Title : Dual GIP/GLP-1 receptor stimulation in treatment of type 2 diabetes mellitus – The ground-breaking 'twincretin' approach
The prevalence of diabetes and obesity is an increasing worldwide problem, and is referred to as the twin epidemics. In the physiological context, today we know that native glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are incretin hormones that stimulate insulin secretion and decrease glucagon secretion. GIP also has a role in nutrient and energy metabolism, while GLP-1 in addition delays gastric emptying, suppresses appetite and improves state of being sated. Accordingly, glucagon-like peptide 1 aimed pharmacotherapy is a confirmed treatment alternative for the management of type 2 diabetes mellitus (T2DM) and is suggested early in the treatment protocol due to glycaemic efficacy, weight reduction and beneficial cardiovascular outcomes. Glucose-dependent insulinotropic polypeptide, in contrast, was thought to have no potential as a glucose-lowering therapeutic approach. However, co-infusion of GLP-1 and GIP was shown to exhibit a synergetic effect, resulting in notably increased insulin response with preventing further buildup of glucagon. These clarifications have led to the development of a dual GIP/GLP-1 receptor agonist tirzepatide, functionally recognized as a ‘twincretin’. Tirzepatide is a recently registered, and a 'first-in-class' novel dual GIP/GLP-1 receptor agonist with potent glucose lowering and weight loss actions. It improves glycaemic control in adults with T2DM, as an adjunct to diet and exercise with an acceptable safety profile. Given the previous facts, the main objectives of this presentation will be to clarify pharmacological properties of tirzepatide, including pharmacodynamics, pharmacokinetics, indications and contraindications for use, adverse drug reactions, as well as the most important drug interactions. This will provide a better understanding of this ground-breaking drug for T2DM, and most likely obesity management, thus helping clinicians in appropriate prescribing and its adequate clinical use.