RESEARCH 2017.

Methods	Design: randomised, open‐label, prospective study Number of study centres: multi‐centres (10) in Japan Setting: outpatient Patient recruitment: not reported Duration of study (Follow‐up): 52 weeks Clinical setting: T2DM patients with hypercholesterolaemia
Participants	Enrolment (N): 109 Randomised (N): intervention:53 ; control:56 Withdrawn (N): not reported Lost to follow‐up (N): not reported Completed the study (N): intervention: 51; control:53 Analysed (N): intervention: 53; control:56 Age (years) (mean ± SD): intervention: 61.7 ± 11.1; control: 62.6 ± 9.5 Sex (male, N, %): intervention:31 (58.5%); control: 32 (57.1%) Smoking history (N, %): intervention: 13 (24.5%); control:13 (23.6%) BMI (kg/m², mean ± SD):): not reported Diabetes (N, %): intervention:51 (100%) ; control:53 (100%) Hypertension (N, %): not reported History of CHD (N, %): intervention: 8 (15.1%); control:6 (10.7%) Statin pretreatment (N, %): intervention:53 (100%) ; control:56 (100%) Inclusion criteria: the type 2 diabetic outpatients were over 20 years of age and had failed to reach the target LDL‐C values recommended by the guideline (LDL‐C < 120 mg/dL for patients with no history of CAD; LDL‐C < 100 mg/dL for patients with a history of CAD) after receiving high‐potency statins (10 mg of atorvastatin or 1 mg of pitavastatin) for more than 1 month. Exclusion criteria: (1) history of hypersensitivity to atorvastatin, pitavastatin or ezetimibe; (2) serum triglyceride level more than 400 mg/dL; (3) hepatic dysfunction (an ALT level that is more than twice the upper limit of the normal range); (4) uncontrolled diabetes (HbA1c more than 9.0%); (5) renal dysfunction (a creatinine level that is higher than 2.0 mg per dL); (6) secondary or drug‐induced hypercholesterolaemia; (7) homozygous familial hypercholesterolaemia; (8) pregnant or nursing women or women suspect of pregnancy; (9) judged as inappropriate for study by doctor.
Interventions	Intervention: ezetimibe 10 mg/day + (atorvastatin 10 mg/day or pitavastatin 1 mg/day). Comparison: atorvastatin 20 mg/day or pitavastatin 2 mg/day Details of any 'run‐in' period: not reported Concomitant medications: not reported Excluded medications: statins other than atorvastatin or pitavastatin, anion‐exchanging resin agents, fibrates, nicotinic acids, eicosapentaenoic acid, probucol, or other lipid‐lowering agents.
Outcomes	Primary: the per cent change in LDL‐C from baseline. Secondary: the rates at which the target LDL‐C values recommended by the guidelines were achieved and the values and per cent changes in total cholesterol (TC), triglyceride (TG), HDL‐C, high‐sensitivity CRP (Hs‐CRP), sd‐LDL, and remnant‐like particle cholesterol (RLP‐C). Other: general parameters such as AST, ALT, creatinine, and creatine phosphokinase (CPK), along with plasma glucose, HbA1c values and serum insulin level. Adverse events.
Notes	Funding: This study was supported by research grants from Japan Vascular Disease Research Foundation. UMIN000002593
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was performed with stratification according to age and gender. When a patient was enrolled, a doctor placed an order for random assignment by entering the data (including age and year) into the randomization software installed at the monitoring office of Nouvelle Plus."
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not reported
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	An intention‐to‐treat analysis and per protocol analysis were performed.
Selective reporting (reporting bias)	Low risk	No protocol published, but a pre‐registration in a clinical trial registry was found (UMIN000002593). All prespecified outcomes were reported.
Other bias	Low risk	Quote: "Funding: This study was supported by research grants from Japan Vascular Disease Research Foundation." Quote: "Teruo Shiba has received honoraria from Shionogi & Co., Ltd., Pfizer Japan Inc., Merck Sharp & Dohme (MSD), Kowa Company, Ltd., and Daiichi Sankyo Company Limited. Tsutomu Yamazaki has received research support and honoraria from Merck Sharp & Dohme (MSD), Pfizer Japan Inc., Kowa Company, Ltd., Shionogi & Co., Ltd., and AstraZeneca K.K., and honoraria from Bayer Holding Ltd. and Daiichi Sankyo Company Limited. Akira Tanaka has received research support from Daiichi Sankyo Company Limited and honoraria from Merck Sharp & Dohme (MSD), and Kewpie Corporation. Takahide Kohro has received research support from AstraZeneca K.K. and honoraria from Merck Sharp & Dohme (MSD). The other authors have no conflicts of interest to declare."