Statin use and risk for type 2 diabetes: what clinicians should know

Abstract

Statins are the first line of pharmacologic treatment for the management of hypercholesterolemia in patients at risk for atherosclerotic cardiovascular (CV) disease. In recent years, several randomized, controlled trials (RCTs) and observational studies have reported increased risk for new-onset type 2 diabetes mellitus (T2D) with statin treatment, particularly with use of high-intensity statins that reduce low-density lipoprotein cholesterol (LDL-C) by 50% or more. This paper summarizes the data from RCTs and observational studies for statin-associated T2D risk, and puts into perspective this evidence, weighed against the established benefits of statin therapy for CV risk reduction. In RCTs, the increase in T2D risk with statin therapy appears to be attributable mainly to those with major T2D risk factors. The increase in incidence of T2D in those with major risk is approximately 25% for statin use, compared to placebo, and for intensive statin therapy compared to moderate-intensity statin therapy. However, in those with major T2D risk factors, the number of CV disease events prevented for each excess case of T2D is close to or greater than one, indicating that the risk-benefit ratio still strongly favors use of statin therapy, or intensive statin therapy, for patients with sufficient CV disease risk to warrant cholesterol-lowering drug therapy. Recommendations are summarized for evaluation of the T2D risk factor profile before initiation of and during statin therapy. In addition, the importance of lifestyle management and other preventive measures is emphasized for management of risks for both T2D and CV disease events in patients receiving statin therapy.

Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights

“…Although the principal mechanism of the action of statins is inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme-A (HMG-CoA) reductase, statins have been implicated in several other beneficial pleiotropic effects including improving endothelial function, stabilization of atherosclerotic plaques and anti-inflammatory activities [3]. Despite the safety and relative tolerability of statins, observational studies [4][5][6][7][8], clinical trials [9,10] and meta-analyses [11][12][13][14][15][16] have found that statins can increase the risk of new-onset type 2 diabetes mellitus (T2DM). These studies implicated statins in negatively impacting insulin sensitivity, decreasing secretion by pancreatic β-cells and increasing insulin resistance [11,17,18].…”

How do we know that statins are diabetogenic, and why? Is it an important issue in the clinical practice?

“…Before initiation of statin therapy the risk of diabetes should be assessed [1,36,37]. Statin-treated patients at high risk of developing diabetes should be monitored for changes in blood glucose and HbA1c levels, and preventive lifestyle modification should be introduced.…”

“…Observational studies [1][2][3][4][5][6], controlled clinical trials [7,8], and meta-analyses [9][10][11][12][13][14] indicate that statins induce diabetes, and intensive statin therapy is more diabetogenic than moderate-intensity therapy [15,16]. This issue has been of interest only since 2008, when a primary prevention trial with rosuvastatin was published, showing a 44% reduction in the rate of cardiovascular events versus placebo (relative risk [RR] 0.56; 95% confidence interval [CI] 0.46-0.69) but also a 25% higher risk of diabetes (RR 1.25; 95% CI 1.05-1.49) [7].…”

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

“…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].…”