PROactive

Methods	A multicentre, randomised, double‐blind, placebo‐controlled trial
Participants	People aged 35 to 75 years with type 2 diabetes and a previous stroke (6 months before randomisation) were included. 984 eligible people were randomised into the trial, with 486 in the pioglitazone group and 498 in the placebo group.
Interventions	Pioglitazone titration from 15 mg to 45 mg per day depending on tolerability or placebo was given until the first occurrence of any of the events described in the primary outcomes. The mean duration was 34.5 months.
Outcomes	Primary outcomes: all‐cause mortality, non‐fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, cardiac intervention (including coronary artery bypass graft surgery or percutaneous coronary intervention), leg revascularisation, and amputation above the ankle Secondary outcomes: all‐cause death, non‐fatal myocardial infarction or non‐fatal stroke; adverse events
Notes	We did not include data for participants without previous stroke.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of random sequence generation was not described.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not reported.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to judge
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to judge
Incomplete outcome data (attrition bias) All outcomes	High risk	882/984 (90%) participants completed the final visit: 439/486 (90%) in the pioglitazone group and 443/498 (89%) in the placebo group. Intention‐to‐treat analysis was used.
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported.
Other bias	Unclear risk	This study was funded by Takeda Pharmaceuticals and Eli Lilly, and designed by the international steering committee, who also approved the protocol and amendments. The sponsors had 2 representatives on the international steering committee; the same 2 were also members of the executive committee. Data analysis, data interpretation, and writing of the report was done by the executive committee, with contributions from the international steering committee, the data and safety monitoring committee, and the endpoint adjudication committee. All the authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

TIA: transient ischaemic attack