NutriStack
Glipizide and Milk Thistle, a caution.
Glipizide is metabolized primarily by CYP2C9. Silymarin (milk thistle) inhibits CYP2C9 in vitro and has independent hypoglycemic activity demonstrated in type 2 diabetes meta-analyses. The combination can raise glipizide exposure and amplify its glucose-lowering, producing hypoglycemia especially in older adults or after missed meals.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
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What the row says.
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At a glance
- Substances
- Glipizide and Milk Thistle
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. Glipizide is metabolized primarily by CYP2C9. Silymarin (milk thistle) inhibits CYP2C9 in vitro and has independent hypoglycemic activity demonstrated in type 2 diabetes meta-analyses. The combination can raise glipizide exposure and amplify its glucose-lowering, producing hypoglycemia especially in older adults or after missed meals.
Mechanism. Silymarin flavonolignans modestly inhibit CYP2C9, the primary enzyme that metabolizes glipizide, potentially raising plasma drug concentrations. Silymarin also independently improves insulin sensitivity and reduces oxidative stress in pancreatic islets, lowering glucose. Combined pharmacokinetic and pharmacodynamic effects increase hypoglycemia risk.
Recommendation. Tell your prescriber before adding milk thistle on glipizide. Monitor fingerstick glucose more often during the first 4 weeks and ask whether the glipizide dose should be reduced.
Sources (2)
- Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-1616. PMID 25028567
- Voroneanu L, Nistor I, Dumea R, Apetrii M, Covic A. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res. 2016;2016:5147468. PMID 27340676
Stack Score
How this pair moves the number.
Effect on the composite score
If both Glipizide and Milk Thistle are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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