Table 3.

Effects of metformin on atrial arrhythmias: reports from clinical trials

Model	Type of study/No. of patients/follow-up	Metformin (dose/duration)	AF incidence	Interpretation		References
Taiwanese DM patients treated with metformin alone vs. other meds (mean age 58 years)	Longitudinal cohort/85,198 metformin users and 560,512 non-users/mean follow-up 5.4 years	Various dose and duration of metformin	- ↓ AF incidence in the first 3 years after diagnosis of DM - HR of 0.81, p < 0.0001	Metformin associated with decreased incidence of AF during the first 3 years after the diagnosis of DM		[44]
Taiwanese DM patients w/ or w/o metformin (mean age 69 years)	Nested case control study/2882 AF and 11,528 controls/mean DM duration 3.9 years	- Various dose - At least 6 months of drug used	- ↓ AF incidence - OR 0.81, 95%CI 0.71–0.95	Metformin associated with decreased new onset AF		[55]
Hospitalized DM patients with AMI w/ or w/o metformin (mean age 56)	Retrospective cohort/40 Metformin alone and 705 others/28-day post AMI	Various dose	- Metformin alone: <-> 28-day AF incidence, OR 1.1 (95%CI 0.3–4.0) - Metformin + other anti-DM drugs: ↓28-day AF incidence, OR 0.2 (95% CI 0.1–0.7)	Metformin in combination with other anti-DM drugs associated with decreased AF incidence 28-day post AMI		[56]
≥ 65 years old Taiwanese DM patients w/ or w/o metformin (mean age 73 years)	Nested case-control/1958 cases and 7832 controls/mean DM duration 8 years	- Various dose - At least 12 months of drug used	- <-> AF incidence - OR 1.01 (0.88–1.15)	Metformin was not associated with decreased AF incidence in elderly DM population		[57]
Patients without DM undergoing cardiac surgery randomized to metformin or placebo (mean age 65 years)	Double-blind, randomized controlled trial/57 to metformin, 57 to placebo/24-h post reperfusion	Metformin 500 mg TID for 3 days before surgery	- <-> 24-h post reperfusion Trop I level and arrhythmia	Short-term metformin pre-surgery did not decrease perioperative myocardial injury or AF in non-DM undergoing cardiac surger		[68]
DM pts undergoing cardiac surgery w/ or w/o metformin (mean age 66 years)	Retrospective matched cohort/metformin 635, non-metformin 648/post-op until hospital discharge	Metformin ≥ 500 mg any time prior to surgery	- <-> post-op AF incidence - post-op AF 26.3% in metformin vs. 30.7% in non-metformin(p = 0.46)	Prior use of metformin in DM patients undergoing cardiac surgery was not associated with decreased post-op AF		[69]

AF atrial fibrillation, AMI acute myocardial infarction, DM diabetes mellitus