Update on evidence-based clinical application of sodium-glucose cotransporter inhibitors: Insight to uncommon cardiovascular disease scenarios in diabetes

Table 3 Summary of clinical studies on sodium-glucose co-transporter inhibitors in atrial fibrillation/atrial flutter and other arrhythmias patients

Ref.	Type of article	Journal and published time	Drugs	Aim of study	Inclusive population	Intervention cycle	Number of cases	Main conclusion
Li et al[33]	Meta- Analysis	Front Endocrinol (Lausanne), 2021	Dapagliflozin (10 mg/d), canagliflozin (100/300 mg/d), empagliflozin (10/25 mg/d), ertugliflozin (5/15 mg/d), sotagliflozin (200/400 mg/d), or placebo	To investigate whether SGLT2i use is associated with lower risks of AF/AFL	Patients with randomized placebo-controlled trials registered in comparing SGLT2is with matching placebo including recorded AF/AFL outcomes	60 d to 5.2 years	66685	SGLT2i use is associated with a 19.33% lower rate of SAEs of AF/AFL compared with the placebo
Hsiao et al[34]	Multicenter Study	J Clin Endocrinol Metab, 2022	Dapagliflozin (10 mg/d), empagliflozin (10 mg/d), canagliflozin (100 mg/d), or liraglutide or dulaglutide	To determine the comparative risk of new-onset AF with SGLT2is vs GLP-1RAs in Asian patients with T2D in a real-world setting	New-onset AF in patients with T2D	3.0 years	16566	SGLT2is were associated with lower risk of new-onset AF compared with GLP-1RAs among patients with T2D in a real-world practice
Zhuo et al[35]	Cohort study	JAMA Netw Open, 2022	Dapagliflozin (10 mg/d), empagliflozin (10 mg/d), canagliflozin (100 mg/d), or DPP-4i/GLP-1RA	To examine incident AF with initiation of an SGLT2i compared with initiation of a DPP-4i or a GLP-1RA among older adults (age ≥ 66 years) with T2D in routine clinical practice	Older adults with T2D who had no history of AF	April 1, 2013 to December 31, 2018	165984	SGLT2is reduced risk of incident AF compared with a DPP-4i or GLP-1RA
Pandey et al[36]	Meta-analysis	J Am Heart Assoc, 2021	Empagliflozin (10/20 mg/d), dapagliflozin (2.5/5/10 mg/d), canagliflozin (100/300 mg/d), ertugliflozin (5/15 mg/d), sotagliflozin (200/400 mg/d), or placebo	To determine whether SGLTis reduce AF and whether a history of AF modifies the effect of SGLTis on the composite of HF hospitalization or cardiovascular death	Patients regardless of prior AF history or other comorbidities	24-304 wk	75279	SGLTis may reduce AF events and likely reduce HF hospitalization/cardiovascular death to a similar extent in patients with and without AF
Zheng et al[37]	Meta- analysis	Pacing Clin Electrophysiol, 2024	Canagliflozin (100/300 mg/d), dapagliflozin (10 mg/d), empagliflozin (10/25 mg/d), or placebo	To investigate the effect of SGLT2is on the incidence of cardiovascular disease events in patients with AF	Patients with AF	2.3 to 3.3 years	38529	SGLT2is were associated with a lower incidence of cardiovascular disease events, especially HF hospitalization, in patients with AF
Fernandes et al[38]	Meta-analysis	Heart Rhythm, 2021	Dapagliflozin (2.5/5/10 mg/d), canagliflozin (100/300 mg/d), empagliflozin (10/25 mg/d), ertugliflozin (5/15 mg/d), or placebo	To evaluate the association of SGLT2is with arrhythmias in patients with T2D or HF	Patients with T2D or HF	24 wk to 5.7 years	63166	SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and sudden cardiac death in patients with T2D

AF: Atrial fibrillation; AFL: Atrial flutter; CREDENCE: Canagliflozin and renal events in diabetes with established nephropathy clinical evaluation; DELIVER: Dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure; DPP-4i: Dipeptidyl peptidase-4 inhibitor; GLP-1RA: Glucagonlike peptide-1 receptor agonist; HF: Heart failure; SAEs: Serious adverse events; SGLT1/2i: Sodium-glucose co-transporter-1/2 inhibitors; SGLT2i: Sodium-glucose co-transporter-2 inhibitors.