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


METHODS
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.


RESULTS
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; I² = 0%). Excluding the UKPDS metformin trial resulted in a pooled risk estimate of 1.03 (95% CI 0.83-1.29; I² = 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; I² = 0%).


CONCLUSIONS
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.
Johnson
J A
JA
Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada. jeff.johnson@ualberta.ca
Bowker
S L
SL
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D009369:Neoplasms / Q000097:blood / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone