Statins are among the most widely prescribed medicines worldwide, yet there is much to be understood about their benefits and harms. In a mini-symposium presented at the 82^nd Scientific Sessions of the American Diabetes Association (ADA), Dr Naveed Sattar from the University of Glasgow and Dr David Preiss from the University of Oxford discuss two contrasting aspects of statins in diabetes.

Statins in type 1 diabetes (Naveed Sattar, UK)

According to the QRISK3 risk prediction model, the cardiovascular disease (CVD) risk is 3-5 times higher in individuals with type 1 diabetes (T1D) compared with the general population. Similarly, the risk for heart failure with reduced ejection fraction is significantly higher among individuals with T1D compared with those with type 2 diabetes (T2D) and those without diabetes. Hyperglycemia is likely to be an independent factor driving the CVD risk in T1D.

Low-density lipoprotein cholesterol remains a key modifiable agent in the development of CVD in patients with T1D. Robust data from randomized controlled trials (RCTs) and observational studies have established that statins work well in reducing cardiovascular outcomes in patients with T1D.

In patients with T1D, the CVD risk rises sharply after the age of 40 years. One-fifth of them are likely to have CVD by the age of 50 years and a half by their mid-60s. Dr Sattar warrants initiating statin therapy in all patients aged >55 or 60 years of age, regardless of the risk factors. In patients younger than these ages, a risk score can be used to determine statin initiation; however, the risk scores may need to be recalibrated to each country's event rates.

Speculatively, initiating statins at a lower dose sooner may be more beneficial than starting at a higher dose later, but there is the pain of taking a tablet earlier in life. Statin intolerance is a concern, but the true rates remain low, and ezetimibe is a good alternative for those who cannot tolerate statins.

Statin use and new-onset diabetes (David Preiss, UK)

The JUPITER trial of rosuvastatin 20 mg vs placebo initially hypothesized that statin therapy may reduce new-onset diabetes. Rather, it found a 25% increase in physician-diagnosed diabetes. Later, when researchers conducted a meta-analysis of 15 RCTs of statins vs placebo, they found an 11% increase in the odds of new-onset T2D. Similarly, a meta-analysis of five trials of intensive- vs moderate-dose statins found a 12% increase in the odds of T2D.

The mechanism underlying the development of new-onset diabetes is poorly understood, but it appears to be an on-target effect of HMG-CoA reductase inhibition.

The Cholesterol Treatment Trialists (CTT) collaboration was initially set up in 1994 to study the effects of statins on major cardiovascular outcomes, mortality, and cancer. A new project was later initiated by CTT to investigate the potential harms associated with statin therapy. CTT is currently conducting analyses of 23 double-blind statin trials to understand the risk for new-onset diabetes and worsening diabetes.

ADA 2022 — Statins in diabetes: friend or foe?

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