Complex interrelationship and therapeutic advances in diabetic patients with atrial fibrillation

Table 1 Effects of different antidiabetic treatments on atrial fibrillation

Drug class	Effect on AF	Pathogenetic mechanisms	Type of study	Ref.
Metformin	Mostly positive	Anti-inflammatory (activation of AMPK), anti-oxidant, inhibition of RAGE, improved mitochondrial function and calcium homeostasis	Non-RCTs, animal studies	[102,104-108]
Thiazolidinediones	Mostly positive	Anti-inflammatory (PPAR-γ and angiotensin II), anti-fibrotic	Non-RCTs, meta-analysis, RCT	[109,112,113]
DPP-4 inhibitors	Mostly neutral	Anti-inflammatory, anti-oxidant, improved calcium regulation	RCTs, non-RCTs, meta-analysis	[114,116-119]
GLP-1 receptor agonists	Positive	Weight loss, anti-inflammatory, reduced epicardial adiposity	RCTs, non-RCTs, meta-analyses	[122-127]
SGLT2 inhibitors	Positive	Anti-inflammatory (AMPK phosphorylation), improved mitochondrial function, anti-oxidant, reduced EAT volume and thickness	RCTs, non-RCTs, meta-analyses, animal studies	[128-138]
Insulin	Negative	Vascular inflammation, smooth muscle proliferation, endothelial dysfunction, hypoglycemia induced-autonomic nervous system activation	Non-RCT, meta-analysis	[114,139]

AF: Atrial fibrillation; DPP-4: Dipeptidyl peptidase-4; GLP-1: Glucagon-like peptide-1; SGLT2: Sodium-glucose cotransporter 2; AMPK: AMP-activated protein kinase; RAGE: Receptor of advanced glycation end products; PPAR-γ: Peroxisome proliferator-activated receptor-γ; EAT: Epicardial adipose tissue; RCT: Randomized controlled trial.