A novel glucagon-like peptide-1/glucagon receptor dual agonist exhibits weight-lowering and diabetes-protective effects

Zhou, Jie; Cai, Xingguang; Huang, Xun; Dai, Yuxuan; Sun, Lin; Zhang, Bo; Yang, Bo; Lin, Haiyan; Huang, Wenlong; Qian, Hai

doi:10.1016/j.ejmech.2017.07.046

Cited by 32 publications

(19 citation statements)

References 29 publications

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“…In animal models and non-human primates, GLP-1/glucagon agonists have shown potency to induce glycaemic control, weight loss and reduce hepatic fat content. 145 A novel GLP-1R/GCGR dual agonist used in diet-induced obese mice normalised glucose tolerance, improved adiposity and metabolic parameters, 146 suggesting that this combination could be potentially beneficial in patients with diabetes and possibly women with PCOS.…”

Section: Future Treatment Optionsmentioning

confidence: 99%

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

Abdalla

Deshmukh

Atkin

et al. 2020

Therapeutic Advances in Endocrinology

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.

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Section: Future Treatment Optionsmentioning

confidence: 99%

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

Abdalla

Deshmukh

Atkin

et al. 2020

Therapeutic Advances in Endocrinology

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“…Except from acting by enhancing the insulin production after meal, it also induces satiety through not yet clarified mechanisms. However, novel GLP-1 agonists are under study in order to lower the chance of hypoglycemic complications and increase the weight reduction potential (Srivastava and Apovian, 2018;Zhou et al, 2017). The centrally acting drugs for obesity are mainly from the group of sympathomimetics that increase the noradrenalin and dopamine levels and inhibit hunger signals by activation of the adrenergic mediation.…”

Section: Pharmacotherapymentioning

confidence: 99%

Causes and solutions to “globesity”: The new fa(s)t alarming global epidemic

Vasileva

Marchev

Georgiev

2018

Food and Chemical Toxicology

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Diverse groups of factors are leading to increased weight gain and obesity, such as certain genetic phenotypes, neuroendocrine disturbances, the administration of some drugs, behavioral, social and environmental factors. The progressively escalating rates of overweight and obesity worldwide have led to an introduction of a new term "globesity". Excessive accumulation of body fat and especially of visceral adipose tissue is the main predisposing factor for the development of metabolic syndrome and other obesity related co-morbidities. At the present moment only few pharmacotherapeuticals are used for long-term treatment of obesity acting on narrow target spectra, e.g. pancreatic and gastric lipase inhibition, acting as adrenomimetics or activating the satiety centers in hypothalamus. Plant-based medications that accelerate weight loss, proved to be safe, effective and widely available, would be a preferable alternative for anti-obesity treatments. As plant extracts are multi-component systems they could also act by more than one mechanism, including decreased lipid absorption, decreased energy intake, increased energy expenditure, decreased pre-adipocyte differentiation and proliferation, decreased lipogenesis and increased lipolysis. The current review gives a summary of the risk factors for obesity development and its characteristics consequences. Current treatment options, combining lifestyle changes and conventional treatment with commercial anti-obesity drugs have been described as well. Special emphasis on in vitro, in vivo and human studies, of potential medicinal plant extracts and phytochemicals, such as polyphenols, terpenoids, alkaloids, saponins, able to modulate the molecular pathways and gene/protein expressions related to obesity, have been highlighted.

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“…Additionally in 2017, a novel GLP-1R/GCGR dual agonist was developed with amino acid substitution at position 22, 23 and 25 by cysteine in glucagon and laurate maleimide conjugation to optimize the pharmacokinetic profile of this compound. In DIO mice, administration of 1000nmol/kg once every two days for a treatment period of one month normalized glucose tolerance, adiposity and improved plasma metabolic parameters, such as leptin, insulin and adiponectin [ 173 ].…”

Section: Unimolecular Polyagonists- a New Strategy For The Treatment mentioning

confidence: 99%

Gut hormone polyagonists for the treatment of type 2 diabetes

et al. 2018

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A novel glucagon-like peptide-1/glucagon receptor dual agonist exhibits weight-lowering and diabetes-protective effects

Cited by 32 publications

References 29 publications

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

Causes and solutions to “globesity”: The new fa(s)t alarming global epidemic

Gut hormone polyagonists for the treatment of type 2 diabetes

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