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BACKGROUND	Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration .
BACKGROUND	We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes .
METHODS	We did a single-centre , double-blind , placebo-controlled trial at the Glasgow Clinical Research Facility ( Glasgow , UK ) .
METHODS	We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences .
METHODS	Participants were randomly assigned ( 1:1 ) by computer to either metformin ( 850 mg twice daily ) or matching placebo in block sizes of four .
METHODS	Patients , investigators , trial staff , and statisticians were masked to treatment allocation .
METHODS	The primary endpoint was progression of mean distal carotid intima-media thickness ( cIMT ) over 18 months in the modified intention-to-treat population .
METHODS	Secondary endpoints were changes in carotid plaque score ( in six regions ) , measures of glycaemia ( HbA1c , fasting glucose , and insulin concentrations , and Homeostasis Model Assessment of Insulin Resistance [ HOMA-IR ] ) , and concentrations of lipids , high sensitivity C-reactive protein , and tissue plasminogen activator .
METHODS	The trial was registered at ClinicalTrials.gov , number NCT00723307 .
RESULTS	We screened 356 patients , of whom we enrolled 173 ( 86 in the metformin group , 87 in the placebo group ) .
RESULTS	Average age was 63 years .
RESULTS	At baseline , mean cIMT was 0717 mm ( SD 0129 ) and mean carotid plaque score was 243 ( SD 155 ) .
RESULTS	cIMT progression did not differ significantly between groups ( slope difference 0007 mm per year , 95 % CI -0006 to 0020 ; p = 029 ) .
RESULTS	Change of carotid plaque score did not differ significantly between groups ( 001 per year , 95 % CI -023 to 026 ; p = 092 ) .
RESULTS	Patients taking metformin had lower HbA1c , insulin , HOMA-IR , and tissue plasminogen activator compared with those taking placebo , but there were no significant differences for total cholesterol , HDL-cholesterol , non-HDL-cholesterol , triglycerides , high sensitivity C-reactive protein , or fasting glucose .
RESULTS	138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group .
RESULTS	Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group ( 28 vs 5 ) .
CONCLUSIONS	Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk , taking statins .
CONCLUSIONS	Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population .
BACKGROUND	Chief Scientist Office ( Scotland ) .

