Diabetes

Sulfonylureas

Among the oldest diabetes drugs still in wide use, and a clean example of a real pharmacogenomic effect that guidelines deliberately decline to act on — which is more useful to know than one they do act on.

What this drug connects to

The genes involved

CYP2C9

Type 2 Diabetes →

A real metabolic effect that guidelines still say not to act on. The reduced-function CYP2C9 alleles slow the clearance of gliclazide, glimepiride and other sulfonylureas, so blood levels run higher. The Dutch Pharmacogenetics Working Group reviewed this and recommends no dose adjustment: a meta-analysis of 2,769 patients found no significant increase in sulfonylurea-induced hypoglycaemia for CYP2C9*3, and where levels do run higher the added effectiveness offsets the risk. Worth knowing precisely because the gap between "measurable in the blood" and "change what you prescribe" is where most pharmacogenomic overclaiming happens.

Dutch Pharmacogenetics Working Group (DPWG) guidance on CYP2C9 and sulfonylureas; meta-analysis of CYP2C9*3 and sulfonylurea-induced hypoglycaemia, 2,769 patients

In the news

2026-07-27 · Disentangling Sex Differences in Sulfonylurea Drug Response With Genome-Wide Association Studies in Individuals With Type 2 Diabetes. Clinical Pharmacology and Therapeutics. 2026. DOI:10.1002/cpt.70381

First sex-stratified sulfonylurea GWAS finds men and women respond through different genes entirely

The first sex-stratified GWAS of HbA1c response to sulfonylureas (871 ACCORD trial participants) found different genome-wide significant loci depending on whether sex was combined or split: KAZN, KIF2B, SLC39A10 and SPINK5 combined-sex; CRACR2A, KCNK2 and TENM2 male-only; NACPH2 female-only -- a pooled-sex study would have missed the sex-specific signals entirely. One replicated variant, rs6471250-C, was significantly associated with reduced peak insulin response to a single glipizide dose in males (p=0.035) but not females (p=0.40) in a functional follow-up cohort -- a genetic effect that is sex-specific not just statistically but functionally.

Variants MyGeneLog™ reports for these genes

These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.

Omega-3 fatty acid levels

CYP2C9 · rs55891451

X-11787 levels

CYP2C9 · rs9332172

Warfarin maintenance dose

CYP2C9 · rs4918798

X-11787 levels

CYP2C9 · rs1934963

X-21849 levels

CYP2C9 · rs9332217

X-17654 levels

CYP2C9 · rs1934969

Appendicular lean mass

CYP2C9 · rs28371678

Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial protein levels (SomaScan ID:25464-1)

CYP2C9 · rs80159642

Omega-3 Fatty Acids to Polyunsaturated Fatty Acids percentage

CYP2C9 · rs9332238

Urine X-24354 levels in chronic kidney disease

CYP2C9 · rs111667734

Questions about Sulfonylureas

What are sulfonylureas?

Sulfonylureas — gliclazide, glimepiride, glibenclamide and tolbutamide — are among the oldest diabetes drugs still in wide use. A real pharmacogenomic effect here is one guidelines deliberately decline to act on, which is more useful to know than one they do act on.

Does a reduced-function CYP2C9 variant mean my sulfonylurea dose should change?

According to the Dutch Pharmacogenetics Working Group, no. Reduced-function CYP2C9 alleles slow the clearance of gliclazide, glimepiride and other sulfonylureas, so blood levels run higher — but the working group reviewed this and recommends no dose adjustment.

If sulfonylurea blood levels run higher with a CYP2C9 variant, doesn’t that raise the risk of low blood sugar?

A meta-analysis of 2,769 patients found no significant increase in sulfonylurea-induced hypoglycaemia for the CYP2C9*3 variant. Where drug levels do run higher, the added effectiveness appears to offset the added risk.

Quoting this page

Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.

Sulfonylureas. MyGeneLog™. https://www.mygenelog.com/drugs/sulfonylureas

This page is educational and contains no dosing information. Where a clinical guideline covers one of these gene-drug pairs it is written for prescribers and works through validated algorithms alongside clinical monitoring. Nothing here is a reason to start, stop, or change a medication — that conversation belongs with the clinician or pharmacist managing your treatment.