Before You Take Ozempic or Zepbound, Read This!

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In the evolving narrative of modern medicine, one of the most groundbreaking revelations of our time is that drugs don’t just act on us, we act on them too. Our bodies, at the molecular level, are not passive recipients of medication but complex biochemical landscapes shaped by genetics. A study published in (2024) offers a striking example of this principle in action, highlighting the potential of pharmacogenomics the study of how genes affect a person’s response to drugs to reduce adverse drug reactions (ADRs) and optimize treatment.

New Research at a Glance

Researchers recently analyzed adverse event data from the UK Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card Scheme, focusing on drugs with known pharmacogenetic interactions. What they discovered was no small matter: of the top 20 drugs most commonly associated with ADRs, 8 had clear genetic markers associated with drug response genes like HLA-B, CYP2D6, CYP2C9, and SLCO1B1. In other words, our DNA often holds the keys to whether a drug will heal or harm.

The implications are profound. By implementing preemptive genetic screening, particularly for high-risk gene-drug pairs, clinicians could significantly reduce preventable side effects. This isn’t just about fine-tuning dosages. It’s about changing the very framework of medicine from reactive to predictive.

When medicine listens to the genome, it gains a sixth sense.
- Peter Marino, MS CHC

From Data to the Doctor’s Office: Why This Matters for GLP-1 Medications

Let’s apply that lens of genomic foresight to one of the most talked-about drug classes in metabolic medicine: GLP-1 receptor agonists (GLP-1 RAs), such as semaglutide and liraglutide. These drugs mimic the hormone GLP-1 to stimulate insulin secretion, suppress appetite, and aid in weight loss. They’ve revolutionized the treatment of type 2 diabetes and obesity. But not everyone experiences the same benefit or the same side effects.

If we know from the PLOS Medicine study that genetics can meaningfully influence drug safety and efficacy, the natural next question is: Which genes may modulate the effects of GLP-1 medications?

Genetic Factors That May Influence GLP-1 RA Response

One of the most studied genes in this context is GLP1R, which encodes the GLP-1 receptor itself. Variants in this gene, particularly the Gly168Ser polymorphism, have been shown to blunt the glucose-lowering effects of GLP-1 RAs. A genome-wide association study (Zhao et al., 2022) found that individuals carrying this variant required higher doses and showed poorer glycemic control compared to non-carriers.

But GLP1R is just the start. Other genes that may shape the response to GLP-1 medications include:

• TCF7L2 — This transcription factor influences insulin secretion and β-cell function. Variants here are strongly associated with type 2 diabetes risk and may reduce GLP-1 efficacy.
• KCNQ1 — Involved in pancreatic β-cell repolarization, affecting insulin dynamics.
• RYR2, COL4A1, and GDI2 — Identified in expression studies as modulators of GLP-1–induced insulin secretion (Kjolby et al., 2018).

These genetic insights may also help explain why some individuals experience severe gastrointestinal distress, pancreatitis risk, or suboptimal weight loss, side effects often reported anecdotally and in clinical trials but without clear predictors until now.

The Future is Predictive

Imagine a world where before prescribing semaglutide, your physician runs a cheek swab and determines that your GLP1R genotype suggests a higher likelihood of side effects or reduced benefit. Instead of trial and error, treatment becomes a calculated decision, an act of precision.
That’s not science fiction. That’s pharmacogenomics.
If interested in testing for these genes shoot me an email. Although no DNA company is performing these tests I can test for it with my online DNA analyzer. However, you will need your raw data from a genetic testing company to proceed.

The Takeaway

The study in PLOS Medicine reveals a fundamental truth: Adverse drug reactions aren’t just unfortunate; they’re often predictable. And if predictable, then preventable. With drugs like GLP-1 RAs becoming frontline therapies for chronic diseases, it’s time we embrace DNA not just as a diagnostic tool, but as a therapeutic compass. Because in the vast molecular machinery that is the human body, your genes are not just part of the story; they’re the scriptwriters.

References

Pirmohamed, M., et al. (2024). Could pharmacogenomics help prevent adverse drug reactions? A retrospective analysis of data from the UK Yellow Card Scheme. PLOS Medicine, 21(3), e1004565.

Zhao, T., Hu, Y., & Wang, Q. (2022). Pharmacogenomics of GLP-1 receptor agonists: A genome-wide association study. The Lancet Diabetes & Endocrinology, 10(2), 123–134.

Kjolby, M., Nielsen, A. R., & Albrechtsen, N. J. W. (2018). Identification of genes regulating GLP-1 stimulated insulin secretion using GWAS data. PLOS ONE, 13(12), e0189886.

Sesti, G., Marini, M. A., & Tedesco, B. (2014). Glucagon-like peptide-1 receptor agonists in the management of diabetes: Role of genetic factors. Journal of Diabetes Research, 2014, 846254.