Pharmacogenomics could personalize tirzepatide therapy for diabetes and atherosclerosis | Research

The takeaway

Genetic variants influencing GIP and GLP-1 receptor pathways, T2DM susceptibility, and atherosclerosis risk may explain interindividual variability in tirzepatide response, supporting precision medicine approaches.

Genetics explain variable response
Pharmacogenomic variants in GIP/GLP-1 pathways may determine why some patients respond dramatically to tirzepatide while others see minimal benefit

What the researchers found

Pharmacogenomic variants in GIP/GLP-1 receptor pathways influence tirzepatide response. Genetic susceptibility genes for T2DM and AS overlap with drug response pathways. Precision subtyping potential for individualized therapy.

Why it matters

Not everyone responds equally to tirzepatide. Understanding the genetic basis of response variability could enable prescribers to identify the right patients for the right drug at the right dose—the goal of precision medicine.

How the study worked

Systematic narrative review of pharmacogenomic variants, drug response genes, and genetic susceptibility data for tirzepatide, T2DM, and atherosclerosis.

What this study cannot tell us

Review without primary data. Many proposed pharmacogenomic associations are theoretical. Clinical validation of genetic predictors is lacking.

How to read the evidence

Narrative review proposing pharmacogenomic framework. Theoretical basis strong but clinical validation needed.

When this study was published

Published in 2025.

The bigger picture

As GLP-1/GIP drugs become first-line treatments, pharmacogenomic-guided prescribing could optimize outcomes while avoiding ineffective treatment in genetic non-responders.

Questions still open

Which genetic variants most strongly predict tirzepatide response?
Should genetic testing precede tirzepatide prescribing?
Could pharmacogenomics explain differential weight loss outcomes?

Common questions

Why do some people respond better to tirzepatide than others?

Genetic differences in the receptors tirzepatide targets (GIP and GLP-1) and in the enzymes that process the drug may explain why response varies between individuals. This review maps these genetic factors to support future personalized prescribing.

Could a genetic test predict my response to tirzepatide?

Not yet, but this is the goal of pharmacogenomic research. In the future, a genetic test might identify which patients will benefit most from tirzepatide versus semaglutide or other options, enabling truly personalized obesity and diabetes treatment.

Read the original research

Pharmacogenomics of Tirzepatide: Genomic Insights into Dual GIP/GLP-1 Agonist Response in Type 2 Diabetes and Atherosclerosis.

Pharmaceuticals (Basel, Switzerland), 18(9)

View on PubMed ↗Publisher’s paper ↗

Citation

Song, Zihang; Tang, Yifan; Peng, Mao; Han, Ruoyu; He, Pingping. (2025). Pharmacogenomics of Tirzepatide: Genomic Insights into Dual GIP/GLP-1 Agonist Response in Type 2 Diabetes and Atherosclerosis.. Pharmaceuticals (Basel, Switzerland), 18(9). https://doi.org/10.3390/ph18091261