: therapies for type 2 diabetes.
Tsoutsouki, J, Wunna, W, Chowdhury, A, Chowdhury, TA
Postgraduate medical journal. 2020;(1140):610-618
Abstract
The incidence of type 2 diabetes is rapidly rising worldwide leading to an increasing burden of cardiovascular and microvascular complications. The aim of treatment of the condition is to improve quality of life and reduce such complications. To this end, improvement in glucose control remains an important consideration. In recent years, important therapeutic advances have occurred in the management of hyperglycaemia in people with type 2 diabetes. These include the use of dipeptidylpeptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors. The latter two classes appear to have some specific beneficial effects on cardiovascular and renal outcomes, independent of their antihyperglycaemic effects. This review aims to outline the current state of diagnosis and management of diabetes for the general physician, with a particular focus on new therapeutic agents for management of glucose in patients with type 2 diabetes.
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8.
Mechanisms by Which Glucagon-Like-Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors Reduce Cardiovascular Risk in Adults With Type 2 Diabetes Mellitus.
Sharma, A, Verma, S
Canadian journal of diabetes. 2020;(1):93-102
Abstract
The growing global burden of type 2 diabetes mellitus confers significant morbidity and mortality in addition to significant cost to local health-care systems. In recent years, 2 classes of therapies have shown some promise in reducing the risk of adverse cardiovascular (CV) events: 1) glucagon-like-peptide-1 (GLP-1) receptor agonists and 2) sodium-glucose cotransporter-2 (SGLT-2) inhibitors. The mechanisms whereby these therapies reduce the risk of adverse CV outcomes are emerging. Both classes of therapies have overlapping yet distinct mechanisms of action. GLP-1 receptor agonists appear to target the incretin axis, inhibit gastric mobility pathways, modify CV risk factors through weight reduction, induce protection of ischemia/reperfusion injury and improve endothelial dysfunction. In comparison, SGLT-2 inhibitors appear to improve ventricular loading conditions, reduce sympathetic nervous system activation, reduce cardiac fibrosis, reduce renal hypoxia and renal-cardiac signalling, reduce left ventricular mass and improve cardiac energetics. In this review, we summarize the potential mechanisms whereby GLP-1 receptor agonists and SGLT-2 inhibitors improve CV outcomes in patients with type 2 diabetes and highlight evidence for their use in populations without diabetes.
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Invited review. Series: Implications of the recent CVOTs in type 2 diabetes: Which patients for GLP-1RA or SGLT-2 inhibitor?
Dardano, A, Miccoli, R, Bianchi, C, Daniele, G, Del Prato, S
Diabetes research and clinical practice. 2020;:108112
Abstract
Large cardiovascular outcome trials (CVOTs) have lent support to a cardiovascular protection with the use of SGLT2-inhibitors (SGLT2is) and GLP1-Receptor Agonists (GLP1-RAs) in subjects with type 2 diabetes. These two classes of novel glucose lowering agents have been shown to have a similar effect on the risk reduction of Major Adverse Cardiovascular Events (MACE: nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality). Nonetheless, they may not be simply interchangeable. Rather, careful evaluation of all the results of CVOTs leads identification of different effects that may allow profiling of the ideal individuals with T2DM who may benefit most from the use of one or the other class of agents. These differences include effect on heart failure, stroke and diabetic kidney disease that have prompt recent guidelines and recommendation for the treatment of type 2 diabetes to suggest the preferential use of SGLT2is in those with evidence of heart failure and impaired kidney function, while both SGLT2i and GLP1-RAs with proven effect could be use in those with prevalent atherosclerotic cardiovascular disease. This review discusses all these elements of differentiation along with others that in the future may help establishing the best cardiorenal benefit for individuals with T2DM.
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10.
Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist.
Bucheit, JD, Pamulapati, LG, Carter, N, Malloy, K, Dixon, DL, Sisson, EM
Diabetes technology & therapeutics. 2020;(1):10-18
Abstract
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering hemoglobin A1c (HbA1c) and facilitating weight loss. Four agents in the GLP-1 RA class, albiglutide, liraglutide, dulaglutide, and semaglutide, also have cardioprotective effects. However, subcutaneous administration of these agents remains a major reason for their underutilization. A new coformulation of semaglutide with sodium N-[8-(2-hydroxybenzoyl) amino caprylate (SNAC) is the first oral GLP-1 RA reviewed by the U.S. Food and Drug Administration (FDA). The SNAC technology prevents destruction of semaglutide in the stomach and facilitates transcellular absorption through the gastric membrane enabling semaglutide to reach systemic circulation intact. The oral formulation of semaglutide was studied in the PIONEER trials, demonstrating similar efficacy to the presently available GLP-1 RAs with regard to HbA1c lowering and weight loss. Although the PIONEER 6 trial suggests positive effects on cardiovascular mortality with oral semaglutide, these benefits may not fully be appreciated until the completion of the SOUL trial.