- |||||||||| Review, Journal: Alternative role of glucagon-like Peptide-1 receptor agonists in neurodegenerative diseases. (Pubmed Central) - Dec 6, 2022
Herein, we reviewed the recent progress, both in preclinical studies and clinical trials, regarding these clinically used GLP-1R agonists in aging-related neurodegenerative diseases, mainly AD and PD. We stress the pleiotropic characteristics of GLP-1R agonists as repurposing drugs to target multiple pathological mechanisms and for use in the future for these devastating neurodegenerative conditions.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Byetta (exenatide) / AstraZeneca, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Synthesis of the extracellular domain of GLP-1R by chemical and biotechnological approaches. (Pubmed Central) - Sep 23, 2022
As a proof-of-concept model, nGLP1-R was made by SPPS to form the purified full-length polypeptide chain, subjected to self-guided or spontaneous Cys pairing. However, the formation of correct SS-pairs was lagging behind any protocol in use support, and the bottleneck of large-scale protein production relies on the risky step of proper refolding, which is sometimes possible only if a suitable fusion partner effectively helps and catalysis of the correct disulfide formation.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Tresiba (insulin degludec) / Novo Nordisk, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: The role of Recent Pharmacotherapeutic Options on the Management of Treatment Resistant Type 2 Diabetes. (Pubmed Central) - Aug 10, 2022
These newer agents have substantial potential for lowering HbA1c through differing but complementary mechanisms. Use of new insulin analogs with GLP-1RA preparations either alone or in fixed-ratio combinations, such as glargine/lixisenatide and degludec/liraglutide, can also reduce the multiple drug adherence burden while improving glycemic control.
- |||||||||| Journal: Cardiovascular effects of incretins - focus on GLP-1 receptor agonists. (Pubmed Central) - Aug 5, 2022
Liraglutide, oral semaglutide and exenatide once weekly also reduced mortality...In the 2019 consensus report from EASD/ADA, GLP-1 RAs with demonstrated cardio-renal benefits (liraglutide, semaglutide and dulaglutide) are recommended after metformin to patients with established cardiovascular diseases or multiple cardiovascular risk factors...However, the results from cardiovascular outcome trials (CVOT) are very heterogeneous suggesting that some GLP-1RA are more suitable to prevent CVD than others. The CVOTs provide a basis upon which individual treatment decisions for patients with T2D and CVD can be made.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Byetta (exenatide) / AstraZeneca, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Association between variants in TCF7L2, CTRB1/2 and GLP-1R genes and response to therapy with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (Short Oral Discussion Area) - Jul 9, 2022 - Abstract #EASD2022EASD_969;
Materials and 191 adults with T2D (52% female, mean age and BMI 69.3±10.6 years and 35.8±5.7 kg/m 2 , respectively), who had been treated with liraglutide, exenatide, or lixisenatide for at least 6 months were included. Our findings do not suggest a role for the variants studied in affecting the response to GLP-1 RA treatment in Greek patients with T2D.
- |||||||||| Journal, HEOR: Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective. (Pubmed Central) - May 10, 2022
A budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide...These results were confirmed in the PSA. Semaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs.
- |||||||||| Review, Journal: The Effect of GLP-1 Receptor Agonists on Postprandial Lipaemia. (Pubmed Central) - May 6, 2022
GLP-1 RAs have consistent beneficial effects on postprandial lipaemia with most of the data coming from studies with exenatide and liraglutide. Reduction of postprandial lipaemia might be one of the mechanisms behind the pleiotropic effects of GLP-1 RAs.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Review, Journal, Adverse drug reaction: Adverse drug reactions of GLP-1 agonists: A systematic review of case reports. (Pubmed Central) - Apr 1, 2022
Gastrointestinal problems, particularly pancreatitis was the more frequently reported adverse drug reaction associated with GLP-1 agonist. The most adverse drug reactions were observed with liraglutide and exenatide.
- |||||||||| Retrospective data, Review: Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis. (Pubmed Central) - Feb 16, 2022
Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference...Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits...When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Retrospective data, Journal: GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs. (Pubmed Central) - Feb 8, 2022
This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464). GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
THE EFFECT OF GLP-1 AGONISTS IN PATIENTS WITH TYPE 2 DIABETES ON ALL-CAUSE MORTALITY AND CARDIOVASCULAR MORTALITY: AN UPDATED META-ANALYSIS OF 44 RANDOMIZED CONTROLLED TRIALS (Poster Hall_Hall C) - Jan 28, 2022 - Abstract #ACC2022ACC_5405;
Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar and EBSCO CINAHL were searched (from inception to September 2021) for randomized controlled trials reporting the relationship between GLP-1 agonists (including albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide) and all-cause and cardiovascular mortality. Our results suggest that use of GLP-1 Agonists in patients with type II diabetes was associated with lower risk of all-cause and cardiovascular mortality over follow up of greater than 1 year.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
ASSOCIATION OF GLP-1 AGONISTS WITH ARRHYTHMIAS AND SUDDEN CARDIAC DEATH IN PATIENTS WITH TYPE 2 DIABETES: A META-ANALYSIS OF 27 RANDOMIZED CONTROLLED TRIALS (Poster Hall_Hall C) - Jan 28, 2022 - Abstract #ACC2022ACC_2455;
We searched databases including Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar and EBSCO CINAHL, from inception to September 2021, for randomized controlled trials reporting the relationship between GLP-1 agonists (including albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide) and atrial and ventricular arrhythmias and sudden cardiac death. Our results suggest that use of GLP-1 agonists is not associated with increased risk of atrial and ventricular arrhythmias and sudden cardiac death over long-term follow up of greater than 52 weeks.
