[A new era for incretins : from GLP-1 receptor agonists to co-agonists and poly-agonists].

Sep 12, 2024Revue medicale de Liege

New developments in incretin drugs: from GLP-1 activators to combined and multi-target treatments

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Abstract

Tirzepatide showed a remarkable improvement in glucose control for patients with type 2 diabetes in the SURPASS program.

GLP-1 receptor agonists improve glucose control without causing low blood sugar and promote weight loss.
These agonists also protect against cardiovascular disease and reduce the risk of heart failure and chronic kidney disease in people with type 2 diabetes.
Co-infusion of GIP and GLP-1 did not further reduce hyperglycemia compared to GLP-1 alone.
New co-agonists targeting GIP and GLP-1 receptors are in development, which may leverage the benefits of glucagon on energy expenditure and liver metabolism.
These developments could play a role in managing obesity and its metabolic complications, including type 2 diabetes and liver steatosis.

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Incretin gut hormones, especially glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), raise a huge interest in diabetology. GLP-1 receptor agonists have gained a privileged role in the management of type 2 diabetes (T2D). They improve glucose control without inducing hypoglycaemia, while promoting weight loss. Furthermore, they protect people with T2D against atherosclerotic cardiovascular disease and contribute to reduce the risk of heart failure and chronic kidney disease, two other common complications of T2D. A recent innovation consists in the development of co-agonists that target both GIP and GLP-1 receptors. Whereas the co-infusion of GIP and GLP-1 failed to further reduce hyperglycaemia of T2D compared to GLP-1 single infusion, tirzepatide, an original dual unimolecular biaised GIP/GLP-1 agonist, showed a remarkable improvement of glucose control in the SURPASS programme in patients with T2D. Consequently, it is now commercialized in many countries for the management of T2D. GLP-1/glucagon (GCG) co-agonists and GIP/GLP-1/GCG poly-agonists are currently in development, aiming to benefit from the favourable effects of GCG on energy expenditure and liver lipid metabolism, while mitigating the hyperglycaemic effects of this hormone thanks to balanced effects of GLP-1 and/or GIP. They might occupy in the future an interesting place in the management of obesity and its metabolic complications among which T2D and liver steatosis.

[A new era for incretins : from GLP-1 receptor agonists to co-agonists and poly-agonists].

Abstract

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