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<h4>Aims</h4>People with Type 2 diabetes experience higher cardiometabolic risk, and both synthetic glucocorticoids and use of 5α-reductase inhibitors have been individually linked to increased risk of myocardial infarction. We tested whether the increase in risk is exacerbated by co-prescription of both drugs.<h4>Materials and methods</h4>We performed a population-based cohort study in the Scottish Diabetes Research Network-National Diabetes Dataset (SDRN-NDS) and IQVIA Medical Research Data-UK (IMRD-UK). Patients with Type 2 diabetes aged ≥ 40 years receiving 5α-reductase inhibitors or tamsulosin, who were incident users of systemic glucocorticoids during 2006-2021 were included. We modelled the joint effect of 5α-reductase inhibitors and cumulative exposure to glucocorticoids on the risk of myocardial infarction using a time-varying Cox proportional hazards model.<h4>Results</h4>A total of 13 161 patients with Type 2 diabetes were included in SDRN-NDS and 15 084 in IMRD-UK. Mean age was 71.4 ± 9.6 and 72.3 ± 9.4 years, with mean follow-up of 4.7 (3.6) and 5.6 (4.0) years, respectively. Median (IQR) total glucocorticoids exposure was 210 (96-630) and 420 (200-1240) prednisolone-equivalent milligram. Risk for myocardial infarction was increased among users of 5α-reductase inhibitors (HR [95% CI]: SDRN-NDS, 1.21 [1.02-1.43]; IMRD-UK, 1.27 [1.02-1.59]) and per SD increase in cumulative glucocorticoid exposure (HR [95% CI]: SDRN-NDS, 1.09 [1.03-1.14]; IMRD-UK, 1.08 [1.01-1.15]). We did not observe a multiplicative interaction (SDRN-NDS, p = 0.44; IMRD-UK, p = 0.68) between the use of the two drugs.<h4>Conclusion</h4>People with Type 2 diabetes exposed to 5α-reductase inhibitors or glucocorticoids are at an increased risk of myocardial infarction, although a multiplicative interaction between the use of the two drugs was not found.

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