scholarly journals Oral semaglutide: the innovation in type 2 diabetes management

2021 ◽  
Vol 24 (3) ◽  
pp. 273-281
Author(s):  
M. V. Shestakova ◽  
M. Sh. Shamkhalova ◽  
G. R. Galstyan ◽  
L. A. Ruyatkina ◽  
L. A. Suplotova
Keyword(s):  
Diabetes Management ◽  
Daily Basis ◽  
Glucose Lowering ◽  
Oral Form ◽  
Clinical Program ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Clinical Trial Program ◽  
Dose Dependent

Oral semaglutide is the first-in-class glucagon-like peptide-1 receptor agonist available in the form of pills administered per os. PIONEER — the clinical trial program assessing the efficacy and safety of oral semaglutide — demonstrated the dose-­dependent efficacy of the drug: the reduction of up to -1,4% in terms of glucose-lowering effects and the decrease of up to 5 kg in terms of weight loss. Moreover, oral semaglutide is superior in this regard compared to empagliflozin 25 mg, liraglutide 1,8 mg and sitagliptin 100 mg according to the dedicated trials of clinical program. From the cardiovascular perspective oral semaglutide has been proven to be safe. Therapeutic concentration of semaglutide in oral form is reached under ­several conditions: taking tablets on a daily basis in a fasting state with up to half a glass of water and waiting 30 minutes before drinking, eating, or taking other drugs. Most frequent adverse events were GLP-1 associated gastrointestinal reactions (­nausea, vomiting and diarrhea), most of the events were transient and occurred generally during dose escalation.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

2021 ◽  
Vol 104 (11) ◽  
pp. 1850-1865
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Evidence Review ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Lowering Therapy ◽  
The Cost ◽  
Selection Of

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

scholarly journals Potential cardiovascular benefits of GLP-1 analogues: evidence and implications for type 2 diabetes management

2020 ◽  
pp. 24-29
Author(s):  
M Vally
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Paradigm Shift ◽  
Diabetes Management ◽  
Clinical Trial Data ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) analogues are an injectable therapy used in the management of type 2 diabetes. These drugs seem to reduce cardiovascular risk factors and clinical trial data seems to suggest that liraglutide and semaglutide reduce cardiovascular risk in patients with type 2 diabetes and concomitant atherosclerotic cardiovascular disease. The search for agents such as these (and SGLT2 inhibitors) that not only manage diabetes but also reduce cardiovascular risk has resulted in a paradigm shift in the way diabetes can be managed.

scholarly journals How glucagon-like peptide 1 receptor agonists work

2021 ◽  
Author(s):  
Christine Rode Andreasen ◽  
Andreas Andersen ◽  
Filip Krag Knop ◽  
Tina Vilsbøll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Reduce Body Weight ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Clinical Utilisation

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

scholarly journals Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

2003 ◽  
Vol 31 (3) ◽  
pp. 529-540 ◽  
Author(s):  
BD Green ◽  
VA Gault ◽  
MH Mooney ◽  
N Irwin ◽  
CJ Bailey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Biological Activities ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Glucose Lowering ◽  
Dpp Iv ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?

2010 ◽  
Vol 299 (1) ◽  
pp. E10-E13 ◽  
Author(s):  
Filip K. Knop
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Secretion ◽  
Postprandial Glucose ◽  
Glucose Lowering ◽  
Incretin Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.

scholarly journals The role of metformin in the light of the most recent Guidelines

2020 ◽  
Vol 23 (1) ◽  
pp. 61
Author(s):  
Corigliano, G.
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Newly Diagnosed ◽  
High Cardiovascular Risk ◽  
Glucose Lowering ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Moment

Metformin was introduced in the market about 60 years ago and is definitely the most used drug in people with type 2 diabetes mellitus at the moment. In fact, it has insulin-sensitizing properties, through which it provides not only doubtless glucose lowering effects but also some protection against ADRD and cancer and especially significant cardiovascular benefits. We hereby briefly review the literature behind the above mentioned extra-glycemic effects and, based on expected additional benefits, suggest to refrain from delaying metformin utilization in addition to first class drugs like inhibitors of type 2 sodiumglucose cotransport (SGLT-2i) and /or glucagon-like peptide 1 receptor agonists (GLP1-RA) in people at high cardiovascular risk with newly diagnosed type 2 diabetes. KEY WORDS metformin; diabetes mellitus; cardiovascular disease; ADRD; cancer

Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases

2019 ◽  
Vol 26 (2_suppl) ◽  
pp. 73-80 ◽  
Author(s):  
Francesco Prattichizzo ◽  
Lucia La Sala ◽  
Lars Rydén ◽  
Nikolaus Marx ◽  
Marc Ferrini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Receptor Agonist ◽  
Glucose Lowering ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications. Recent cardiovascular outcome clinical trials suggest that certain new glucose-lowering drugs are accompanied by additional cardioprotective properties. Indeed, selected glucagon-like peptide-1 receptor agonists have a proved cardiovascular benefit in terms of a reduced incidence of ischaemic events, while sodium/glucose co-transporter-2 inhibitors have also shown significant protection, with a striking effect on heart failure and renal endpoints. These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages. Furthermore, the new 2019 European Society of Cardiology guidelines in collaboration with the European Association for the Study of Diabetes recommend a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor in treatment-naive patients with type 2 diabetes mellitus with pre-existing cardiovascular disease or at high cardiovascular risk. Future research will disentangle the mechanisms underpinning these beneficial effects and will also establish to what extent these results are generalisable to the whole diabetes population. In the meantime, available evidence should prompt a wide diffusion of these two classes of drugs among patients with diabetes and cardiovascular disease. Here, we briefly summarise recent findings emerging from cardiovascular outcome clinical trials, discuss their impact on treatment algorithms and propose new possible approaches to improve our knowledge further regarding the cardiovascular effect of glucose-lowering medications.

scholarly journals Oral GLP-1 analogue: perspectives and impact on atherosclerosis in type 2 diabetic patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
José Francisco Kerr Saraiva ◽  
Denise Franco
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Diabetes Management ◽  
Plasma Lipids ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Risk Of Death ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

AbstractCardiovascular events related to atherosclerosis are responsible for high morbidity and mortality among patients with type 2 diabetes. Improvement in care, especially in early stages, is crucial. Oral semaglutide, a glucagon-like peptide 1 analogue, controls blood glucose and results in significant body weight loss in patients with type 2 diabetes. Beyond these well-known effects, an interesting aspect of this drug is its antiatherogenic activity, which should be further explored in clinical practice. This paper reviews the evidence related to oral semaglutide decreasing cardiovascular risk in patients with type 2 diabetes, focusing on the drug’s antiatherosclerotic properties. The glucagon-like peptide 1 analogue restores endothelial dysfunction, induces vasodilatation, and reduces plasma lipids. Oral semaglutide showed cardiovascular safety profile, with significant reduced risk of death from cardiovascular events. Based on current data, clinicians should consider oral semaglutide for type 2 diabetes management.

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