Cardioprotective glucose-lowering drugs, statins, and risk of first-time atherosclerotic cardiovascular disease in Denmark: a nationwide cohort study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: We hypothesized that combining cardioprotective glucose-lowering drugs, i.e. sodium-glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists, and statins is associated with lower risk of first-time atherosclerotic cardiovascular disease (ASCVD) than using either drug alone. Methods: We identified and followed individuals in Denmark with type 2 diabetes and without preexisting ASCVD from 2012 to 2021. In an active comparator design, individuals initiating a cardioprotective glucose-lowering drug or a dipeptidyl peptidase-4 inhibitor ± statin were compared: i) dipeptidyl peptidase-4 inhibitor (N = 12,298/59,795; 21%), ii) cardioprotective glucose-lowering drug (N = 16,357/59,795; 27%), iii) dipeptidyl peptidase-4 inhibitor plus statin (N = 14,823/59,795; 25%), and iv) cardioprotective glucose-lowering drug plus statin (N = 16,317/59,795; 27%). Also, in a time-varying design with annually updated covariates we compared: i) no cardioprotective drug (N = 113,669/277,747; 41%), ii) cardioprotective glucose-lowering drug (N = 12,225/277,747; 4%), iii) statin (138,405/277,747; 50%), and iv) cardioprotective glucose-lowering drug plus statin (N = 13,448/277,747; 5%). The primary outcome was ASCVD (myocardial infarction, coronary revascularization, stroke, peripheral arterial disease, or coronary death). Findings: In the active comparator and time-varying cohorts during mean follow-ups of 3.2 and 5.9 years, 2546/59,795 (4%) and 28,044/277,747 (10%) developed ASCVD. In the active comparator cohort, multivariable adjusted hazard ratios of ASCVD were 0.87 (95% confidence interval: 0.76-0.98) for cardioprotective glucose-lowering drug, 0.69 (0.63-0.77) for statin, and 0.64 (0.56-0.73) for combined treatment compared with dipeptidyl peptidase-4 inhibitor. Corresponding values in the time-varying cohort were 0.94 (0.89-1.01), 0.70 (0.68-0.72), and 0.67 (0.64-0.70), respectively. Interpretation: In individuals with type 2 diabetes without preexisting ASCVD, statin was associated with substantially lower risk of ASCVD than cardioprotective glucose-lowering drug, while combination of the two drug classes was associated with similar ASCVD risk as statin alone. Funding: Danish Cardiovascular Academy and Danish Heart Foundation.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,930
Funders: Hjerteforeningen, Herlev Hospital, Novo Nordisk, Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond, Danmarks Frie Forskningsfond, Overlæge Johan Boserup og Lise Boserups Legat, Direktør Jacob Madsen og Hustru Olga Madsens Fond, Novo Nordisk Fonden, Beckett-Fonden, Danmarks Frie Forskningsfond, Danish Cardiovascular Academy
OpenAlex ID: W4415306107