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

Abstract

AimsTo 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.MethodsData 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.ResultsA 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.ConclusionsOngoing poorer glucose control was associated with CV events; hypoglycaemia was not associated with CV‐specific/all‐cause death.

Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD) therapy by initiating insulin versus enhancing OAD therapy in patients with type 2 diabetes: A nationwide population‐based, propensity‐score‐matched cohort study

“…Hypoglycaemia is a major undesired effect of insulin therapy, and may play a role in a causal pathway between insulin therapy and risks of CVD and mortality. There is supporting evidence linking hypoglycaemia with increased risks of CVD and mortality in patients with T2DM or prediabetes, but one study reported no significant relationship between severe/symptomatic hypoglycaemic events and CVD‐specific/all‐cause mortality in patients with T2DM starting insulin therapy . In the present study we found that the increased risks of clinical outcomes associated with insulin therapy became lower or even vanished after hypoglycaemia was adjusted for in the analyses, which provides the supporting evidence for the potential effect of hypoglycaemia on risks of CVD and mortality, and indicates the use of insulin per se may not be associated with increased risks of CVD and mortality (Table , Table S7).…”

Clinical correlates of hypoglycaemia over 4 years in people with type 2 diabetes starting insulin: An analysis from the CREDIT study

“…We describe the incidence of hypoglycaemia, predictors and in‐study explanatory factors for such events, their relationship to the trajectory of HbA1c and relationship with insulin regimen. We have previously described the evolution of individually chosen insulin regimens and their relation to glucose control, together with analyses of predictors of weight change, glucose control and a description of the relationship of the latter to cardiovascular events …”

“…The CREDIT core study was funded by Sanofi. The core team, investigators and participants are acknowledged elsewhere and are again thanked. The authors also thank Tom Claus of PAREXEL for writing assistance funded by a grant from Sanofi (Paris).…”

“…In the present study, we aimed to: (1) evaluate the characteristics, both at 1 year and 4 years, that were associated with documented symptomatic hypoglycaemia; (2) understand the nature of those relationships in routine care, particularly for glucose control; (3) discover if those characteristics would apply to severe hypoglycaemia; and (4) understand how the evolution of insulin regimen (and oral agents) and insulin dose affected hypoglycaemia rates. Previously, we have reported the characteristics of people in the CREDIT study that are associated with weight gain, and those associated with good glycaemic control, and described the relationship between blood glucose control and cardiovascular events …”

Basal insulin therapy: Unmet medical needs in Asia and the new insulin glargine in diabetes treatment

“…According to the Action to Control Cardiovascular Risk in Type 2 Diabetes study, intensive glycemia control increased the occurrence of severe hypoglycemia in type 2 diabetes patients at high risk of cardiovascular events, but might not directly account for the increased death. However, improved glycemic control for the long term, which was investigated in the Cardiovascular Risk Evaluation in People with Type 2 Diabetes on Insulin Therapy study over 4 years, facilitated the reduction of cardiovascular events.…”