- |||||||||| Rybelsus (semaglutide oral) / Novo Nordisk, Ozempic (semaglutide SC once-weekly) / Novo Nordisk, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Clinical, Review, Journal: Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6. (Pubmed Central) - Jan 8, 2022
P3
Surprisingly, CV and all-cause mortality were significantly reduced by oral semaglutide in PIONEER 6...Findings from SUSTAIN 6 and PIONEER 6 fall within the spectrum reported with other GLP-1RA CVOTs: noninferiority vs. placebo for major CV events was seen with lixisenatide and exenatide extended-release, while superiority was demonstrated with liraglutide, albiglutide, and dulaglutide...The exact mechanism(s) remains to be characterized, but appears to be mainly linked to anti-atherosclerotic effects. Further research is needed to elucidate the relevant mechanisms for CV benefits of GLP-1RAs.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Glucagon-like peptide-1 receptor agonists in type 2 diabetes and long-term complications: FOCUS on retinopathy. (Pubmed Central) - Jan 1, 2022
This response was shown mainly in people with established cardiovascular disease, except for the REWIND trial, in which a majority of people without prior cardiovascular disease was included (69%). In those trials, in addition to the macrovascular benefits, GLP-1RAs also reduced some microvascular events; there was a reduction in a composite kidney outcome including macroalbuminuria [hazard ratio 0.83 (95% CI 0.78-0.89)] [1].
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Effect of anti-hyperglycemic drugs on endoplasmic reticulum (ER) stress in human coronary artery endothelial cells. (Pubmed Central) - Dec 25, 2021
High-dextrose and TM increased IRE1α and PERK phosphorylation and ATF6 and GRP78 expression, while treatment with metformin, liraglutide (a GLP-1 receptor agonist) and dapagliflozin (a SGLT-2 inhibitor), suppressed IRE1α and PERK phosphorylation as well as ATF6 and GRP78 expression. The cardioprotective effects of metformin, some of the GLP-1 receptor agonists and SGLT2 inhibitors may be partly related to their ability to reduce ER stress.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Kinetic control of Phytic acid/Lixisenatide/Fe (III) ternary nanoparticles assembly process for sustained peptide release. (Pubmed Central) - Dec 25, 2021
Moreover, this sustained peptide delivery system demonstrated a repeatable hypoglycemic effects and significantly suppressed the pathological damage of major organs following multiple injection. This sustained peptide delivery system with aqueous, facile and reproducible preparation process possesses good biocompatibility, tunable release kinetics, and prolonged hypoglycemic effects, portending its great translational potential in the chronic disease treatment.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Clinical, Journal: GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients. (Pubmed Central) - Dec 16, 2021
A number needed to treat under 50 is required to avoid one MACE in five years. These benefits have led to important changes in the Clinical Practice Guidelines and in the care of our patients with T2DM.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Clinical, Retrospective data, Review, Journal, Adverse events: Association of Glucagon-like Peptide 1 Analogs and Agonists Administered for Obesity with Weight Loss and Adverse Events: A Systematic Review and Network Meta-analysis. (Pubmed Central) - Dec 10, 2021
These benefits have led to important changes in the Clinical Practice Guidelines and in the care of our patients with T2DM. Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide ≥1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide ≤1.8mg; -4.49kg (-5.26 to -3.72) with liraglutide >1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ 50%) in WL and AEs reflected magnitude, not direction of effect.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. (Pubmed Central) - Nov 21, 2021
At present, GLP-1 RAs are injected twice daily (exenatide b.i.d.), once daily (lixisenatide and liraglutide), or once weekly (exenatide once weekly, dulaglutide, albiglutide, and semaglutide)...Novel indications for GLP-1 RAs outside type 2 diabetes, like type 1 diabetes, neuro-degenerative diseases, and psoriasis, are being explored. Thus, within 15 years of their initial introduction, GLP-1 RAs have become a well-established class of glucose-lowering agents which has the potential for further development and growing impact for the treatment of type 2 diabetes and potentially other diseases.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Preclinical, Journal: Insulin secretion decline in Walker-256 tumor-bearing rats is early, follows the course of cachexia, and is not improved by lixisenatide. (Pubmed Central) - Nov 7, 2021
In consistency, in vivo treatment with lixisenatide (50 μg kg, SC, once daily, for 6 days) visually increased insulinemia of healthy fasted rats, but did not prevent hypoinsulinemia of tumor-bearing rats. In conclusion, Walker-256 tumor-bearing rats showed early decline (2 days of tumor) of insulin secretion, which followed the cachexia course (6 and 12 days of tumor) and was not improved by lixisenatide, evidencing that this insulin secretagogue, used to treat type 2 diabetes, does not have beneficial effect in cancer bearing-rats.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Clinical, Journal: Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues. (Pubmed Central) - Oct 27, 2021
In this review, we discuss the available evidence from randomized controlled trials (RCTs) analyzing the cardiovascular effects of various GLP-1 RAs with the aim of comparing individual drugs. We have also summarized the general aspects of GLP-1RAs that can be applied in clinical practice.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Evidence for pathophysiological commonalities between metabolic and neurodegenerative diseases. (Pubmed Central) - Oct 13, 2021
This is a proof of concept that this approach is viable and that drug treatment affects the main drivers of the disease and does not just modify the symptoms. It demonstrates that this new research area is a promising and fertile space for the development of novel treatments for neurodegenerative diseases.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Retrospective data, Review, Journal: Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials. (Pubmed Central) - Aug 26, 2021
This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.
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