Study design Study sample Samples with DM no./total no. (%) Statin Dose and duration Recruitment time Assessment of clinical response References In vivo Nondiabetic and diabetic patients 20 nondiabetic and 32 diabetic renal transplant recipients Atorvastatin acid — — ↓ clearance and ↑ plasma concentration of atorvastatin lactone as atorvastatin acid metabolite (M. Dostalek et al., 2012) In vitro Human liver microsomal fractions obtained from 12 nondiabetic and 12 diabetic donors Prospective study ACS patients with diabetes 126 ACS patients with DM ( Atorvastatin — 9–12 months A considerable correlation between [16 ] Animal study Male Wistar diabetic rats (50 mg/kg STZ, i.p.) Atorvastatin-treated diabetic ( Atorvastatin 10 mg/kg, orally Days 29-35 after diabetes induction ↓ serum atorvastatin concentration (H. [17 ]) Atorvastatin-treated nondiabetic ( Animal study Male Wistar diabetic rats (50 mg/kg STZ, i.p.) Nontreated diabetic ( Atorvastatin 10 mg/kg, orally Two weeks ↓ CYP3A2 mRNA expression (Hassan [18 ]) Atorvastatin-treated nondiabetic ( Animal study Male Wistar diabetic rats (35 mg/kg STZ, i.p.) Atorvastatin 10 mg/kg: oral Single dose ↑ atorvastatin clearances after both oral and intravenous treatments [19 , 20 ] Cellular study Primary hepatocytes of diabetic rats 0.1, 0.5, 2, 10, 40, and 100 μ M Animal study Male Wistar diabetic rats (40 mg/kg STZ, i.p.), nondiabetic rats Acute atorvastatin study plus IPost Atorvastatin 50 μ mol/L During reperfusion (120 min) Limitation of infarct size and retrieval of contractile dysfunction in two nondiabetic and diabetic groups [21 ] Chronic atorvastatin study plus IPost 10 mg/kg daily for plus IPost 2 weeks eNOS phosphorylation Animal study Male Wistar diabetic rats (40 mg/kg STZ, i.p.), nondiabetic rats Atorvastatin 10 mg/kg 24 hr Improvement in CD44 and caspase-3 expression and oxidative stress and kidney function biomarkers in both groups [22 ] Animal study Injection of low-dose STZ and HFD to male Sprague-Dawley rats Atorvastatin A single 10 mg/day No ↑ hepatic CYP3a and OATP1b2 expression [23 ] Animal and cellular study Diabetic rats induced by STZ (35 mg/kg) and HFD Atorvastatin 10 mg/kg, 20 mg/kg, and 40 mg/kg 10 days 10 mg/kg and 20 mg/kg of atorvastatin caused severe hepatotoxicity [19 , 20 ] HepG2 cells 2, 10, and 30 μ M Case-control study Hyperlipidemic HD Caucasian patients 10/14 Simvastatin A single 10 mg/day 6 months More lowered anti-inflammatory effects in nondiabetic patients [24 ] Case-control study Diabetic patients with low-density lipoprotein cholesterol: 50 to 125 mg/dL 4933 (27%) patients with DM Placebo/simvastatin 40 mg 7 years ↓ low-density lipoprotein cholesterol in diabetic patients [25 ] Retrospective propensity score-matched cohort study Patients with or without diabetes 545 diabetic and 1292 nondiabetic Simvastatin 20 mg/kg From January 2005 to June 2015 ↑ the incidence rate of mortality in diabetic patients [26 ] Animal study Male Wistar diabetic rats (35 mg/kg, i.p.) Simvastatin 20 mg/kg, p.o. Single dose ↓ simvastatin and simvastatin acid AUC [27 ] Cellular study Primary hepatocytes of diabetic rats Prospective study Patients who had undergone PCI 202 diabetic (120 on fluvastatin, 82 placebos) Fluvastatin 40 mg twice daily 3 to 4 years ↓ MACE risk in diabetic patients [28 ] 1475 nondiabetic (724 on fluvastatin, 751 on placebo) Animal study Male Wistar diabetic rats (50 mg/kg STZ, i.p.) and nondiabetic rats Fluvastatin 5 mg/kg 24 hr Alteration in pharmacokinetics of fluvastatin because of diabetes in a stereoselective manner [29 ] Animal study Male Wistar diabetic rats (50 mg/kg STZ, i.p.) Pravastatin 5 mg/kg i.v. — ↑ expression of oatp2 [30 ] Animal study Male Wistar diabetic rats (35 mg/kg, b.w., i.p.) Pravastatin 10 mg/day 28 days ↑ serum pravastatin concentration [31 ] Prospective study Consecutive AMI patients (diabetic or nondiabetic) underwent PCI 802 patients Pitavastatin 2 mg/day 12 months Diabetes was recognized as an independent predictor of TVR-MACE [32 ] Prospective study Elderly patients with or without type 2 diabetes and hypertension 80 patients Pitavastatin simvastatin Pitavastatin: 1-2 mg/d 2, 4, 8 weeks Alike decrement in blood lipid and liver dysfunction in both groups [33 ] Prospective study Chinese diabetic and nondiabetic patients with acute ischemic stroke history It varies based on the types of models in the study Any type of statins Any dosages of statins 3 months, 1 year No relationship between statin therapy and stroke recurrence in patients with diabetes [34 ] Prospective study Diabetic and nondiabetic patients affected coronary artery disease who undergone serial optical coherence tomography imaging 54 plaques in 41 diabetic patients and 63 plaques in 49 nondiabetic patients Any type of statins Any dosages of statins 1 year ↑ minimum FCT in both groups [35 ] Retrospective cohort study Patients with and without diabetes aged 75 years or more without a history of atherosclerotic CVD and statin use or they were statin new users 46864 people aged 75 years or more Any type of statins Any dosages of statins 2006-15 In nondiabetic patients: ↑ atherosclerotic CVD incidence until more than the proposed risk thresholds for statin treatment [36 ]
