People with type 2 diabetes mellitus (T2D) have an increased mortality and morbidity compared to the general population. T2D is characterised by several metabolic defects including 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). Epidemiological studies suggest that reducing blood glucose in people with T2D may reduce the risk of death and morbidity. However, such studies do not represent a reliable methodology to assess the effects of interventions because of the inherent risk of imbalances (which may be hidden and therefore uncorrectable) between groups, other than those resulting from the interventions. It is still not clear whether targeting more intensive glycaemic control is better than conventional glycaemic control in terms of clinical outcomes based on evidence from randomised clinical trials (RCTs).
In this updated Cochrane systematic review, we identified 28 RCTs comparing intensive glycaemic control versus conventional glycaemic control in participants with T2D. A total of 18,717 participants randomised to intensive glycaemic control and 16,195 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. Only two trials were considered to have low risk of bias; we may, therefore, have evaluated RCTs with high risk of overestimating beneficial effects and underestimating harmful effects.
Our analyses did not show any statistically 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 seemed to reduce the risk of non-fatal myocardial infarction, amputation of a lower extremity, and microvascular complications while increasing the risk of severe adverse events and hypoglycaemia. Targeting intensive glycaemic control did not appear to change the risk of non-fatal stroke, cardiac revascularization (a procedure to reconstruct damaged heart blood vessels), and peripheral revascularization. Health-related quality of life did not differ significantly when comparing targeting intensive with conventional glycaemic control.