Diabet. Med. 27, 309–317 (2010)

Aims  Baseline glycated haemoglobin (HbA_1c) concentrations vary between clinical trials of glucose‐lowering agents and this may affect interpretation of clinical efficacy. The objective of this study is to quantify the relationship between baseline HbA_1c and reduction of HbA_1c in clinical trials.

Methods  PubMed literature searches from 1991 to 2007. Randomized controlled studies with placebo‐controlled or comparator arms [≥ 9 patients in the intent‐to‐treat (ITT) population] ranging in duration from 23 to 52 weeks, in which baseline and change in glycated haemoglobin (HbA_1c) were reported. The relationship between baseline HbA_1c and change in HbA_1c was analysed by a weighted least‐squared regression model accounting for ITT population and variance of HbA_1c change. Fourteen per cent of independently abstracted studies met the selection criteria.

Results  Meta‐analysis from 59 clinical trials (8479 patients) produced weighted R² of 0.35 (P < 0.0001) for the association of baseline HbA_1c and absolute change in HbA_1c. Subanalysis of eight metformin clinical trials demonstrated a stronger association [weighted R² of 0.67 (P = 0.0130)]. Exclusion of metformin clinical trials from the overall meta‐analysis (n = 51) yielded a weighted R² of 0.31 (P < 0.0001). Subanalyses of clinical trials of glucose‐lowering therapies predominantly targeting fasting (n = 37) or postprandial (n = 22) blood glucose produced weighted R² values of 0.27 (P < 0.001) and 0.42 (P < 0.005), respectively.

Conclusions  These data demonstrate a positive relationship between baseline HbA_1c and the magnitude of HbA_1c change across 10 categories of glucose‐lowering therapies, irrespective of class or mode of action. These observations should be considered when assessing clinical efficacy of diabetes therapies derived from clinical trials.