Statin use in patients with diabetes amid COVID-19 pandemic

Dear Sir,

We read the meticulously performed CORONADO study by Cariou et al. [1] published in the journal with interest and concern. The study [1] specifically assessed the association between routine use of statin and coronavirus disease 2019 (COVID-19)-related outcomes among inpatients with type 2 diabetes. The authors reported that routine statin treatment was significantly associated with increased odds of 7-day mortality (odds ratio (OR) 1.74 {95% confidence interval 1.13–2.65]) and 28 days (OR 1.46 [1.08–1.95]) and 28-day mortality in patients with type 2 diabetes hospitalised for COVID-19, even after adjustment of several covariates. The findings are in contradiction with those reported in the systematic review and meta-analysis [2,3] of observational studies, which demonstrated that routine use of statins was associated with a significantly lower risks of all-cause mortality (hazard ratio (HR) 0.70 [0.58–0.84], n = 21,127, and OR 0.63 [0.51–0.79], n = 115,097) and the composite endpoint of severe illness (OR 0.80 [0.73–0.88, n = 10,081) in patients with COVID-19, compared to non-use of statins.

Some researchers [4] may dismiss the reported association as outlier findings. However, we believe that the findings should not be dismissed easily until proven otherwise. A recent study [5] which included 83,022 propensity-scored matched pairs of statin users and non-users and investigated diabetes progression after initiation of statin use in patients with diabetes, reported that the risk of diabetes progression composite outcome, which was comprised of new insulin initiation, increased in the number of glucose-lowering medication classes, the incidence of 5 or more measurements of blood glucose of ≥ 200 mg/dL, or a new diagnosis of ketoacidosis or uncontrolled diabetes, was significantly higher among patients with diabetes who were statin users compared to non-users. Therefore, the potentially worse glycaemic control among patients with type 2 diabetes who receive long-term statins compared to those who do not receive long-term statin may predispose them to unfavourable prognosis after the acquisition of COVID-19, since uncontrolled diabetes itself (and insulin use) has been an independent risk factor of mortality in patients with COVID-19. In fact, in the study by Cariou et al. [1], there was a significantly higher rate of routine insulin use in statin users than non-users.

Certainly, we believe that the association between routine use of statin and unfavourable prognosis among patients with type 2 diabetes is worthy of more investigations to confirm its existence, preferably in larger prospective studies. Furthermore, if the association is proven to be likely, we might need to re-examine the risk-benefit of statin use in patients with diabetes amid the COVID-19 pandemic. In the meantime, the necessity to adhere to a strict lifestyle routine should be highlighted in order to retard the worsening of glycaemic control among statin users with diabetes.