The Effect of SGLT2 Inhibition on Brain-related Phenotypes and Aging: A Drug Target Mendelian Randomization Study
Authors' conclusion
Our study supported that SGLT2 inhibition increases father's attained age, cognitive function, and intelligence, which was mediated through brain images of different brain regions. Future studies are needed to investigate whether a similar effect could be observed for users of SGLT2 inhibitors.
Study context
- Population
- Genetic variants associated with SLC5A2 expression (GTEx, eQTLGen) and hemoglobin A1c (HbA1c) (UK Biobank); outcomes from GWAS of parental longevity, epigenetic clocks, cognitive function and intelligenceGWAS summary data
- Comparison
- Genetically proxied SGLT2 inhibition
- Outcome
- Chronological age, biological age and cognition, and mediation by brain imaging-derived phenotypes (IDPs)
Methodological detailstwo-step Mendelian randomization (MR), genetic proxies of SGLT2 inhibition (SLC5A2 expression and HbA1c)
- Two-step MR
- Genetic proxies of SGLT2 inhibition (SLC5A2 expression and HbA1c)
Main finding
As reported in the abstract
Effects of SGLT2 inhibition
Father's attained age, years of life increase per SD (6.75 mmol/mol) reduction in HbA1c
6.21
95% CI 1.27–11.15
Cognitive function, beta (95% CI 0.03-0.31)
.17
Intelligence, beta (95% CI 0.19-0.75)
.47
Further findings
Mediation by brain imaging-derived phenotypes (IDPs) (two-step MR)
- Chronological age: 2 IDPs mediators, total proportion of mediation
- 22.6%
- Cognitive function: 4 IDPs mediators, total proportion of mediation
- 61.6%
- Intelligence: 5 IDPs mediators, total proportion of mediation
- 68.6%
Original publication
The Effect of SGLT2 Inhibition on Brain-related Phenotypes and Aging: A Drug Target Mendelian Randomization Study. J Clin Endocrinol Metab. Published 13 September 2024. doi:10.
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