Patients with type 2 diabetes mellitus (T2D) have an elevated mortality and morbidity compared to the general population. T2D is characterised by several metabolic defects that include impaired insulin secretion and action causing chronic hyperglycaemia (high glucose levels in the blood). Chronic hyperglycaemia is strongly associated with increased risk of kidney, eye, and nerve complications (microvascular complications) as well as increased risk of stroke, heart disease, and amputations (macrovascular complications). Although epidemiological studies indicate that reducing blood glucose in patients with T2D reduces their risk of death and morbidity, it has not been possible to unequivocally confirm this finding in large-scale randomised controlled trials (RCT). It is still not clear whether targeting more intensive glycaemic control is better than targeting conventional glycaemic control for reducing mortality or heart disease.
We identified 20 RCTs. A total of 16,106 T2D patients randomised to intensive glycaemic control and 13,880 T2D patients randomised to conventional glycaemic control were included in the analyses. The trials were primarily conducted in Europe and Northern America. The mean duration of the intervention period varied from three days to 12.5 years. The mean age of the participants of the included trials was 62.1 years.
We could not find any significant reduction in either death from any cause or death from heart disease when targeting intensive glycaemic control compared with conventional control. Intensive glycaemic control, however, reduced the risk of amputation of a lower extremity and of microvascular complications while increasing the risk of hypoglycaemia. Targeting intensive glycaemic control did not appear to change the risk of macrovascular complications as a composite outcome (an outcome consisting of several items with importance to macrovascular complications), non-fatal stroke, cardiac revascularization (a procedure to reconstruct damaged heart blood vessels), and peripheral revascularization. In trials exclusively dealing with glycaemic control in the usual care setting, a significant reduction in non-fatal myocardial infarction, in favour of targeting intensive glycaemic control, was shown. However, more trials are needed before firm evidence is established.
We suggest a cautious approach when reducing blood glucose. The balance of benefits and harms when reducing blood glucose should be taken into account. There is a need for more powerful trials to guide the choice of targeting intensive versus conventional glycaemic control in patients with T2D.