ArticleBMJ open diabetes research & care2024
Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.
Article in BMJ open diabetes research & care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
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- Article
- Dietary Modulation of CYP3A4 and Its Impact on Statins and Antidiabetic Drugs: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- From Control to Cure: Insights into the Synergy of Glycemic and Antibiotic Management in Modulating the Severity and Outcomes of Diabetic Foot Ulcers.International journal of molecular sciences · 2025Review
- Cataloging Actionable Pharmacogenomic Variants for Indian Clinical Practice: A Scoping Review.Journal of xenobiotics · 2025Review
- Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities.Diabetologia · 2025Review
- Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.Biomolecules · 2025Review
- Lessons Learned From Epidemiology of Type 2 Diabetes in South Asians: Kelly West Award Lecture 2024.Diabetes care · 2025Article
- Implementing pharmacogenetic testing to optimize proton-pump inhibitors use among Indian population based on CPIC-CYP2C19-PPI dosing guidelines: The need of the hour.Indian journal of pharmacology · 2024Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionGenetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. RESEARCH DESIGN AND
methodsWe mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test.
resultsOverall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs).
conclusionsIndians 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.
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