Controversy has emerged concerning the risks associated with
glitazone therapy in type 2 diabetes, specifically bone fracture
and myocardial infarction. Results from the Action to Control
Cardiovascular Risk in Diabetes (ACCORD) study have stimulated
debate about appropriate glycated haemoglobin (HbA1c) targets.
This article examines the context for glitazone therapy in
patients with type 2 diabetes, the risks associated with
pioglitazone and rosiglitazone, and arguments for targeting
HbA1c at the threshold of 7%.
Pioglitazone and rosiglitazone can be employed as oral therapy
in patients with type 2 diabetes and preserved endogenous
insulin secretion. Potential benefits and risks of each agent
should be considered. An acceptable initial target for HbA1c
is 7%. Lowering HbA1c to 6.5% did not reduce macrovascular
complications in patients with type 2 diabetes, but did reduce
new or worsening nephropathy. Aggressive therapy aiming
to lower HbA1c to <6% in patients with type 2 diabetes at
especially high risk of cardiovascular disease may lead to a
higher risk of mortality.
Patients with type 2 diabetes undergo a transition over time from an initial state of predominant insulin resistance to progressive impairment of beta cell function. While beta cell secretion of insulin is preserved, lifestyle measures to reduce insulin resistance are indicated, and additional drug therapy is often necessary. Metformin and sulphonylureas are common first and second line therapies. Options to intensify therapy include the use of a glitazone or an alternative agent such as exenatide, or to commence insulin.
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