SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study
Authors' conclusion
This study supported the association of SGLT2 inhibition with a reduced risk of AF. The total concentration of lipoprotein particles and particularly the concentration of HDL particles might mediate this association. Further mechanistic and clinical studies research are needed to understand the mediation effects of circulating metabolites especially blood lipids in the association between SGLT2 inhibition and AF.
Study context
- Population
- Genetic instruments for SGLT2 inhibition: variants associated with both SLC5A2 expression and HbA1c
- Comparison
- Genetically predicted SGLT2 inhibition
- Outcome
- AF
Methodological detailstwo-sample, two-step
- Two-sample
- Two-step
Main finding
As reported in the abstract
Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) and atrial fibrillation (AF), OR (95% CI 0.27, 0.97), P = 0.039
0.51
Further findings
T2D (positive control)
- Genetically predicted SGLT2 inhibition and T2D, OR (95% CI 0.45, 0.88), P = 0.006
- 0.63
Mediation by circulating metabolites
- Of 168 circulating metabolites, number associated with both SGLT2 inhibition and AF
- 2
- Effect of SGLT2 inhibition on AF through total concentration of lipoprotein particles ([0.81, 0.96], P = 0.004)
- 0.88
- Mediated proportion via total lipoprotein particles
- 8.03% (95% CI [1.20%, 14.34%], P = 0.010)
- Effect of SGLT2 inhibition on AF through concentration of HDL particles ([0.82, 0.97], P = 0.005)
- 0.89
- Mediated proportion via HDL particles ([1.09%, 13.34%], P = 0.011)
- 7.59%
Original publication
SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study. Cardiovasc Diabetol. Published 17 October 2023. doi:10.
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