Timing of Antidiabetic Medication Initiation and Risk of Cardiovascular Events and Mortality
Hwa Yeon Ko, Ju-Young Shin, Kyungyeon Jung, Sungho Bea, Bin Hong, Yunha Noh, Jae Hyun Bae, Soo Heon Kwak, Young Min Cho, Ga-young Lim, Jiin Ahn, Seungho Ryu, Ju Hwan Kim, Yoosoo ChangImportance
Among individuals who meet the diagnostic threshold for type 2 diabetes (T2D), timely initiation of antidiabetic medication (ADM) is essential for lowering long-term cardiovascular risk.
Objective
To estimate the association between ADM initiation timing—specifically within 3, 6, or 12 months—and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among individuals newly meeting diagnostic criteria for T2D.
Design, Setting, and Participants
This cohort study used target trial emulation to analyze health screening data linked to health insurance claims in Korea (2013-2022) using a clone-censor-weight approach. Participants were adults with newly detected glycated hemoglobin (HbA 1c ) of 6.5% or greater or fasting plasma glucose of 126 mg/dL or greater. Data analysis was conducted from January to August 2025.
Exposures
Eligible participants were cloned into 4 treatment strategies: ADM initiation within 3, 6, or 12 months or no initiation within 12 months (strategy 1, 2, 3, and control, respectively).
Main outcomes and Measures
Five-year absolute risk difference (RD) and risk ratio (RR) of 3-point MACE (stroke, myocardial infarction, and all-cause mortality) and all-cause mortality were estimated using Kaplan-Meier survival probabilities along with 95% CIs from 1000-sample nonparametric bootstrapping.
Results
A total of 23 452 eligible participants (mean [SD] age, 48.2 [11.1] years; 5790 [24.7%] female; mean [SD] HbA 1c , 6.9% [1.1%]) were cloned into 4 treatment strategies. Earlier ADM initiation compared with the control showed progressively lower point estimates for 3-point MACE (RR, 0.32; 95% CI, 0.15 to 1.11 for strategy 1; RR, 0.65; 95% CI, 0.41 to 1.29 for strategy 2; RR, 0.93; 95% CI, 0.70 to 1.41 for strategy 3), though it did not achieve statistical significance. Corresponding RDs were −0.97% (95% CI, −1.26% to 0.14%), −0.49% (−0.84% to 0.40%), and −0.10% (−0.44% to 0.57%), respectively. ADM initiation within 3 months yielded significant risk reduction for all-cause mortality compared with the control in both relative (RR, 0.31; 95% CI, 0.10-0.98) and absolute (RD, −0.40%; 95% CI, −0.57% to −0.01%) scales.
Conclusions and Relevance
In this cohort study, earlier ADM initiation following the diagnostic threshold for T2D showed a lower risk of mortality, suggesting a potential cardiovascular benefit of early glycemic control; however, given the low event counts and the observational nature of the study, further evaluation in larger studies is warranted before definitive conclusions can be drawn.