Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide

Cardiovascular mortality and morbidity are increased in patients with type 2 diabetes. However, there are few data from clinical trials comparing cardiovascular effects of alternative oral anti-diabetic agents. Major cardiovascular outcomes during four one-year, double-blind trials in over 3700 patients with type 2 diabetes randomised to either a thiazolidinedione, pioglitazone, metformin or a sulphonylurea, gliclazide treatment have been combined. Mean blood pressure was slightly reduced by all treatments, with pioglitazone treatment resulting in the largest falls (approximately 1.5 mmHg). Hospitalisations for cardiac or cerebrovascular events were similar with the different treatments. Overall mortality was seven of 1857 for pioglitazone and 10 of 1856 for non-pioglitazone treatments, of which three and six were cardiac deaths, respectively. The incidence of congestive cardiac failure was similar with pioglitazone (12/1857) and non-pioglitazone (10/1856) treatments. The results show similar cardiovascular outcome for the three different treatments over a one-year period, but demonstrate interesting differences, which will require longer-term formal outcome studies to determine their significance.