Type-2 diabetes mellitus (T2DM) is an increasingly epidemic disease, with the prevalence projected to reach 366 million worldwide by 2030, according to the World Health Organization. It has long-term macrovascular complications, including cardiovascular disease (CVD).

Kelly et al. conducted a meta-analysis of five large randomized, controlled trials with a combined total of 27,802 patients, which compared intensive glucose control to conventional treatment of T2DM. The endpoints of interest included CVD and mortality. The authors concluded that intensive glucose control did reduce the risk of CVD, but did not decrease the incidence of CVD mortality and had the side-effect of an increased risk of hypoglycaemic episodes. Additionally, it was noted that the use of the thiazolidinedione, rosiglitazone may increase the risk of myocardial infarction.

The individual trials produced conflicting results that can, at least partly, be explained by the varying definitions of conventional and intensive therapy between the studies. The United Kingdom Prospective Diabetes Study (UKPDS) used an oral hypoglycaemic agent or insulin as intensive therapy and dietary adjustment as conventional therapy. However, the other trials gave their conventionally treated patients some limited pharmacological therapy. The UKPDS trial found a reduced risk of CVD mortality in the intensively controlled patients, but the other studies did not. This suggests that some, but not intensive, pharmacological therapy is required to reduce the risk of CVD mortality in T2DM patients.

The reduced risk of CVD mortality does appear to be directly related to glycaemic control since the median percentage HbA_1c of the ‘intensively’ controlled patients in the UKPDS trial was similar to those treated ‘conventionally’ in the more recent trials. In conclusion, good glycaemic control is required to reduce the risk of CVD mortality in T2DM patients. However, overly intensive therapy does not reduce mortality and carries a significant risk of severe hypoglycaemia.