Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a randomized, double-blind, placebo-controlled trial

• DOI: 10.1126/scitranslmed.abl8503
• Publication Date: 2022-06-15T17:54:39Z
• Authors: Riccardo Pofi; Elisa Giannetta; Tiziana Feola; Nicola Galea; Federica Barbagallo; Federica Campolo; Roberto Badagliacca; Biagio Barbano; Federica Ciolina; Giuseppe Defeudis; Tiziana Filardi; Franz Sesti; Marianna Minnetti; Carmine D. Vizza; Patrizio Pasqualetti; Pierluigi Caboni; Iacopo Carbone; Marco Francone; Carlo Catalano; Paolo Pozzilli; Andrea Lenzi; Mary Anna Venneri; Daniele Gianfrilli; Andrea M. Isidori
• Keywords: Cyclic Nucleotide Phosphodiesterases, Type 5; Male; Ventricular Remodeling; Penile Erection; Phosphodiesterase 5 Inhibitors; Tadalafil; 3. Good health; diabetes; cardiomyopathy; inflammation; kidney; sex; gender; Kinetics; MicroRNAs; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Diabetes Mellitus, Type 2; Double-Blind Method; Erectile Dysfunction; Humans; Female; Carbolines

Cyclic GMP–phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) assess sex differences remodeling after PDE5 patients with diabetic cardiomyopathy. A total of 122 men and women (45 80 years) long-duration (>3 well-controlled 2 mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according echocardiographic signs remodeling. Patients randomly assigned (1:1) placebo or oral tadalafil (20 mg, once daily). The primary outcome was evaluate torsion change. Secondary outcomes cardiovascular, metabolic, immune, renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement (−3.40°, −5.96; −0.84, P = 0.011) fiber shortening (−1.19%, −2.24; −0.14, 0.027) women. could be explained cGMP concentrations pharmacodynamics. In both sexes, improved hsa-miR-199-5p expression, biomarkers cardiovascular remodeling, albuminuria, artery resistive index, circulating Klotho concentrations. Immune cell profiling revealed low-grade chronic inflammation: Classic CD14 ++ CD16 − monocytes reduced, Tie2 + increased. Nine (14.5%) had minor adverse reactions administration. Continuous offer strategy target cardiorenal complications T2DM, sex- tissue-specific responses. Further studies are needed confirm as markers for T2DM complications.