[Glycemic control and cardiovascular benefit: What do we know today?]

Area of Science:

• Endocrinology
• Cardiology
• Pharmacology

Background:

• Debate continues on whether targeting normal glycated hemoglobin levels reduces cardiovascular events in advanced type 2 diabetes.
• Major trials like ACCORD, ADVANCE, and VADT offer new insights into glucose-lowering therapy effects.

Purpose of the Study:

• To analyze the distinct microvascular and macrovascular effects of intensive glucose-lowering therapies.
• To evaluate the cardiovascular benefits of specific antidiabetic drugs, like pioglitazone, in patients with advanced type 2 diabetes and macroangiopathy.

Main Methods:

• Review of findings from large-scale trials including ACCORD, ADVANCE, VADT, DIS, UKPDS, and PROactive.
• Analysis of the impact of intensive glycemic control versus drug-specific pleiotropic effects on cardiovascular outcomes.

Main Results:

• Intensive glycemic control effectively reduces microvascular complications (e.g., nephropathy) but shows doubtful macrovascular benefits.
• Early intensive glucose-lowering therapy may yield long-term cardiovascular benefits (1-2 decades), as suggested by DIS and UKPDS.
• The PROactive trial demonstrated cardiovascular benefits of pioglitazone in advanced diabetes, attributed to its pleiotropic effects rather than glycemic control.

Conclusions:

• Microvascular and macrovascular complications require separate consideration in diabetes management.
• Pleiotropic effects of drugs like pioglitazone on insulin resistance, lipids, blood pressure, and inflammation are crucial for cardiovascular risk reduction.
• Future drug therapy decisions necessitate integrating these pleiotropic effects, supported by extensive outcome trial data, which is currently lacking for most antidiabetic drugs.