Statin use in patients with diabetes: one drug, multiple benefits

Khalil et al. [1] discuss the use of statins in patients with diabetes mellitus (DM), concluding that statin therapy is recommended for DM patients, 40 to 75 years old, with low-density lipoprotein cholesterol (LDL-C) levels >70 mg/dl or Atherosclerotic Cardiovascular Disease (ASCVD) risk score ≥7.5%. However, it should be noted that the current (2019) American Diabetes Association (ADA) guidelines recommend that DM patients aged <40 years should take a high-intensity statin, if they have ASCVD or 10-year ASCVD risk >20% [2]. Furthermore, in these patients, a moderate-intensity statin may be initiated in the presence of ASCVD risk factors, including LDL-C ≥ 100 mg/dl, smoking, hypertension, albuminuria, chronic kidney disease (CKD) and family history of premature ASCVD [2]. The same guidelines mention that DM patients ≥40 years should take a moderate-intensity statin, irrespective of other comorbidities; high-intensity statin therapy may be considered, in the presence of the abovementioned ASCVD risk factors [2]. If these patients have a history of ASCVD or 10-year ASCVD risk >20%, a high-intensity statin should be administered.

Apart from LDL-C risk reduction, statins may exert further benefits in DM patients [3]. In this context, it has been shown that statins can improve urinary albumin excretion rates and albuminuria, especially in type 2 DM patients with diabetic nephropathy [4]. Statins may also minimize the risk for contrast-induced acute kidney injury (CI-AKI) in DM patients [5]. CI-AKI has been associated with increased CVD and renal morbidity, as well as all-cause death and prolonged hospitalization [6]. Hyperuricemia has been linked to micro- and macro-vascular diabetic complications [7]. Statins may decrease serum uric acid levels [8].

Non-alcoholic fatty liver disease (NAFLD) frequently co-exists with type 2 DM; these two metabolic disorders share common pathophysiological mechanisms [9]. Statins have been reported to improve both the biochemical and histological features of NAFLD and its advanced form, i.e. non-alcoholic steatohepatitis (NASH) [10]. Interestingly, apart from NAFLD, other abnormal peri- or intra-organ fat depots (APIFat), including epicardial, perirenal, pancreatic, intramuscular and perivascular adiposities, may further increase ASCVD risk [11].

The additional benefits of statins in patients with type 2 DM mentioned above, highlight the clinical importance of statin therapy. There is strong evidence that lower is better for LDL-C levels in terms of CVD risk reduction. But there is also evidence that lower LDL-C levels for longer is better [12]. These data should influence the decision to initiate early statin treatment in DM patients. In this context, current ADA guidelines support statin use in DM patients even <40 years in the presence of ASCVD, 10-year ASCVD risk >20% or ASCVD risk factors [2]. It should be emphasized that, although statins have been linked to new-onset DM, the risk-benefit ratio strongly favours statin therapy in patients at high ASCVD risk [13].

Should we reconsider/revise the guidelines at some stage to include more patients with T2DM who should be started earlier on a statin? Is it a time for more individualisation of treatment? We would appreciate the expert opinion of Khalil et al. [1] on this controversial issue.

Declaration of interest

NK has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, Astra Zeneca, Boehringer Ingelheim, Mylan, Novo Nordisk, Sanofi and Servier. KK has given talks, attended conferences and participated in trials sponsored by Amgen, Astra Zeneca, Boehringer Ingelheim, MSD, Pharmaserv Lilly, Novo Nordisk, Sanofi and Servier. VGA has nothing to declare. DPM has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec.