Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials

The purpose of this study was to explore the relationship between hyperglycaemia in type 2 diabetes and risk of cancer incidence or cancer mortality. We were interested to determine if data from major randomised controlled trials would support a hypothesis that improving glycaemic control may reduce the risk of cancer outcomes. We included major randomised controlled trials conducted with an overall aim of intensified glycaemic control in type 2 diabetes. We abstracted data from published papers and supplemental material and conducted separate meta-analyses of cancer mortality and cancer incidence. Four trials reported cancer mortality for the intensive (222 events in 53,892 person-years) and standard control (155 events in 38,743 person-years) arms (UK Prospective Diabetes Study [UKPDS] 33, UKPDS 34, Action to Control Cardiovascular Risk in Diabetes [ACCORD] and Veterans Affairs Diabetes Trial [VADT]); the summary risk ratio for cancer mortality was 1.00 (95% CI 0.81-1.24; I (2) = 0%). Excluding the UKPDS metformin trial resulted in a pooled risk estimate of 1.03 (95% CI 0.83-1.29; I (2) = 0%). Three trials reported cancer incidence for the study arms (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation [ADVANCE], PROspective pioglitAzone Clinical Trial In macroVascular Events [PROactive], Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes [RECORD]) with 357 events in 47,974 person-years with improved glycaemic control and 380 events in 45,009 person-years in the control arms; the pooled risk ratio for cancer incidence was 0.91 (95% CI 0.79-1.05; I (2) = 0%). Data from large randomised controlled trials of intensified glycaemic control suggest that cancer risk is not reduced by improving glycaemic control in type 2 diabetes. These data therefore do not support the hypothesis that hyperglycaemia is causally linked to increased cancer risk.