Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Deepak L. Bhatt, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Megan Loy, Garen Manvelian, Robert Pordy, Harvey D. White, Philippe Gabriel Steg, ODYSSEY OUTCOMES Committees and Investigators, Shaun Goodman, Robert Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew Roe, Kenneth W. Mahaffey, Jay M. EdelbergCorinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean François Tamby, Philip Aylward, H. Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan Carlos Prieto, Huo Yong, Patricio Lopez-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo-Soo Kim, Sang Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, M. Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony Dalby, José Tuñón, H. Asita de Silva, Emil Hagstrom, Ulf Landmesser, Christian Muller, Chern En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Matthew T. Roe, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric Sijbrands, Pierluigi Tricoci, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, Kong David F, Sergio Leonardi, Linda Lillis, Renato D. Lopes, David J. Maron, Kenneth W. Mahaffey, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, Matthew T. Roe, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia Schiavi, MARCELO GARRIDO, Andrés F. Alvarisqueta, Sonia A. Sassone, ANSELMO PAULINO BORDONAVA, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, LEONARDO NOVARETTO, Miguel Angel Hominal, Oscar Montana, ALBERTO CACCAVO, Oscar Gomez Vilamajo, Alberto J. Lorenzatti, L.R. Cartasegna, Gustavo A. Paterlini, Ignacio J Mackinnon, G. D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio OE Bono, Adrian Hrabar, Julio A. Vallejos, Rodolfo Andres Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar Zaidman, Maria E. Giuliano, Ricardo Dario Dran, Marisa Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R. Colombo, A. G. Liberman, Victorino Fuentealba, Hector Lucas Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben Omar Garcia Duran, Horacio G. Cestari, Hugo A Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon Waites, Nicholas Collins, Allan Soward, Philip Aylward, Chris LS Hii, James Shaw, Margaret Arstall, John Horowitz, D. Ninio, James F. Rogers, David Colquhoun, Romulo E.Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam Lehman, Constantine Aroney, Steve G Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, H. Drexel, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Peter Sinnaeve, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mirza Dilic, Azra Durak-Nalbantic, Mehmed Kulic, Dusko Vulic, Adis Muslibegovic, Boris Goronja

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

Original languageEnglish
Pages (from-to)1219-1227
Number of pages9
JournalDiabetes Care
Volume44
Issue number5
Early online date15 Mar 2021
DOIs
Publication statusPublished - May 2021

Keywords

  • lipoprotein(a)
  • Type 2 Diabetes
  • Alirocumab
  • PCSK9 inhibitors

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