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  • Efficacy and safety of high...
    De Block, Christophe E. M.; Dirinck, Eveline; Verhaegen, Ann; Van Gaal, Luc F.

    Diabetes, obesity & metabolism, 20/May , Volume: 24, Issue: 5
    Journal Article

    Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high‐risk individuals. With currently available GLP‐1 RAs, 51%‐79% of subjects achieve an HbA1c target of less than 7.0% and 4%‐27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms ‘glucagon‐like peptide‐1 receptor agonist’, ‘glucagon receptor agonist’, ‘glucose‐dependent insulinotropic peptide’, ‘dual or co‐agonist’, and ‘tirzepatide’. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high‐dose GLP‐1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high‐dose GLP‐1 RAs or tirzepatide, respectively. The glucose‐ and weight‐lowering effects of the GLP‐1/glucagon RA cotadutide equal those of liraglutide 1.8 mg. Gastrointestinal side effects of high‐dose GLP‐1 RAs and co‐agonists occurred in 30%‐70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high‐dose GLP‐1 RAs and the dual GLP‐1/glucose‐dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15‐mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied.