[Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity].

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.

Cardiovascular and renal effects of the combination therapy of a GLP-1 receptor agonist and an SGLT2 inhibitor in observational real-life studies.

Background: Combining a glucagon-like peptide-1 receptor agonist (GLP-1RA) and an sodium-glucose cotransporter 2 inhibitor (SGLT2i) improved cardiovascular (and renal) prognosis compared to either monotherapy in several post-hoc exploratory analyses of randomized controlled trials (RCTs) versus placebo carried out in patients with type 2 diabetes (T2DM) and high cardiovascular/renal risk. The aim of the present work is to verify if such a benefit of the combined therapy is also present in real-life clinical practice.

Methods: An extended search of the literature was performed to select observational retrospective studies that compared cardiovascular and/or renal outcomes in patients with T2DM treated with a GLP-1RA/SGLT2i combination versus patients treated with either GLP-1RA monotherapy or SGLT2i monotherapy, in addition to standard of care therapy.

GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven efficacy and safety in randomized clinical trials and observational real-life studies. Besides improving glucose control, reducing body weight, and lowering arterial blood pressure (surrogate endpoints), the breakthroughs were the demonstration of a significant reduction in cardiovascular and renal events in patients with type 2 diabetes at high risk. GLP-1RAs reduce events linked to atherogenic cardiovascular disease (especially ischemic stroke) and also renal outcomes (FLOW trial with semaglutide), with a limited effect on heart failure.