Table 2 Effects of metformin on atrial arrhythmias: reports from in vivo studies

Non-DM dogs with atrial rapid pacing (1200 bpm for 6 h)

100 mg/kg/days for 2 weeks

↑↑AMPK

-↑PPARα, PGC-1α, VLCAD, CPT-1

–

–

–

–

↑AERP ↓AERPd

↓FFA/TG /lipid deposition in LAA

–

Metformin improved EP disorders caused by atrial rapid pacing via ↓lipid accumulation and promoted FAO in AF models through AMPK/PPAR-α/VLCAD pathway

[41]

Non-DM dogs with rapid atrial pacing (400 bpm for 6 weeks)

100 mg/kg/days for 1 week prior then 6 weeks

–

↓ in LA/EAT

–

– ↑APN, adipoR1 – ↓ IL-6, NF-kB, TNFα, TGFβ1

–

↑AERP ↓AERPd

↓LA fibrosis and EAT

↓

Metformin reduced AF and atrial fibrosis by inhibited ROS/NF-kB, reduced epicardial fat, pro-inflammatory adipokines, and upregulated adiponectin in LA/EAT

[45]

Non-DM dogs with rapid atrial pacing 400 bpm

100 mg/kg/days for 1 week then pace for 180/ 360 min (acute)

–

–

–

–

↑

↔

AERPd

–

–

Metformin reduced AF by preventing adverse electrical remodeling via increase AMPK and Cx43 expression in chronic AF model. Metformin mildly increased Cx43 in acute pacing and could not attenuate AERPd

[42]

100 mg/kg/days with pace for 6 weeks (chronic)

↑AMPK

↔ mito-chondrial morphology

–

–

–

↑↑

↑AERP ↓AERPd

↔Irregular myocardial fibers

↓

GK T2DM rats

300 mg/kg/days for 3 months

- ↔ SK1, ↑SK2,↓SK3

-↑SK current

-↓distorted current-voltage relationship

↓ APD

↓ Atrial myofilament irregularity and fibrosis

↓

Metformin reduced atrial arrhythmia in DM GK rats via decreased atrial remodeling and normalized APD via restoring SK current

[53]