Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status without Worsening Glycemia

Inclisiran, an investigational PCSK9-specific RNA silencing molecule with potential for a maintenance regimen of twice yearly dosing, significantly lowered LDL-C and PCSK9 in the dose-ranging ORION-1 trial. We report its efficacy and safety by diabetes status, and its impact on glycemia. ORION-1 randomized 501 persons with atherosclerosis (ASCVD) or ASCVD-risk equivalents, and high LDL-C despite maximally tolerated LDL-C lowering therapies, to inclisiran or placebo. Inclisiran significantly lowered LDL-C and PCSK9 similarly in persons with and without diabetes at day 180 (Table). Temporal A1C were similar in the placebo and incisiran arms (Figure). These data suggest that inclisiran is efficacious and does not worsen glycemia in persons with ASCVD or ASCVD-risk equivalents, regardless of their diabetes status, over 180 days.