Why the study?
It was hypothesized that combining cardioprotective glucose-lowering drugs (SGLT2 inhibitors or GLP-1 receptor agonists) and statins is associated with lower risk of first-time ASCVD than using either drug alone.
Does the combination of cardioprotective glucose-lowering drugs and statins reduce the risk of first-time ASCVD compared to either drug alone in individuals with type 2 diabetes without preexisting ASCVD?
Does the combination of cardioprotective glucose-lowering drugs and statins reduce the risk of first-time ASCVD compared to either drug alone in individuals with type 2 diabetes without preexisting ASCVD?
In patients with type 2 diabetes without prior ASCVD, statins are associated with a substantially lower risk of first-time ASCVD than cardioprotective glucose-lowering drugs, and combining them does not appear to significantly lower risk beyond statins alone.
Answers are grounded in this paper and cite their sources.
Statin monotherapy may suffice for ASCVD prevention in T2D without prior events; leaves open whether adding SGLT2i/GLP-1RA confers benefit in RCTs.
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.
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Ternhamar et al. (2025) studied this question.
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