Poor glycaemic control in type 2 diabetes: a conspiracy of disease, suboptimal therapy and attitude

Glycaemia in type 2 diabetes is difficult to manage long‐term, and despite a wealth of epidemiological evidence, there continued to be doubts, until recently, as to whether intensive glucose control was beneficial. The publication of robust prospective evidence from the United Kingdom Prospective Diabetes Study1 in September 1998 marked a seminal change. In type 2 diabetes, there was extensive epidemiological data suggesting that complications were linked to glycaemic exposure,2 but the UGDP (University Group Diabetes Program)3 trial had raised doubts about the safety of sulphonylureas in reducing plasma glucose. The DCCT4 showed in 1993 that tight glycaemic control reduced microvascular complications in type 1 diabetes. The UKPDS provided evidence that tight control was beneficial in type 2 diabetes: patients in an intensively treated group achieved a median HbA1c of 7.0% at 10 years compared to 7.9% in those in a conventionally treated group. This improvement in glycaemic control was associated with a 12% reduction in any diabetes end‐points ( p =0.029) and a 25% reduction in microvascular end‐points ( p =0.0099).1 However the achieved HbA1c values of the trial were neither the aim of the trial, nor the best glycaemic control that could be achieved, because one of the aims was to address the question of the efficacy and safety of monotherapies. Thus the protocol required, in those randomized to sulphonylurea therapy, that, once the maximum dose was reached, the fasting plasma glucose could rise to 15 mmol/l or to the advent of symptoms before additional pharmacological agents were introduced. The epidemiology analysis of the UKPDS suggested that there was no discernible threshold for the improved outcome with lower glycaemia. However, in clinical practice optimal glycaemic control is difficult to obtain. Prospective randomized studies have achieved median HbA1c levels of 7.1%5 and 7.0% in intensively treated patients, …