New drugs for the treatment of diabetes mellitus

Bailey, Clifford J.

doi:10.1002/9781118387658.ch47

Cited by 3 publications

(3 citation statements)

References 44 publications

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“…However, the in-vivo effects of most of these compounds are too generalised to specifically target β cells and few have progressed in development. 10…”

Section: Small Molecule Insulin Releasersmentioning

confidence: 99%

“…Other inhibitors of glucagon secretion (eg, somatostatin analogues) have not been suitable for glucose-lowering in type 2 diabetes, mainly because of interference with the counter-regulatory response to hypoglycaemia, which is already defective in most patients. 10 Despite many accounts in the medical literature of glucagon receptor antagonists over more than 20 years, 33 few have progressed beyond initial clinical trials. 34,35 Unwanted effects on liver function have been described with some glucagon receptor antagonists, and glucagon receptor antagonism could possibly cause compensatory hyperglucagonaemia and rebound hyperglycaemia if treatment is not maintained.…”

Section: Glucagon Secretion and Actionmentioning

confidence: 99%

“…Provision of substrates for individual steps in the post-receptor pathways (eg, administration of the chiroinositol analogue pinitol enables signalling through phosphatidylinositol 3-kinase) is another approach under investigation. 10…”

Section: Reviewmentioning

confidence: 99%

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Future glucose-lowering drugs for type 2 diabetes

Bailey

Tahrani

Barnett

2016

The Lancet Diabetes & Endocrinology

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The multivariable and progressive natural history of type 2 diabetes limits the effectiveness of available glucose-lowering drugs. Constraints imposed by comorbidities (notably cardiovascular disease and renal impairment) and the need to avoid hypoglycaemia, weight gain, and drug interactions further complicate the treatment process. These challenges have prompted the development of new formulations and delivery methods for existing drugs alongside research into novel pharmacological entities. Advances in incretin-based therapies include a miniature implantable osmotic pump to give continuous delivery of a glucagon-like peptide-1 receptor agonist for 6-12 months and once-weekly tablets of dipeptidyl peptidase-4 inhibitors. Hybrid molecules that combine the properties of selected incretins and other peptides are at early stages of development, and proof of concept has been shown for small non-peptide molecules to activate glucagon-like peptide-1 receptors. Additional sodium-glucose co-transporter inhibitors are progressing in development as well as possible new insulin-releasing biological agents and small-molecule inhibitors of glucagon action. Adiponectin receptor agonists, selective peroxisome proliferator-activated receptor modulators, cellular glucocorticoid inhibitors, and analogues of fibroblast growth factor 21 are being considered as potential new approaches to glucose lowering. Compounds that can enhance insulin receptor and post-receptor signalling cascades or directly promote selected pathways of glucose metabolism have suggested opportunities for future treatments. However, pharmacological interventions that are able to restore normal β-cell function and β-cell mass, normalise insulin action, and fully correct glucose homoeostasis are a distant vision.

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“…However, the in-vivo effects of most of these compounds are too generalised to specifically target β cells and few have progressed in development. 10…”

Section: Small Molecule Insulin Releasersmentioning

confidence: 99%