Statins and diabetes — does cholesterol medication raise blood sugar?

Aim of the study: Meta-analyses of randomized control trials investigating the association between incident diabetes and statin use showed an increased risk of new-onset diabetes (NOD) from 9% to 13% associated with statins. However, short follow-up period, unpowered sample size, and lack of pre-specified diagnostic criteria for diabetes detection could be responsible of an underestimation of this risk.

Results: PubMed, EMBASE and MEDLINE databases were searched from inception to June 30, 2016 for cohort and case-control studies with risk of NOD in users vs nonusers, on ≥1000 subjects followed-up for ≥1 year. Two review authors assessed study eligibility and risk of bias and undertook data extraction independently. Pooled estimates were calculated by a random-effects model and between-study heterogeneity was tested and measured by I2 index. Furthermore, stratified analyses and the evaluation of publication bias were performed. Finally, the meta-analysis included 20 studies, 18 cohort and 2 case-control studies. Overall, NOD risk was higher in statin users than nonusers (RR 1.44; 95% CI 1.31-1.58). High between-study heterogeneity (I2 = 97%) was found. Estimates for all single statins showed a class effect, from rosuvastatin (RR 1.61; 1.30-1.98) to simvastatin (RR 1.38; 1.19-1.61). The present meta-analysis confirms and reinforces the evidence of a diabetogenic effect by statins utilization.

Aim of the study: Randomized trials suggest moderate-intensity statins increase type 2 diabetes risk by around 11% with a potential further 12% moving to high-intensity statins, such that high intensity may increase risk by 20% or more relative to placebo. These data translate into one extra diabetes case per 100-200 statin recipients over 5 years, with ∼10-fold greater benefits on major vascular outcomes.

Results: The underlying mechanisms for diabetes harm are not clear but could include modest weight gain (noted in randomized trials), or, speculatively, beta cell harm. Concordant genetic studies link HMG CoA Reductase inhibition to diabetes risk and weight gain. Patients should be warned about a slight diabetes risk when prescribed statin and told that modest lifestyle improvements can i) nullify diabetes risk, and ii) improve cardiovascular risks beyond statins. Doctors should also measure glycemia status post statin commencement, most commonly with HbA1c, and tailor lifestyle advice and care dependent on the results.

Aim of the study: Atherosclerotic cardiovascular disease (ASCVD) and diabetes are leading causes of morbidity and mortality in the United States and globally. Statin medications, a cornerstone of ASCVD prevention and treatment strategies, have been demonstrated to cause hyperglycemia and new onset diabetes mellitus (NODM).

Results: Since initial reporting of statin-induced hyperglycemia and NODM, the totality of available data corroborates an association between incident diabetes and statin use. A consensus that high-intensity statin and individuals with obesity or glycemic parameters approximating diabetes thresholds constitute the majority of risk exists. Alterations in insulin signaling, glucose transport and gastrointestinal microbiota are leading hypotheses underlying the mechanisms of statin-induced hyperglycemia. The probability of NODM based on an individual's risk factors and statin specific properties can be anticipated. This risk needs to be contextualized with the risk of ASCVD. In order to effectively adjudicate the risk of NODM, improvement in formulating and ultimately conveying a comprehensive ASCVD risk assessment to patients is necessary.

Aim of the study: Statins are widely used to prevent cardiovascular disease events. Cardiovascular diseases and type 2 diabetes are tightly connected since type 2 diabetes is a major risk factor for cardiovascular diseases.

Results: However, they have also important side effects, including an increased risk of type 2 diabetes. The first study reporting an association of statin treatment with the risk of type 2 diabetes was the WOSCOPS trial (West of Scotland Coronary Prevention Study) in 2001. Other primary and secondary cardiovascular disease prevention studies as well as population-based studies have confirmed original findings. The purpose of our review is to examine and summarize the most important findings of these studies as well as to describe the mechanisms how statins increase the risk of type 2 diabetes.

Aim of the study: In randomized trials and many observational studies, statins are associated with a modest excess of type 2 diabetes mellitus. High-intensity statins, such as atorvastatin 80 mg and rosuvastatin 20 mg, are associated with a higher excess risk of diabetes than moderate-intensity statins, such as atorvastatin 10 mg, simvastatin 20-40 mg, or pravastatin 40 mg.

Results: Multiple mechanisms have been proposed for statin-associated diabetes risk, primarily related to increased insulin resistance or impaired insulin secretion. Genetic polymorphisms with reduced HMG CoA reductase function are associated with weight gain, insulin resistance, and diabetes. Animal models have shown that HMG CoA inhibition has multiple downstream effects that may increase diabetes risk. Statin impairment of insulin signaling, decreased adipocyte differentiation, decreased pancreatic β-cell insulin secretion, and other effects have also been found. The excess risk of diabetes appears to be confined to those who are already at risk for developing diabetes. Diabetes is diagnosed only 2-4 months earlier in statin-treated patients and therefore is unlikely to have no long-term adverse consequences.

Aim of the study: Statins are the most commonly prescribed cholesterol-lowering drugs for cardiovascular prevention. Data from randomized clinical trials have shown an increased risk of diabetes mellitus type 2 (DT2) on statin treatment.

Results: The molecular mechanisms remain partly unknown. The risk of TD2 is higher with high doses of statins and in people with preexisting risk factors for T2D (prediabetes, metabolic syndrome). The cardiovascular benefit of statins overdrive by far the risk of diabetes and the prescription of statins in high risk cardiovascular subjects should not be questioned. Glycaemic monitoring and the adaptation of lifestyle and dietary measures are recommended for subjects at risk of T2D.