Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which has been developed as once-weekly injection first for the treatment of type 2 diabetes (T2DM), then for the treatment of obesity. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. In the SURMOUNT programme, tirzepatide showed a marked reduction in body weight, never reached before with a drug, among people with obesity or overweight associated with complications linked to excess weight. Such weight loss was accompanied by an improvement of comorbidities (as sleep apnea syndrome) and cardiovascular risk factors. Two large cardiovascular outcome trials are ongoing in patients with T2DM (SURPASS-CVOT) and in patients with obesity (SURMOUNT-MMO).
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