Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population
Authors' conclusion
Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.
Study context
- Population
- Indian population whole genomes, with PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 non-insulin antidiabetic drugs (NIADs)
- Participants
- 1,029 Indian whole genomes
- Comparison
- PGx allele frequencies in Indians and South Asians vs other global populations
- INDIANSn = 1,029
- Outcome
- PGx variants associated with response to T2D therapy and allele frequency differences across populations
Methodological detailspopulation-specific, in silico network analysis
- Population-specific
- In silico network analysis
Main finding
As reported in the abstract
Common PGx variants associated with response to T2D therapy among Indians
| Group | Known common PGx variants | Predicted deleterious common PGx variants |
|---|---|---|
| INDIANS | 76 | 52 |
INDIANS
Known common PGx variants76
Predicted deleterious common PGx variants52
Further findings
Predicted DDI risk (network analysis of shared PGx genes)
- High DDI risk predicted during coadministration of NIADs with other metabolic disease drugs
Predicted CYP2C19-mediated DDGI risk
- Increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs)
Original publication
Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population. BMJ Open Diabetes Res Care. Published 12 March 2024. doi:10.
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