Effects of glucagon‐like peptide‐1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials

Abstract

Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo-controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, ≥25-<30, ≥30-<35 and ≥35 kg/m 2), and CV and kidney outcomes with GLP-1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; P interaction = .02); otherwise, there was no statistical heterogeneity for either GLP-1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed.

GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects

“…Importantly, controlling inflammation is believed to contribute in the prevention of cardiovascular diseases ( 123 ). In one study, liraglutide and semaglutide were reported to mitigate the development of plaque lesions by changing the inflammatory pathway in a mouse model of AS ( 124 ). Besides, GLP-1RAs might be driven by anti-inflammatory mechanisms to inhibit the formation of macrophage foam cells and thus slow down the pathological processes of AS ( 125 , 126 ).…”

Impact of Obesity in Kidney Diseases

“…A significant decrease in albuminuria, new onset of persistent proteinuria, and no progression of eGFR decline have been reported in diabetic patients. SUSTAIN-6 with semaglutide [96], another member of the GLP1 agonist class, reduces the risk of composite renal outcome largely driven by persistent proteinuria. However, Dulaglutide in the AWARD-7 [97] did not find differences in the reduction of albuminuria.…”

Neues zu Hypertonie und Diabetes

“…Im Jahr 2020 wurde die EMPEROR-Reduced-Studie publiziert, die ausschließlich herzinsuffiziente Patienten mit NYHA-Stadien II, III oder IV mit einer Ejektionsfraktion ≤ 40 % mit und ohne Typ‑2-Diabetes einschloss. Die Probanden wurden neben der Standardtherapie entweder mit Empagliflozin 10 mg/Tag oder Plazebo behandelt [ 26 ]. Der primäre Endpunkt war eine Kombination von kardiovaskulärem Tod oder Hospitalisierung wegen sich verschlechternder Herzinsuffizienz.…”