Relationship of glycaemic control and hypoglycaemic episodes to 4‐year cardiovascular outcomes in people with type 2 diabetes starting insulin

AIMS: To examine the relationships between glycated haemoglobin (HbA1c) and cardiovascular (CV) events in people beginning insulin in routine clinical practice in Europe, North America and Asia in a non‐interventional study, the Cardiovascular Risk Evaluation in people with Type 2 Diabetes on Insulin Therapy (CREDIT) study. METHODS: Data on 2999 people were collected prospectively over 4 years from physician reports. The primary outcome was the composite of stroke or myocardial infarction (MI) or CV‐specific death. Events were blindly adjudicated. The relative hazards of CV events were described from Cox proportional hazards models incorporating patient risk factors, with updated average HbA1c as a time‐dependent covariate. The relationship of severe and symptomatic hypoglycaemia (collected during the 6 months before yearly ascertainment) with CV and all‐cause mortality was examined. RESULTS: A total of 147 primary events were accrued during up to 54 months of follow‐up. In all, 60 CV‐specific deaths, 44 non‐fatal MIs and 57 non‐fatal strokes occurred, totalling 161 events. There was a significant positive relationship between updated mean HbA1c and primary outcome: hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.12–1.40; p < 0.0001]. CV death [HR 1.31 (95% CI 1.10–1.57); p = 0.0027] and stroke [HR 1.36 (95% CI 1.17–1.59); p < 0.0001] were both strongly associated with HbA1c, while MI was not [HR 1.05 (95% CI 0.83–1.32)]. One or more severe hypoglycaemic episodes affected 175 participants, while 1508 participants experienced one or more symptomatic hypoglycaemic events. We found no relationship between severe/symptomatic hypoglycaemic events and CV‐specific/all‐cause death. CONCLUSIONS: Ongoing poorer glucose control was associated with CV events; hypoglycaemia was not associated with CV‐specific/all‐cause death.