Evidence mapPaperPMID 38471670Full record

ArticleBMJ open diabetes research & care2024

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.

Ambily Sivadas, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra and 6 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Molecular subtypes and survival patterns of endometrial cancer in a South Indian cohort.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
    Article
  2. Metformin Alone and in Combinations Alter the Methylation Patterns ofEndocrine, metabolic & immune disorders drug targets · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Ambily SivadasSt John's Research Institute, Bangalore, Karnataka, India a.kurpad@sjri.res.in ambily.s@sjri.res.in.ORCID 0000-0001-5694-3866
S SahanaCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Bani JollyCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Rahul C BhoyarCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Abhinav JainCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Disha SharmaCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Mohamed ImranCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Vigneshwar SenthivelCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Mohit Kumar DivakarCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Anushree MishraCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Arpita MukhopadhyaySt John's Research Institute, Bangalore, Karnataka, India.
Greg GibsonGeorgia Institute of Technology, Atlanta, Georgia, USA.
Km Venkat NarayanRollins School of Public Health, Atlanta, Georgia, USA.ORCID 0000-0001-8621-5405
Sridhar SivasubbuCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Vinod ScariaCSIR Institute of Genomics and Integrative Biology, New Delhi, India.
Anura V KurpadSt John's Medical College, Bangalore, Karnataka, India a.kurpad@sjri.res.in ambily.s@sjri.res.in.
Institute of Genomics and Integrative Biology · INSt.John's Medical College Hospital · INGeorgia Department of Public Health · USGeorgia Institute of Technology · US

Funding

DBT-Wellcome Trust India Alliance IA/E/19/1/504945Wellcome Trust
6 · The paper itself

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.

Indexed as

Diabetes Mellitus, Type 2Hypoglycemic AgentsGene FrequencyHumansInsulinInsulin, Regular, HumanPharmacogenomic VariantsHypoglycemic AgentsInsulinInsulin, Regular, HumanDiabetes Mellitus, Type 2GenomicsIndians

Identifiers

PMID38471670
PMCPMC10936492
OpenAlexW4392696386

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.