Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and...

Area of Science:

• Cardiology
• Endocrinology
• Pharmacology

Background:

• Type 2 diabetes mellitus (T2DM) management aims to reduce major adverse cardiovascular events (MACE).
• The impact of achieved glycemic control (HbA1c levels) on MACE risk across various antidiabetic therapies (ADTs) requires comprehensive assessment.

Approach:

• A systematic review and network meta-analysis of randomized controlled trials (RCTs) were conducted.
• Data from 126 RCTs involving 270,874 participants were analyzed using random-effects models and meta-regression.
• The study assessed MACE and all-cause mortality in T2DM patients treated with marketed ADTs.

Key Points:

• Sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and pioglitazone demonstrated significant MACE risk reduction compared to placebo.
• Achieving HbA1c ≤ 7.0% with these specific drug classes was associated with a 9% reduction in MACE risk (adjusted HR 0.91).
• This glycemic control benefit did not extend to all ADTs and did not impact all-cause mortality.

Conclusions:

• Lowering glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with reduced MACE risk in T2DM.
• These specific therapies offer cardiovascular benefits independent of their effect on all-cause mortality.