Derosa 2006a.

Methods	DURATION OF INTERVENTION: 12 months DURATION OF FOLLOW‐UP: 12 months RUN‐IN PERIOD: none LANGUAGE OF PUBLICATION: English
Participants	WHO PARTCIPATED: Caucasian patients with type 2 diabetes and poor glycaemic control with diet or experiencing adverse effects with diet and metformin, administered up to the maximum tolerated dose INCLUSION CRITERIA: patients aged >= 18 years of either sex if they had type 2 diabetes mellitus according to the ADA (duration >= 6 months), and if they had poor glycaemic control (HbA1c levels > 7.5%) or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose; all patients were diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III classification and they presented with triglyceridaemia (triglycerides >= 150 mg/dL) and hypertension according to WHO 1999 criteria (systolic/diastolic BP >= 130/ >= 85 mmHg); all patients had a fasting C‐peptide level > 1.0 ng/mL and were overweight (BMI 25.0 ‐ 28.1) EXCLUSION CRITERIA: history of ketoacidosis; unstable or rapidly progressive diabetic retinopathy, nephropathy, or neuropathy; impaired hepatic function (defined as plasma aminotransferase and/or gamma‐glutamyltransferase levels higher than the upper limit of normal (ULN) for age and sex], impaired renal function (defined as serum creatinine levels higher than the ULN for age and sex) or severe anaemia; patients with serious cardiovascular disease (e.g. NYHA class I–IV congestive heart failure or a history of myocardial infarction or stroke) or cerebrovascular conditions within 6 months before study enrollment; women who were pregnant, breastfeeding or of childbearing potential and not taking adequate contraceptive precautions DIAGNOSTIC CRITERIA: ADA 2001 CO‐MORBIDITIES: not stated CO‐MEDICATIONS: not stated
Interventions	NUMBER OF STUDY CENTRES: 3 COUNTRY/ LOCATION: Italy SETTING: Department of Internal Medicine and Therapeutics, University of Pavia (Pavia, Italy); the ‘G. Descovich’ Atherosclerosis Study Center, ‘D. Campanacci’ Clinical Medicine and Applied Biotechnology Department, University of Bologna (Bologna, Italy); the Diabetes Care Unit at S. Carlo Hospital of Milano (Milano, Italy). INTERVENTION (DOSE/DAY): metformin (mean dose 2250 mg/day) + rosiglitazone 4 mg/day (o.d., before lunch) CONTROL (DOSE/DAY): metformin (mean dose 2250 mg/day) + pioglitazone 15 mg/day (15 mg o.d., before lunch) TREATMENT BEFORE STUDY: diet or diet and metformin, administered up to the maximum tolerated dose TITRATION PERIOD: all paitents received metformin beginning with a dose of 1500 mg/day and increasing up to 3000 mg/day, self‐administered for 12 months, this dose depended on the tolerance or glycaemic control of the patients (mean dosage: 2250 ± 750 mg/day)
Outcomes	PRIMARY OUTCOMES: changes in BMI, HbA1c, lipid profile, lipoprotein variables SECONDARY OUTCOMES: (not stated) "FPG, PPG and HOMA index were also used to assess efficacy" BMI, HbA1c, fasting and postprandial plasma glucose (FPG, PPG) and insulin levels; HOMA; lipid profile; treatment tolerability
Notes	AIM OF STUDY: to assess the differential effect on glucose and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in patients with type 2 diabetes mellitus and metabolic syndrome.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate