Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Diabetes Care, Journal Year: 2018, Volume and Issue: 41(12), P. 2669 - 2701

Published: Oct. 5, 2018

The American Diabetes Association and the European for Study of convened a panel to update prior position statements, published in 2012 2015, on management type 2 diabetes adults. A systematic evaluation literature since 2014 informed new recommendations. These include additional focus lifestyle self-management education support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, surgical interventions, are recommended. With regards medication management, patients clinical cardiovascular disease, sodium-glucose cotransporter (SGLT2) inhibitor or glucagon-like peptide 1 (GLP-1) receptor agonist proven benefit is chronic kidney disease heart failure atherosclerotic an SGLT2 GLP-1 agonists generally recommended as first injectable medication.

Language: Английский

---

Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

New England Journal of Medicine, Journal Year: 2019, Volume and Issue: 381(9), P. 841 - 851

Published: June 11, 2019

Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available the subcutaneous form glucagon-like peptide-1 receptor agonist semaglutide but needed oral semaglutide.

Language: Английский

---

Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Diabetologia, Journal Year: 2018, Volume and Issue: 61(12), P. 2461 - 2498

Published: Oct. 4, 2018

Language: Английский

---

Glucagon-like peptide 1 (GLP-1)

Molecular Metabolism, Journal Year: 2019, Volume and Issue: 30, P. 72 - 130

Published: Sept. 30, 2019

Background: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential.Among the numerous metabolic effects of GLP-1 are glucose-dependent stimulation insulin secretion, decrease gastric emptying, inhibition food intake, increase natriuresis and diuresis, modulation rodent b-cell proliferation.GLP-1 also has cardio-and neuroprotective effects, decreases inflammation apoptosis, implications for learning memory, reward behavior, palatability.Biochemically modified enhanced potency sustained action, receptor agonists successfully in clinical use treatment type-2 diabetes, several GLP-1-based pharmacotherapies evaluation obesity.Scope review: In this review, we provide detailed overview on nature its pharmacology discuss therapeutic various diseases.Major conclusions: Since discovery, emerged as pleiotropic myriad functions that go well beyond classical identification an incretin hormone.The beneficial render interesting candidate development to treat obesity, neurodegenerative disorders

Language: Английский

---

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 385(6), P. 503 - 515

Published: June 25, 2021

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that under development for the treatment of type 2 diabetes. The efficacy safety once-weekly tirzepatide as compared with semaglutide, selective GLP-1 agonist, are unknown.

Language: Английский

---

GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 46, P. 101102 - 101102

Published: Oct. 14, 2020

GLP-1 receptor agonists (GLP-1 RAs) with exenatide b.i.d. first approved to treat type 2 diabetes in 2005 have been further developed yield effective compounds/preparations that overcome the original problem of rapid elimination (short half-life), initially necessitating short intervals between injections (twice daily for b.i.d.). To summarize current knowledge about agonist. At present, RAs are injected twice (exenatide b.i.d.), once (lixisenatide and liraglutide), or weekly weekly, dulaglutide, albiglutide, semaglutide). A oral preparation semaglutide, which has demonstrated clinical effectiveness close once-weekly subcutaneous preparation, was recently approved. All share common mechanisms action: augmentation hyperglycemia-induced insulin secretion, suppression glucagon secretion at hyper- euglycemia, deceleration gastric emptying preventing large post-meal glycemic increments, a reduction calorie intake body weight. Short-acting agents b.i.d., lixisenatide) reduced on overnight fasting plasma glucose, but maintain their effect during long-term treatment. Long-acting (liraglutide, exenatide, semaglutide) more profound effects glucose HbA1c, both background glucose-lowering combination basal insulin. Effects decrease over time (tachyphylaxis). Given similar, if not superior, HbA1c additional weight no intrinsic risk hypoglycemic episodes, GLP-1RAs recommended as preferred injectable therapy diabetes, even before However, can be combined (basal) either free- fixed-dose preparations. More agents, particular characterized by greater efficacy respect lowering well Since 2016, several cardiovascular (CV) outcome studies shown effectively prevent CV events such acute myocardial infarction stroke associated mortality. Therefore, guidelines particularly recommend treatment patients pre-existing atherosclerotic vascular disease (for example, previous events). The evidence similar lower-risk subjects is quite strong. sodium/glucose cotransporter-2 (SGLT-2) inhibitor reduces (with mainly driven heart failure complications), individual ischemic complications should guide choice may also help renal diabetes. Other active research areas field definition subgroups within population who benefit from RAs. These include pharmacogenomic approaches characterization non-responders. Novel indications outside 1 neurodegenerative diseases, psoriasis, being explored. Thus, 15 years initial introduction, become well-established class potential development growing impact treating potentially other diseases.

Language: Английский

---

Anti-obesity drug discovery: advances and challenges

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 21(3), P. 201 - 223

Published: Nov. 23, 2021

Enormous progress has been made in the last half-century management of diseases closely integrated with excess body weight, such as hypertension, adult-onset diabetes and elevated cholesterol. However, treatment obesity itself proven largely resistant to therapy, anti-obesity medications (AOMs) often delivering insufficient efficacy dubious safety. Here, we provide an overview history AOM development, focusing on lessons learned ongoing obstacles. Recent advances, including increased understanding molecular gut–brain communication, are inspiring pursuit next-generation AOMs that appear capable safely achieving sizeable sustained weight loss. The development therapies loss proved tremendously challenging. Müller et al. drug learned, challenges recent advances field.

Language: Английский

---

Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial

The Lancet, Journal Year: 2018, Volume and Issue: 392(10160), P. 2180 - 2193

Published: Oct. 4, 2018

Language: Английский

---

The Discovery and Development of Liraglutide and Semaglutide

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: April 12, 2019

The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts extend its half-life make it therapeutically effective in people type 2 diabetes (T2D). development short- then long-acting GLP-1 receptor agonists (GLP-1RAs) followed. Our article charts the analogs liraglutide and, subsequently, semaglutide. We examine chemistry employed designing semaglutide, human nonhuman studies used investigate their cellular targets pharmacological effects, ongoing investigations into new applications formulations these drugs. Reversible binding albumin was for systemic protraction optimal fatty acid linker combinations identified maximize while maintaining (GLP-1R) potency. GLP-1RAs mediate via this receptor, which is expressed pancreas, gastrointestinal tract, heart, lungs, kidneys brain. GLP-1Rs pancreas brain have been shown account respective improvements that are evident Both semaglutide also positively affect cardiovascular (CV) outcomes individuals T2D, although precise mechanism still being explored. Significant loss, through effect reduce energy intake, approval (3.0 mg) treatment obesity, indication currently under investigation Other include nonalcoholic liver disease (NASH) use oral formulation T2D. In summary, rational design has two analogs, made a vast contribution management T2D terms control, weight, blood pressure, lipids, beta-cell function CV outcomes. Furthermore, may provide additional benefits relation adherence. addition obesity NASH.

Language: Английский

---

Advances in oral peptide therapeutics

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 19(4), P. 277 - 289

Published: Dec. 17, 2019

Language: Английский

---