Peer-Reviewed Publication
Nat Commun2026April 4, 2026Journal Article
Real-world evidence for comparative safety of second-line antihyperglycemic agents in older adults with type 2 diabetes.
Chungsoo Kim1,2,3, Fan Bu4, Clair Blacketer5, Anna Ostropolets5, Talita Duarte-Salles6,7, Benjamin Viernes8, Thomas Falconer9, Andrea Pistillo6, Jing Li10, Can Yin10, Mui Van Zandt11, Paul Nagy12, Akihiko Nishimura13, Evan Minty14, Seng Chan You15, Mitsuaki Sawano2, Shoko Sawano2, Ja Young Jeon16, Arya Aminorroaya1, Lovedeep S Dhingra1, Aline F Pedroso1, Phyllis Thangaraj1, David A Dorr17, Nicole Pratt18, Kenneth K C Man19, Wallis C Y Lau20, Daniel R Morales21, Rohan Khera1,2, Martijn J Schuemie5, Patrick B Ryan5,9, George Hripcsak8,9, Harlan M Krumholz1,2, Marc A Suchard22,23, Yuan Lu24,25
1Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA.
2Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA.
3Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea.
4Department of Biostatistics, University of Michigan, Ann Arbor, USA.
5Johnson and Johnson, New Brunswick, USA.
6Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain.
7Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.
8VA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, USA.
9Department of Biomedical Informatics, Columbia University, New York, USA.
10Real World Solutions, IQVIA, Shanghai, China.
11Real World Solutions, IQVIA, Durham, USA.
12Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, USA.
13Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
14O'Brien Institute for Public Health, University of Calgary, Calgary, Canada.
15Department of Biomedicine Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.
16Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea.
17Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, USA.
18Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia.
19Research Department of Practice and Policy, UCL School of Pharmacy, London, USA.
20Usher Institute, University of Edinburgh, Edinburg, USA.
21Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, USA.
22VA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, USA. msuchard@ucla.edu.
23Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, USA. msuchard@ucla.edu.
24Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. y.lu@yale.edu.
25Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, USA. y.lu@yale.edu.
Abstract
As prescribing of newer antihyperglycemic agents expands, there remains limited comparative safety data for older adults-a population particularly vulnerable to adverse drug events and underrepresented in clinical trials. We conduct a multinational cohort study using nine databases from the U.S. and Europe. Among adults aged ≥65, we compare eighteen safety outcomes across four classes of second-li…
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