Introduction and Objective: Evaluate the effect of semaglutide (sema) on COVID-19-related complications and all-cause death. Methods: SELECT (n=17,604), FLOW (n=3533), and SOUL (n=9650) randomized participants (pts) with ASCVD/overweight/obesity without T2D (SELECT), T2D/CKD (FLOW), and T2D+ASCVD and/or CKD (SOUL), to sema vs placebo (pbo). Mean follow-up ranged 3.3-4 years, spanning the COVID-19 pandemic (53% of pts enrolled pre-Feb 2, 2020). Cause of death was adjudicated. Reported COVID-19-related infections, SAEs, and hospitalizations, and COVID-19-related deaths were analyzed. Results: Of 2444 deaths, 1398 (57.2%) were CV and 1046 (42.7) were non-CV, including 338 (13.8%) COVID-19 related deaths. Sema vs pbo reduced all-cause death (1130 vs 1314; HR 0.85 [CI 0.78, 0.92; p0.001), CV death (647 vs 751; 0.85 0.77, 0.95; p=0.003), and non-CV death (483 vs 563; 0.85 0.75, 0.96; p=0.008). Sema reduced the incidence of COVID-19 infections (3542 vs 3685, HR 0.95; p=0.018), COVID-19-related SAEs (605 vs 749, HR 0.80; p0.001), COVID-19-related hospitalizations (577 vs 705, HR 0.81; p0.001), and COVID-19-related deaths (141 vs 197, HR 0.71; p=0.002; Fig). There was no heterogeneity in COVID outcomes by study. Conclusion: In addition to reducing the risk of death across multiple studies, sema reduced the risk of COVID-19 and its complications, which is notable and warrants further investigation. Disclosure B. Scirica: Research Support; Current; Amgen Inc., Novo Nordisk, Merck Current; Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen Inc., Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim International GmbH. Other - Consultant and clinical trial support; Current; Corcept Therapeutics. Consultant; Ended; Dexcom, Inc. Consultant; Current; Eli Lilly and Company. Consultant; Ended; embecta. Consultant; Current; General Medicines Inc. Other - Consultant and clinical trial support; Current; GentiBio. Consultant; Ended; Insulet Corporation. Consultant; Current; Kayothera. Other - Consultant and stock options; Current; Metsera. Other - Expert witness; Ended; Medtronic. Other - Consultant and investigator; Current; Novo Nordisk. Consultant; Current; Recordati S.p.A, Sparrow Pharmaceuticals. Consultant; Ended; Tandem Diabetes Care, Inc. Consultant; Current; Vertex Pharmaceuticals Incorporated, vTv Therapeutics, Zealand Pharma A/S. A. Catarig: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. O.K. Jeppesen: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. A.M. Lincoff: Consultant; Current; Novo Nordisk, Eli Lilly and Company. Stock/Shareholder; Current; Canary Cure. Research Support; Current; Novartis AG. Consultant; Ended; Alnylam Pharmaceuticals, Inc., Amgen Inc., Ardelyx, Brainstom Cell, Capricor, Johnson Current; Novo Nordisk, Lilly, Boehringer Ingelheim International GmbH. Consultant; Ended; NewAmsterdam. Consultant; Current; Metsera, Amgen Inc., Novartis AG, Lexicon Pharmaceuticals, Inc. Consultant; Ended; Neurotronic. Consultant; Current; Kailera. V. Perkovic: Consultant; Current; AstraZeneca, Bayer AG, Biogen, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., GlaxoSmithKline plc., Incyte, Janssen Global Services, LLC, Novo Nordisk, Novartis Pharmaceuticals Corporation, Otsuka America Pharmaceutical, Inc., Tricida, Inc., Vifor Pharma Management Ltd., Minerlays, Guard Therapeutics, Shanxi Micot, Travere. R. Pratley: Consultant; Current; Lilly USA LLC. Research Support; Current; National Institutes of Health, Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Novo Nordisk. Consultant; Current; Pfizer Inc., Recordati Rare Diseases Inc., Regeneron Pharmaceuticals Inc., Response Pharmaceuticals, Rona Therapeutics Ltd. Research Support; Current; Sanofi. Consultant; Current; Scholar Rock Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Sun Pharmaceutical Industries Ltd. Consultant; Current; Third Rock Ventures, Verdiva Bio Dev Limited. Research Support; Current; AstraZeneca AB, Boehringer Ingelheim International GmbH, Abbott Laboratories. Consultant; Current; Abbott Laboratories, AbbVie Inc. Other - Consulting; stock options; Current; Altanine, Inc. Consultant; Current; Amgen Inc., AstraZeneca Pharmaceuticals LP. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Bayer AG, Bayer HealthCare Pharmaceuticals Inc. Research Support; Current; Biomea Fusion. Consultant; Current; Boehringer Ingelheim Pharmaceuticals Inc., Carmot Therapeutics, Inc., Corcept Therapeutics. Research Support; Current; Dompé, Eli Lilly and Company. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Eli Lilly and Company. Research Support; Current; Endogenex Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Endogenex Inc. Consultant; Current; F. Hoffmann-La Roche Ltd. Research Support; Current; Fractyl Health, Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Gasherbrum Bio Inc., Genprex. Consultant; Current; Hanmi Pharm. Co., Ltd. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Intas Pharmaceuticals Ltd. Research Support; Current; Lexicon Pharmaceuticals, Inc. Consultant; Current; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Current; Lilly USA LLC. S. Stensen: Employee; Current; Novo Nordisk A/S. M. Tran: None. D. Ryan: Advisory Panel; Current; Abbvie, Altimmune, Amgen, AstraZenica, Boehringer Ingelheim, Biohaven, Carmot/Roche/Genentech. Advisory Panel; Ended; eMed, Fractyl, Nestle. Consultant; Current; Pfizer, Source Bio, Protagonist, PPD, Regeneron, Regor. Advisory Panel; Current; Currax, Structure Therapeutics, Tenvie, Kailera. Speaker's Bureau; Current; LIlly, Novo Nordisk,. Other - I am a consultant to both and received stock options and consulting fees.; Current; Calibrate, Epitomee. Other - Data Monitoring Committee member; Current; CinRx, Rhythm, Lilly. Advisory Panel; Current; Viking, Weight Watchers, Wonder Health, Zealand. Other - ! received non-negotiable stock options from these companies years ago and have not worked for them in years.; Ended; Roman, Scientific Intake. Funding SELECT, FLOW, and SOUL Trials were supported by NovoNordisk A/S
SCIRICA et al. (Fri,) studied this question.