Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial

OBJECTIVERandomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality.RESEARCH DESIGN AND METHODSParticipants with type 2 diabetes (n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.1%) were randomly assigned to treatment strategies targeting either A1C 7%.CONCLUSIONSThese analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD