Diabetes mellitus and atrial fibrillation-from pathophysiology to treatment

Table 1 Pathophysiologic mechanisms connecting type 2 diabetes mellitus and Atrial Fibrillation

	Involved mechanism	Result
Structural remodelling	Inflammation	Atrial fibrosis and dilatation
	Oxidative stress
	Expression of profibrotic growth factors
	Enhanced collagen synthesis and high fibroblast activity
	Activation of the (RAAS) system
	Obesity and adiposity
Electrical remodelling	Longer activation times	Conduction abnormalities
	Abnormal current densities and refractory periods
	Electromechanical delay
	Affected gap junction function
Autonomic dysfunction	Downsizing of parasympathetic nervous system	Autonomic imbalance
	Upregulation of sympathetic stimuli
Glycemic parameters	Sympathetic activation due to hypoglycaemia	AF susceptibility
	Remodelling due to chronic hyperglycemia
	Oxidative stress and fibrosis due to glycemic fluctuations
	Fibrosis due to adipokines

AF: Atrial fibrillation.

Table 2 The effect of antidiabetic medication in atrial fibrillation

Ref.	Medication	Study design	Effect
Chang et al[51]	Metformin	Non-RCT	Lower risk of new-onset AF (HR: 0.81, 95%CI: 0.76-0.86, P < 0.0001)
Zhang et al[55]	TZD	MA	Approximately 30% lower risk of developing AF compared to controls, only in observational studies
Chang et al[60]	DPP4i	Non-RCT	DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i
Monami et al[66]	GLP1-RA	MA	No effect on AF incidence (OR: 0.87, 95%CI: 0.71-1.05, P = 0.15)
Zelniker et al[71]	SGLT2i	RCT	Reduced AF risk (HR: 0.81, 95%CI: 0.68-0.95, P = 0.009)
Fernandes et al[73]	SGLT2i	MA	Reduced incidence of atrial arrhythmias (OR: 0.81, 95%CI: 0.69-0.95, P = 0.008)
Engström et al[77]	SGLT2i	Non-RCT	SGLT2i modestly reduced AF risk compared to GLP1-RA (adjusted HR: 0.89, 95%CI: 0.81-0.96)
Lee et al[80]	SGLT2i	Non-RCT	Lower risk of incident AF compared to DPP4i (HR: 0.68, 95%CI: 0.56, 0.83, P = 0.0001)

AF: Atrial fibrillation; RCT: Randomized controlled trial; HR: Hazard ratio; CI: Confidence interval; TZD: Thiazolidinedione; MA: Meta-analysis; DPP4i: Dipeptyl peptidase 4 inhibitors; GLP1-RA: Glucagon-like peptide-1 receptor agonist; OR: Odds ratio; SGLT2i: Sodium-glucose cotransporter-2 inhibitors.