Statins and Diabetes: The Plot Thickens

Abstract

S tatins have now been used in clinical practice for more than 20 years, and are the cornerstone of primary and secondary prevention of cardiovascular disease. The increased risk of new-onset type 2 diabetes in patients treated with statins has been well established by large meta-analyses of randomized controlled trials and observational studies. 1,2 In a meta-analysis of 13 statin intervention trials involving 91,140 participants, statin therapy was associated with a 9 % increased risk of incident diabetes; treatment of 255 patients with statins for 4 years resulted in one extra case of diabetes, while 5.4 cases of death or myocardial infarct were prevented. 1 Similar results were obtained from another meta-analysis comparing intensive-dose with moderate-dose statin therapy among 32,752 participants without diabetes; 2.0 additional cases of diabetes in the statin-intensive group were observed per 1000 patient-years, but with 6.5 fewer instances of cardiovascular events. 3 Recent data from the higher-risk population cohort in the Metabolic Syndrome in Men (METSIM) study, however, which included 8749 non-diabetic participants aged 45 to 73 years who were followed for 5.9 years, indicated a 56 % increased risk (11.2 versus 5.8 %) in statin-treated patients, which was dose-dependent for simvastatin and atorvastatin, suggesting that statin treatment may be associated with a much higher risk of diabetes in a population with a high risk of diabetes at baseline. 4 Even in patients with type 2 diabetes, statin treatment is associated with worsening glycemic control. In pooled analyses of nine trials involving 9696 patients over a follow-up period of 3.6 years, mean HbA1c levels increased by 0.2 % in patients randomized to statin versus control treatment. 5 This dysglycemic effect of statins is apparently due to a reduction in both insulin sensitivity and secretion. 4 In addition, variants in the gene encoding HMG-CoA reductase, the target of statins, are associated with higher body weight, waist circumference, plasma glucose, and insulin concentrations, suggesting that the increased risk of type 2 diabetes due to statins may be partially explained by HMG-CoA reductase inhibition. 6 Furthermore, studies have suggested that statin treatment is related to impaired exercise training and decreased diet compliance. 7 A new dimension in this saga is suggested in this issue of JGIM by Mansi et al., who report that statin use may be associated with diabetic complications in a retrospective cohort study of adult patients enrolled in the US military's Tricare program in San Antonio, TX. 8 The authors selected patients without cardiovascular problems or significant comorbid conditions and, using propensity scores to match the two groups, selected 3351 statin users and 3351 non-users. After follow-up of 6.5 years, the authors observed that statin users had an odds ratio (OR) of 1.87 for diabetes (30.9 % versus 19.4 %), 2.5 for diabetic complications (5.0 % versus 2.1 %), and 1.14 for overweight/obesity (46.7 % versus 43.4 %) compare...

Selected 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors. A look into their use and potential in pre-diabetes and type 2 diabetes

“…Words of caution are in order in that, controversially (Mogadam 2014;Skoumas et al 2018), some of the statins have been suggested in some papers increase the incidence of T2D in patients at risk of that pathology (Macedo et al 2014;Gastaldi and Philippe 2015;Climent et al 2017;Li et al 2018). Indeed, Barkas et al (2020) noted that the greatest risk of statin-caused T2D is in the metabolically unhealthy obese and metabolically unhealthy nonobese patients with statin treated metabolically healthy obese not being at risk of T2D; however, the metabolically healthy obese can, in a non-statin related manner become metabolically unhealthy (Kouvari et al 2019), and so caution with statin use must be exhibited in those moving toward a metabolically unhealthy state even though such is not statin-related.…”