(2016) of primary prevention RCTs reporting statin-induced adverse events, there was no increased risk for new-onset DM in patients treated with moderate-dose statins versus placebo (relative risk [RR]: 1.05, 95% CI: 0.91 1.2).[37] However, the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study, used a high-dose statin for primary prevention and reported a higher risk for DM than placebo (RR: Another systematic review by Engeda et al. (2019) of statins for primary prevention demonstrated a borderline significant increase in DM risk in 78,039 patients from RCTs (RR: 1.11, 95% CI: 1.00 1.22) and a significant increase in DM incidence in nearly four million patients from observational studies (RR: 1.55, 95% CI: 1.39 1.74).[48] A systematic review by Macedo et al. (2014) of 90 observational studies of all statin doses for primary and secondary prevention showed a trend towards an increased risk for DM that did not reach significance (odds ratio [OR]: 1.31, 95% CI: 0.99 1.73).[49] While statins may increase the risk of DM, the risk has not been demonstrated in RCTs of moderate-dose statins. Observational studies suggest a low risk of DM attributable to moderate-dose statins. Other adverse effects of statins reported in clinical trials may include muscle-related complaints and elevation of liver transaminases. However, in the Chou et al. (2016) systematic review of primary prevention trials, there was no increase in serious adverse events, cancer or fatal cancer, myalgias or elevation of liver transaminases, or the risk for withdrawal because of adverse events.[37] Although there was no increased risk for rhabdomyolysis or myopathy, some trials reported these adverse events. This meta-analysis included all statin doses.[37] Macedo et al. 