Genetic and clinical factors associated with metformin plasma concentrations following an acute metformin challenge
Authors' conclusion
These findings represent the first GWAS of metformin plasma concentrations and provide a novel resource for future studies of metformin pharmacogenetics.
Study context
- Population
- Participants of SUGAR-MGH, an ancestrally diverse cohort, who completed a standardized acute metformin challengecompleted metformin challenge
- Participants
- 745 participants
- Outcome
- Plasma metformin concentrations and associated clinical and genetic factors
Methodological detailscohort with genome-wide association study (GWAS), ancestrally diverse cohort, standardized acute metformin challenge, genome-wide association study
- Cohort with GWAS
- Ancestrally diverse cohort
- Standardized acute metformin challenge
- Genome-wide association study
Main finding
As reported in the abstract
Plasma metformin concentration
- Older age associated with higher metformin concentration (β per year; p = 0.02)
- β=2.5 ng/mL per year
- Lower eGFR associated with higher metformin concentration (p = 4.5 × 10-4)
- β=−3.5 ng/mL per ml/min/1.73m2
- Lower BMI associated with higher metformin concentration (p = 1.3 × 10-4)
- β=−7.3 ng/mL per kg/m²
- African vs European ancestry: lower metformin concentration (p = 0.036)
- β=−72.6 ng/mL
- GWAS: African ancestry-specific variants significantly associated with higher metformin concentration (p < 5 × 10-8)
- 4
Observational data: associations, not effects.
Further findings
Glycemic response endpoints after metformin challenge (fasting glucose at Visit 2, change in HOMA-IR, change in fasting insulin)
- Top metformin-concentration variants not associated with glycemic response endpoints
Original publication
Genetic and clinical factors associated with metformin plasma concentrations following an acute metformin challenge. J Clin Endocrinol Metab. Published 3 July 2026. doi:10.
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